peptide

Abstract

The present invention relates to peptides, and particularly, although not exclusively, to peptides isolated from the human gut microbiome which impact the gut-brain-axis in a subject. The invention extends to the use of these peptides in therapy, as well as novel compositions, therapies, and methods for treating, preventing, or ameliorating diseases caused by, or associated with, the gut-brain-axis.

Description

[0001]Peptide The present invention relates to peptides, and particularly, although not exclusively, to peptides isolated from the human gut microbiome which impact the gut-brain-axis in a subject. The invention extends to the use of these peptides in therapy, as well as novel compositions, therapies, and methods for treating, preventing, or ameliorating diseases caused by, or associated with, the gut-brain-axis. The human gut microbiome is central to human health, development, and disease. Gut microbes have the ability to modulate various key aspects of physiology and behaviour via the gut-brain-axis, a dynamic bidirectional signalling pathway linking the gut and the central nervous system via the peripheral nervous system, further including metabolic, immune, and endocrine mechanisms. Function of the gut-brain-axis facilitates the fundamental physiological processes of normal digestion, including intestinal motility, blood flow, and satiety, hormone secretion, including GPCR stimulation (e.g. TGR5, GPR40, GPR119, SSTR5, CCKa), fat metabolism and glucose regulation. The gut- brain-axis is, therefore, central to ensuring the maintenance of gut homeostasis, and, in the same manner, is inextricably linked to disease. A multitude of diseases have been linked to the gut-brain-axis; these include neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease and dementia; central nervous system disorders, such as mood disorders, anxiety and depression; metabolic diseases, such as diabetes and obesity; autoimmune and inflammatory disorders, such as inflammatory bowel disease; gut barrier dysfunction, such as environmental enteric dysfunction; and functional gastrointestinal disorders, such as irritable bowel syndrome. Human small proteins, such as peptide neurotransmitters, play important roles in the gut-brain-axis. For example, cholecystokinin (CCK) peptides act through CCK-1 receptors in the gall bladder, pancreas, stomach, and brain to stimulate bile flow and digestion, to delay gastric emptying and to induce satiety. Further examples include peptide YY and GLP-1, both of which are secreted by L-cells and, too, have roles in satiation. Proteins derived from bacteria can mimic human peptide neurotransmitters and peptide hormones. For example, E. coli protein ClpB contains an α-melanocyte- stimulating hormone (α-MSH)-like motif (Tennoune et al., 2014), which can bind melanocortin receptors (Ericson et al., 2015) and gain the ability to enter the bloodstream and activate neurons (Breton et al., 2016). Bacterial toxins, such as the Clostridial neurotoxins Botulinum toxin and tetanus toxin, are also capable of interrupting nervous system function. There is, therefore, the need for a new therapeutic treatment of conditions that are caused by, or are associated with, the gut-brain-axis, that harnesses the ability of small proteins and / or peptides to impact the gut-brain-axis, which is sometimes called the microbiome gut-brain-axis. The inventors investigated a set of peptides found in human gut microbiome samples from healthy human subjects. Through the use of a known behavioural screen in C. elegans, the inventors unexpectedly identified 66 peptides that had impacts on the gut-brain-axis. The investigation was based on the premise that recent bioinformatic advances have prompted the postulation of the existence of thousands of bacterial peptides or small proteins in metagenomic samples, that would have previously not been annotated due to their small size (Sberro et al., 2019). As a model organism, C. elegans has long been known to those skilled in the art to constitute an effective and powerful tool in recapitulating numerous phenotypes associated with human disease, particularly in phenotypes that are associated with neural function and behaviour. This utility stems from the fact that C. elegans shares many conserved biological pathways with humans, including peptide signalling mechanisms between the gut and the nervous system. Furthermore, the high level of homology between C. elegans and human genomes, wherein C. elegans carries homologues for 60-80% of human genes, demonstrates C. elegans as an appropriate model for the study of human disorders and diseases. Of these homologous genes, included are those encoding various neural signalling pathways, such as serotonergic and GABAergic signalling, and it is known to the skilled technician that worm behaviours are linked to neuronal function. Indeed, there is a large body of literature which shows that worm behaviours are linked to neuronal function, and that findings in C. elegans concerning such signalling pathways are readily translatable to a wide range of human conditions. For example, it has been previously shown that the same C. elegans behavioural assays described herein can be used to detect the effect of mutations associated with diverse genetic diseases in humans (O’Brien et al., 2023). Another recent study evidenced that peptide signals from the gut impact neural function and behaviour in worms. For example, it has been shown that gamma-aminobutyric acid (GABA) inhibits, while acetylcholine (ACh) promotes, the systemic mitochondrial unfolded protein response (UPRmt) in the intestine of C. elegans (Cornell et al., 2024). It has also been shown that a neuropeptide-like protein (NLP-40) carries timing information from pacemakers to GABAergic neurons by instructing their activation, and it has therefore been suggested that rhythmic release of neuropeptides can deliver temporal information from pacemakers to downstream neurons to execute rhythmic behaviours (Wang et al., 2013). In addition, the recently discovered peptide, INS-7, which is secreted in the intestine in response to food withdrawal, functions as a gut-to-brain peptide by attenuating the release of a neuropeptide that drives fat loss (Liu et al., 2024). Furthermore, it has also been shown that intestinal signalling to GABAergic neurons regulates a rhythmic behaviour, namely the defecation motor program (DMP), in C. elegans (Mahoney et al., 2008). Yet another example of the value of C. elegans as a means of modelling complex human diseases is provided by a group who recently discovered a hit in a C. elegans repurposing screen that was utilised as part of an N-of-1 human trial (Iyer et al., 2019). Critically, this hit is, at the present time, being investigated in a pivotal phase II / III clinical trial (National Clinical Trial number: NCT04925960). A further repurposing study includes a C. elegans screen which identified a class of neuroleptics that restored motility in these worms, the most potent of which was pimozide. Indeed, this molecule was tested in a phase II clinical trial in human subjects with amyotrophic lateral sclerosis (ALS), the results of which identified pimozide as a promising ALS therapeutic in human (Patten et al., 2017). A whole-animal behavioural screen in C. elegans is therefore highly suitable for enabling holistic testing across various gut-brain-axis mechanisms, the results of which may be readily translated to human, as supported by the above described studies. Accordingly, the inventors believe that any one of this set of 66 peptides (SEQ ID No: 1-66), or their corresponding truncated mature peptides, or their corresponding encoding nucleic acids, may be utilised as a therapeutic agent to treat, prevent, or ameliorate a disease caused by, or associated with, the gut- brain-axis. Thus, according to a first aspect of the invention, there is provided a peptide comprising an amino acid sequence substantially as set out as SEQ ID No: 38, 33, 59, 58, 43, 1-32, 34-37, 39-42, 44-57, 60-66, or a variant or fragment thereof, or a nucleic acid encoding one or more of the peptide, or a variant or fragment thereof, for use in therapy. The inventors believe that the peptides described herein, or a corresponding encoding nucleic acid, can be used to treat conditions caused by, or associated with, the human gut-brain-axis. Hence, according to a second aspect, there is provided a peptide comprising an amino acid sequence substantially as set out as SEQ ID No: 38, 33, 59, 58, 43, 1-32, 34-37, 39-42, 44-57, 60-66, or a variant or fragment thereof, or a nucleic acid encoding one or more of the peptide, or a variant or fragment thereof, for use in treating, preventing, or ameliorating a disease caused by, or associated with, the gut-brain-axis. In accordance with a third aspect, there is provided a method of treating, preventing, or ameliorating a disease caused by, or associated with, the gut- brain-axis, the method comprising, administering or having administered, to a subject in need of such treatment, a therapeutically effective amount of a peptide comprising an amino acid sequence substantially as set out as SEQ ID No: 38, 33, 59, 58, 43, 1-32, 34-37, 39-42, 44-57, 60-66, or a variant or fragment thereof, or a nucleic acid encoding one or more of the peptide, or a variant or fragment thereof. As described in the Examples, the inventors were surprised to isolate 66 peptides which, using the established behavioural screen in C. elegans, are believed to have an impact on the gut-brain-axis in human subjects, and can therefore be used in therapy. Accordingly, the peptides or their encoding nucleic acids may be used to treat a condition that is directly linked to (i.e. caused by) the gut-brain axis, or indirectly linked to (i.e. associated with) the gut-brain axis. Anatomical target sites of the peptide comprising an amino acid sequence substantially as set out as SEQ ID No: 1-66, or a variant or fragment thereof, or a nucleic acid encoding one or more of the peptide, or a variant or fragment thereof, may be selected from a group of target sites consisting of: the gastrointestinal tract (including enteroendocrine cells, immune cells, epithelial cells, enteric neurons, smooth muscle cells, interstitial cells of Cajal, enterochromaffin cells); the peripheral nervous system (including dorsal root ganglia, sympathetic and parasympathetic arms of the autonomic nervous system, enteric nervous system, or vagus nerve); the central nervous system; the neuroendocrine system; the neuroimmune system; the hypothalamic- pituitary-adrenal axis; and the gut microbiota. The disease may entail an effect on general physiological and / or homeostatic roles, which may be selected from a group of roles consisting of: satiety; food intake; glucose regulation; fat metabolism; insulin secretion; intestinal motility; blood flow; secretion and absorption by the gut; normal digestion; hormone secretion; GPCR stimulation (e.g. TGR5, GPR40, GPR119, SSTR5, CCKa, PDE4, or DPP-4); release of neurotransmitters (e.g. GLP-1, GLP2, GIP, PYY, or CCK); metabolic and oxidative stress; inflammation (e.g., via vagus nerve); stimulation of autoantigens; mood; fear; temperament; cognition; memory; sociability; and aging. The disease to be treated by the peptide comprising an amino acid sequence substantially as set out as SEQ ID No: 1-66, or a variant or fragment thereof, or a nucleic acid encoding one or more of the peptide, or a variant or fragment thereof, may be selected from a group of diseases caused by, or associated with, the gut-brain-axis, consisting of: neurodegenerative diseases; central nervous system disorders; metabolic disorders; autoimmune and inflammatory disorders; gut barrier dysfunction; and functional gastrointestinal disorders. The neurodegenerative disease may be selected from a group of neurodegenerative diseases consisting of: Alzheimer's disease (including Benson's syndrome); Parkinson's disease (including progressive supranuclear palsy, Steele-Richardson-Olszewski syndrome, normal pressure hydrocephalus, vascular or arteriosclerotic parkinsonism, or drug-induced parkinsonism); dementia (including Lewy Body dementia, vascular dementia, or frontotemporal dementia); episodic cluster headache; migraine; pain; multiple sclerosis; Huntington's disease; amyotrophic lateral sclerosis; Lou Gehrig's disease; motor neuron disease; prion disease; spinocerebellar ataxia; spinal muscular atrophy; primary progressive aphasia; mild cognitive impairment; HIV-related cognitive impairment; progressive inflammatory neuropathy; and corticobasal degeneration. Preferably, the neurodegenerative disease is selected from a group of neurodegenerative diseases consisting of: Alzheimer's disease; Parkinson's disease; dementia; and multiple sclerosis. The central nervous system disorder may be selected from a group of central nervous system disorders consisting of: mood disorders; anxiety; depression; affective disorders; schizophrenia; malaise; cognition disorders; addiction; autism; and epilepsy. Preferably, the central nervous system disorder is selected from a group of central nervous system disorders consisting of: mood disorders; anxiety; depression; and autism. The metabolic disorder may be selected from a group of metabolic disorders consisting of: diabetes (and complications, such as diabetic nephropathy, diabetic retinopathy, or diabetic neuropathy); cardiovascular disease; metabolic syndrome; obesity; dyslipidaemia; non-alcoholic fatty liver disease and non- alcoholic steatohepatitis. Preferably, the metabolic disorder is selected from a group of metabolic disorders consisting of: diabetes; obesity; non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. The nutritional disorder may be selected from a group of nutritional disorders consisting of: hyperphagia; cachexia; anorexia nervosa; short bowel syndrome; intestinal failure; intestinal insufficiency; and eating disorders. Preferably, the nutritional disorder is hyperphagia or cachexia. The inflammatory and / or autoimmune disorder may be selected from a group of inflammatory and / or autoimmune disorders consisting of: inflammatory bowel disease; ulcerative colitis; Crohn's disease; psoriasis; coeliac disease; and arthritis. Preferably, the inflammatory and / or autoimmune disorder is inflammatory bowel disease. The gut barrier dysfunction may be selected from a group of gut barrier dysfunctions consisting of: environmental enteric dysfunction; and spontaneous bacterial peritonitis. The functional gastrointestinal disorder may be selected from a group of functional gastrointestinal disorders consisting of: irritable bowel syndrome; functional dyspepsia; functional abdominal bloating / distension; functional diarrhoea; functional constipation; and opioids-induced constipation. Preferably, the functional is irritable bowel syndrome; and functional dyspepsia. The disease may be selected from a group of other diseases consisting of: 5 enteritis (chemotherapy-induced, radiation-induced); necrotising enterocolitis; gastrointestinal injury (toxic, radiation, chemotherapy); gastroparesis; nausea; and vomiting. Preferably, the disease is enteritis. 10 The peptide may comprise an amino acid sequence provided herein as SEQ ID No: 1-66, and a corresponding nucleic acid sequence provided herein as SEQ ID No: 67-132, as shown in Table 1. It will be appreciated that the DNA sequences used to encode the peptides described herein are not found in nature. Indeed, 15 they were codon optimised by the inventors to suit expression in the E. coli strain used for delivery to C. elegans worms. Table 1: Amino acid and corresponding nucleic acid sequences for SEQ ID No: 1- 187 and corresponding originating bacteria 20 SEQ Amino acid SEQ Predicted SEQ Nucleic acid Originating bacteria ID: sequence ID: mature ID: sequence peptide sequence1MAFLGWFVHYV67ATGGCCTTCTTAGGGTGG Roseburia hominis LIMVILAAVAV TTTGTTCACTATGTTCTG AGVFAGRKWAE ATTATGGTGATTCTTGCA KSKAKKDTAAS GCAGTTGCTGTAGCGGGG GNAGKE GTATTCGCCGGTCGTAAG TGGGCAGAAAAATCGAAG GCCAAAAAAGACACGGCA GCTTCTGGCAATGCAGGA AAGGAG2MSLTGWLTMIF68ATGTCGTTGACCGGGTGG Akkermansia; SISGVLTAAVW CTGACTATGATCTTTAGC Akkermansia sp. CAG:344 AYYKVLSTPRE ATTTCAGGCGTCCTGACG TEHLLSPTPPL GCTGCGGTGTGGGCTTAT PEDPDQ TATAAGGTACTTAGTACA CCGCGCGAAACCGAACAT CTTTTGTCTCCAACCCCC CCTTTACCTGAAGACCCA GACCAG MNNRIRNNKKS133(AQGNGLA)GI69Bacteroides fragilis 3_1_12; ILTVALIVAAT NEATSMVTSYF AATAATAAAAAATCAATT Bacteroides sp.14(A) ASAFAQGNGLA DPGV CTTACCGTGGCGCTGATT GINEATSMVTS GTCGCAGCGACGGCATCT YFDPGV GCTTTCGCCCAGGGAAAC GGTCTTGCGGGAATCAAT GAGGCTACGAGCATGGTG ACGAGCTACTTTGACCCT GGTGTC MSFLRRNLWAC134(A)ETVLRKAI70ATGTCGTTCCTTCGTCGT Flavonifractor sp. An10 ALLLTGAVFVG TICMECIGLG AATCTGTGGGCTTGCGCC LGAWRGEAETV CTGTTACTGACGGGAGCA LRKAITICMEC GTCTTCGTTGGCTTGGGC IGLG GCATGGCGCGGCGAGGCT GAAACGGTATTGCGTAAA GCCATTACTATTTGCATG GAATGTATCGGACTTGGA MKKILLLTGLL135FIYEDTCLDLG71ATGAAGAAGATTTTACTT Neisseria sp. HMSC056A03; IAAFYAGMKVQ GGKNPGYPICV TTGACCGGGCTTCTTATT Neisseria sp. HMSC065C04; AFIYEDTCLDL VEK GCTGCTTTCTATGCAGGA Neisseria mucosa C102; GGGKNPGNYPI ATGAAAGTGCAGGCATTC Neisseria subflava NJ9703; CVVEK ATCTATGAAGATACGTGT CTGGACTTGGGAGGCGGA Neisseria; AAAAACCCAGGTAACTAC Neisseria sp. HMSC073G10; CCAATTTGTGTAGTTGAG Neisseria sp. HMSC072B12; AAA Neisseria sp. HMSC15G01; Neisseria sp. HMSC070H10; Neisseria sp. oral taxon 014 str. F0314; Neisseria sp. HMSC068C12; Neisseria sp. HMSC063B05; Neisseria sp. HMSC075C10; Neisseria polysaccharea NS342; Neisseria flavescens SK114; Neisseria sp. HMSC061H08; Neisseria sp. HMSC064D07; Neisseria sp. HMSC069H12; Neisseria sp. HMSC072C05; Neisseria sp. HMSC064F04; Neisseria sp. HMSC056A04; Neisseria sp. HMSC058F07; Neisseria elongata subsp. elongata; Neisseria sp. HMSC078C12; Neisseria sp. HMSC075C12; Neisseria sp. HMSC068C04; Neisseria sp. HMSC061B04; Neisseria sp. HMSC066H01; Neisseria flavescens NRL30031 / H210; Neisseria sp. HMSC071A01; Neisseria sp. HMSC073B07; Neisseria sp. HMSC064F03; MASIIVVVIIF136(ILFI)CQNGG 72ATGGCATCAATTATCGTT Gemmiger formicilis; VLLALAILFIC WQGGCGGNCAG GTGGTCATTATTTTCGTA Faecalibacterium sp. UBA1360; QNGGWQGGCGG TTACTTGCCCTGGCAATT Ruminococcaceae; NCAGCHNKCAD CHNKCADADKK Faecalibacterium sp. UBA2087; ADKKKK KK GGCGGGTGGCAGGGAGGT Subdoligranulum variabile DSM TGCGGGGGGAATTGTGCT 15176; GGGTGCCACAATAAGTGC GCCGACGCGGATAAGAAA AAAAAA MAGSKKKNIAA137(AA)DSRCMYC73ATGGCTGGCAGCAAAAAA Roseburia hominis A2-183; TILGKVALNSA LHQPKQPAGIK AAGAATATCGCTGCGACT Roseburia faecis; KAAADSRCMYC KLFR ATTCTGGGAAAGGTTGCT LHQPKQPAGIK CTGAACAGTGCAAAGGCG KLFR GCGGCTGACAGTCGTTGT ATGTATTGTCTTCATCAG CCCAAGCAACCGGCTGGT ATTAAGAAGTTGTTCCGT MKKRSIISLAL138(EANA)VMQKA74ATGAAGAAACGTAGTATC Lachnospiraceae bacterium LAAGLAFIVIG IMICMECIGLG ATCAGCTTGGCCCTTCTT UBA2734; AVRGEANAVMQ GCAGCCGGCCTTGCTTTC unclassified Lachnospiraceae; KAIMICMECIG ATCGTAATTGGAGCAGTG Unclassified; LG CGCGGTGAAGCCAACGCA GTCATGCAGAAGGCTATT Janthinobacterium sp.13; ATGATCTGCATGGAGTGT Clostridiales bacterium 52_15; ATCGGCCTGGGT Terrabacteria group; uncultured Flavonifractor sp.; [Eubacterium] siraeum DSM 15702; Faecalibacterium sp. UBA2087; MKHVKTLNNAM139CGECQTSCQSA75ATGAAGCATGTGAAGACC Lachnospiraceae bacterium LKESLVKGGCG CKTSCTVANQP TTGAACAACGCAATGCTT UBA3820; ECQTSCQSACK CENR AAAGAGTCATTAGTGAAA Peptococcaceae bacterium TSCTVANQPCE GGCGGTTGTGGCGAATGC UBA5757; NR CAGACTTCGTGCCAAAGC GCGTGCAAGACCAGTTGT ACCGTGGCTAATCAACCA TGTGAGAACCGT MNTADWIVVIL140ISISKQKKKGK76ATGAACACAGCGGACTGG Ruminococcus sp. N15.MGS-57; LLLWAVAAAIS CCGCCSHCHSR ATTGTCGTAATCCTGCTT Ruminococcus bicirculans; ISKQKKKGKCC CGKK CTGCTGTGGGCCGTCGCG GCCSHCHSRCG GCTGCAATCTCTATCAGT KK AAACAGAAGAAGAAAGGC AAGTGTTGCGGATGCTGT TCCCATTGTCATAGTCGC TGTGGCAAGAAG MGLKHLFGWGI141CGSACGAGDPK77ATGGGCTTAAAGCACTTA Intestinimonas butyriciproducens; KAESKAATACG PTACGSACGAG TTCGGATGGGGCATTAAG SACGAGDPKPT DKQ GCCGAGTCCAAAGCTGCC ACGSACGAGDK ACAGCGTGCGGATCAGCC Q TGTGGAGCGGGAGATCCC AAGCCTACAGCTTGCGGG AGCGCCTGTGGGGCTGGA GATAAGCAAMLGFIIGLFLG142(CSVTSKA)DE78ATGTTAGGCTTCATTATT Candidatus Gastranaerophilales AFIGVAVMCLC DTENYKYAKEN GGATTGTTTCTGGGTGCT bacterium HUM_10; SVTSKADEDTE KKDE TTCATTGGGGTTGCAGTT Ruminococcus bromii; NYKYAKENKKD ATGTGTTTGTGCTCAGTA Candidatus Gastranaerophilales E ACGTCTAAAGCTGACGAA GATACAGAAAATTACAAG bacterium HUM_11; Eubacterium sp. CAG:202; AAGGACGAGMTRFTFIKTLV143YIERDTNGNAK79ATGACACGCTTTACCTTC Prevotella pallens ATCC 700821; ISMLLKGNGYA ALHYIPAELVT ATCAAAACGTTAGTTATT Prevotella sp. ICM33; YIERDTNGNAK VI TCAATGTTGTTGAAAGGC ALHYIPAELVT AATGGTTATGCTTACATT VI GAGCGTGACACTAATGGG AATGCTAAGGCCCTTCAT TATATTCCGGCTGAGTTA GTTACCGTCATCMILYHGTTVDI144KGFFAYSVYIG80ATGATCCTTTATCATGGA Bacteroides sp.14(A); KEIDLQKSKPN YVCKIAGC ACCACTGTAGACATCAAG Bacteroides cellulosilyticus WH2; KDFGKGFFAYS GAGATCGACTTACAAAAA Bacteroides cellulosilyticus DSM VYIGYVCKIAG TCGAAACCTAACAAGGAC 14838; C TTTGGCAAGGGTTTCTTT GCATATAGTGTGTATATC Bacteroides sp. CAG:20; GGGTACGTGTGCAAGATC GCAGGTTGT MKQSVKKITLG145DNINNESNSIS81ATGAAACAGAGTGTAAAG Clostridiales bacterium 52_15; TAALYCRLSRG NHDRKQITIFN AAAATTACATTGGGCACG DNINNESNSIS DP GCGGCATTATACTGCCGC NHDRKQITIFN TTGTCGCGCGGGGATAAC DP ATCAACAACGAATCCAAC TCAATTTCCAACCACGAC CGCAAACAAATCACGATC TTCAACGACCCAMKKLVTCCVAV146(GIVVRQVLL)82ATGAAAAAATTGGTTACC Actinomyces sp. oral taxon 172 str. GSVVAVGIVVR DLSDNADLWMS TGTTGTGTAGCGGTAGGC F0311; QVLLDLSDNAD VTDVVED TCTGTTGTTGCTGTCGGT Actinomyces sp. Marseille-P2825; LWMSVTDVVED ATCGTAGTTCGTCAAGTG Actinomyces graevenitzii F0530; TTGCTGGATTTGTCCGAC AACGCTGACTTGTGGATG Actinomyces sp. ICM47; TCAGTAACGGACGTGGTT GAAGATMSLRNVFCGGN147NNGCGCGCGC83ATGAGCCTGCGCAACGTCUnclassified; SCTWILFVIII TTCTGCGGGGGTAATTCA Bacteria; LLILDDDDCGC TGCACATGGATTCTGTTT GANNGCGCGCG GTCATTATCATCCTTTTG C ATTTTAGACGACGACGAC TGCGGGTGCGGGGCAAAT AACGGGTGTGGTTGCGGA TGTGGGTGT MKTQKSNLQKG84ATGAAAACTCAGAAGTCC Butyricimonas virosa DSM 23226 NKNTQNHVSLS AACCTTCAAAAGGGTAAT KGSSKKTSTKK AAGAATACTCAAAATCAC VSKFNFKHGTF GTATCCTTGAGTAAGGGG C AGTTCAAAAAAGACCAGT ACCAAAAAGGTTTCCAAG TTCAACTTCAAACATGGC ACTTTTTGC MKFVKGLMVGS148(WT)DNDMTTK85ATGAAGTTCGTCAAGGGC Clostridium sp. CAG:356; LITTGVIMAWT KITKKGKKWAR TTAATGGTTGGATCTCTT Clostridium sp.28_12; DNDMTTKKITK KMGMI ATCACTACCGGCGTTATT KGKKWARKMGM ATGGCCTGGACAGATAAC I GACATGACCACAAAAAAG ATTACAAAGAAAGGAAAA GGGATGATTMGTVIVLVVLV149(MVKG)KKNGK86ATGGGAACTGTGATTGTT Firmicutes VIVAAIVHTMV HSCGGDCGHCG CTTGTTGTTTTAGTGGTT KGKKNGKHSCG GCH ATCGTTGCCGCTATTGTG GDCGHCGGCH CATACTATGGTCAAGGGA AAGAAGAACGGTAAGCAT TCGTGCGGCGGAGACTGC GGGCATTGCGGTGGGTGT CACMNRKKREFAVA150LRIMKKVDEKL87ATGAATCGTAAAAAGCGC Oscillospiraceae bacterium Zagget4; LALLSASSALC RREKEKRTRK GAGTTTGCAGTTGCACTT Firmicutes bacterium LRIMKKVDEKL GCTCTGCTGTCCGCATCA CAG:176_63_11; RREKEKRTRK AGCGCGTTGTGTCTTCGT ATTATGAAAAAGGTGGAC GAGAAACTTCGTCGCGAA AAGGAAAAGCGCACCCGC AAA MSLKDSMIRGL151NSQMILDIIND88ATGTCATTGAAGGACAGC Bifidobacterium longum subsp. suis AMYGATSLAQS TDKNAR ATGATTCGTGGTCTTGCT GHANSQMILDI ATGTATGGGGCTACGTCG INDTDKNAR TTGGCTCAAAGTGGACAT GCTAATTCTCAGATGATT CTTGATATTATTAACGAC ACAGATAAAAATGCCCGCMRSKRIIIFLL152(KEHKTVFTKA89ATGCGCTCTAAACGCATT Phascolarctobacterium SATFLIYGLFG )ATICLECIGI ATTATTTTCCTTTTAAGT succinatutens; KEHKTVFTKAA G GCGACATTTTTGATCTAT Phascolarctobacterium TICLECIGIG GGGCTGTTCGGAAAAGAG succinatutens YIT 12067; CACAAAACTGTTTTTACT AAAGCTGCCACGATTTGT Phascolarctobacterium CTGGAATGTATTGGAATC succinatutens CAG:287; GGG MNRGKRFPIKG153VNLNNHIAA90ATGAATCGTGGGAAGCGT Prevotella melaninogenica D18; KKIMISVVLSA TTCCCCATTAAGGGGAAG Prevotella melaninogenica; VVVAALVAKAV AAAATTATGATTTCTGTC Prevotella sp. ICM33; NLNNHIAA GTCTTAAGTGCGGTAGTT Prevotella melaninogenica ATCC GTCGCAGCATTAGTTGCG AAAGCAGTTAATTTGAAC 25845; AACCATATTGCAGCGMMGVIAAVAGA154LLDAIEKPSVP91ATGATGGGGGTGATTGCC Clostridiales bacterium 42_27; IQIASWAMALL TPTKARHREP GCTGTCGCGGGAGCTATC DAIEKPSVPTP CAAATCGCCTCTTGGGCA TKARHREP ATGGCTTTGCTTGATGCT ATCGAAAAACCGTCGGTA CCAACCCCGACGAAAGCC CGCCACCGTGAGCCT MLGFIIGLFIG155DEQMKDNIDDK92ATGTTAGGTTTTATCATC Clostridiales bacterium 42_27 VFIGVCIMCLC K GGCCTGTTCATCGGCGTT NAAAKADEQMK TTTATTGGGGTTTGTATC DNIDDKK ATGTGTCTGTGCAATGCA GCGGCAAAGGCAGATGAG CAGATGAAAGATAACATC GACGATAAAAAGMKPNGYYTWSA156YWQFESEEDYL93ATGAAACCAAATGGGTAT uncultured Coprococcus sp. YMGFVPSANAY NYLKERGEI TATACATGGAGTGCCTAC ATGGGTTTTGTCCCATCC WQFESEEDYLN YLKERGEI TTTGAGTCCGAAGAAGAT TACCTTAACTATTTAAAG GAGCGCGGTGAGATT MSFMLFIGPII94ATGTCTTTCATGTTGTTC [Eubacterium] eligens; GVAVAIIAAVV ATTGGACCAATCATTGGG [Eubacterium] eligens; IISVVAAAVAQ GTAGCGGTAGCGATTATC Roseburia hominis A2-183; KDINDED GCGGCTGTCGTCATCATT Clostridium sp. CAG:127; TCGGTAGTCGCCGCAGCA GTTGCTCAGAAGGATATT Roseburia intestinalis XB6B4; AACGACGAAGAT [Eubacterium] eligens ATCC 27750;MKKFRIKKKTA157(A95ATGAAGAAATTCCGCATC uncultured Flavonifractor sp. HKINIAVLPRKAIR)IKCIGILAPLA V AAAAAGAAAACTGCCATC AAAIIVPKAIR AAGTGCATCGGTATTCTT HKNALRV GCTCCGCTGGCCGCCGCT GCTATCATCGTACCCAAA GCTATCCGCCACAAAAAC GCGCTGCGTGTG MELLMWSAYFF158ASDLCKLRIVS 96 Clostridiales; AAVFVVNVALE KTR DLCKL ATGGAACTG Lachnospiraceae; AISAAS TTGATGTGG TCTGCGTACT Unclassified; RIVSKTR TCTTCGCT GCCGTCTTTGTAGTGAAT Firmicutes bacterium CAG:882; GTAGCTTTAGAGGCGATC Akkermansia muciniphila ATCC BAA- AGCGCGGCATCTGATCTG 835; TGCAAACTGCGTATTGTG Clostridium sp. CAG:91; AGTAAAACCCGT MLGFIIGLIIG159(CITAGQA)DK97ATGCTGGGTTTTATCATT Clostridiales bacterium 36_14; GTVGVFAMALC RENCTDSDK GGCTTAATTATTGGAGGG Ruminococcus bicirculans; ITAGQADKREN ACAGTAGGAGTCTTCGCA CTDSDK ATGGCCTTATGTATTACT GCCGGACAGGCGGACAAA CGCGAAAATTGCACAGAC AGCGATAAGMMNLWSAIASF160(ANLGAG98ATGATGAACTTATGGTCG Clostridiales bacterium 52_15 NGMSYEPAE)LAPSIEAFANLGAGA E GCTATCGCATCATTCATT ASNGMSYEPEL ELRK GAAGCCTTCGCTAACCTT PEELRK GGAGCCGGAGCAGCAAGC AATGGCATGTCATACGAA CCCGAATTACCGGAGGAA CTTCGCAAGMIIYLISLLVI161(99ATGATTATTTATTTAATT Bacteroides clarus CAG:160; GSAIAWSLKKA TWESL)WLGKAKDAEPQSEDK TCCCTTCTTGTAATCGGA PSDTELWGADE E AGCGCCATCGCGTGGTCA QEKE CTTAAAAAAGCGCCGTCA GATACTGAATTGTGGGGT GCGGATGAGCAGGAGAAA GAG MKKKIMITIAS162GYLHFSGKMPF100ATGAAGAAGAAAATTATG Clostridiales MAARGAAVAGY GHSHFR ATTACGATTGCCTCTATG LHFSGKMPFGH GCAGCGCGTGGTGCCGCA SHFR GTCGCGGGTTATTTGCAC TTCAGCGGAAAGATGCCG TTTGGACACAGCCACTTC CGCMLWFIIGLLLG163(101ATGCTTTGGTTTATCATC Ruminococcus ECMNEAT)KAIKKNADEGTMGAAVMALC GGGCTGCTGTTGGGGGGT NAAKNADEEME TKIK ATGGCGCTGTGCAATGCA GCAAAAAACGCGGATGAG GAGATGGAAACCAAGATC AAGMLPLFAAAAAA164AG102ATGCTGCCATTATTTGCA Veillonella sp.6_1_27; AVVKLSLGVSVYQAAWEGFAAGVL DD GCCGCTGCAGCGGCTGCT Veillonella parvula DSM 2008; LGVSVYQAVKS GCATGGGAAGGCTTCGCC Veillonella; DD GCTGGTGTTTTATTAGGT Veillonella sp.3_1_44; GTATCGGTTTATCAGGCC GTTAAAAGTGACGATMKELIKLAAAS165(103ATGAAGGAATTGATTAAG Neisseria macacae ATCC 33926; ATIHKIA)DNMRTLIGMSGLTAGA K TTGGCGGCTGCATCATTG Neisseria sp. HMSC055H02; THIADNMRTAI ATTGGAATGTCGGGGCTG Neisseria; KK ACTGCGGGAGCTACGCAT Neisseria sp. HMSC70E02; ATCGCAGATAACATGCGC ACCGCAATCAAAAAA Neisseria elongata subsp. elongata; Neisseria sicca DS1; Neisseria sp. HMSC065D04; Neisseria sicca ATCC 29256; Neisseria sicca VK64; Neisseria sp. oral taxon 014 str. F0314; Neisseria sp. HMSC072F04; Neisseria sp. HMSC03D10; Neisseria meningitidis; Neisseria sp. HMSC064F04; Neisseria sp. HMSC067H09; Neisseria sp. HMSC074B07; Neisseria sicca 4320; Selenomonas noxia ATCC 43541; Neisseria sp. HMSC064D07; Neisseria sp. HMSC077D05; Neisseria elongata subsp. glycolytica ATCC 29315; Neisseria sp. HMSC070E12; Neisseria sp. GT4A_CT1; MDGLMFIFSLG166IWLNTKSGQKW104ATGGACGGTTTAATGTTC Prevotella copri CAG:164 LIISSSFAIWL IDNL ATCTTTTCGCTGGGCTTA NTKSGQKWIDN ATTATTTCTTCATCGTTT L GCGATTTGGCTGAACACT AAGAGCGGCCAGAAGTGG ATTGATAATTTA MTIFPGLAIAV167DGLRDALDPKL105ATGACCATCTTTCCCGGA Xenorhabdus innexi TIFSLNALGDG RD TTGGCTATTGCAGTAACA LRDALDPKLRD ATCTTTTCCTTGAACGCG CTTGGAGATGGCTTACGC GACGCTCTTGACCCAAAG TTGCGCGACMKKSVWKQILQ HI106ATGAAGAAAAGCGTATGGBacteroides caccae ATCC 43185; IFITVATSIIS AAACAGATCCTTCAAATC Bacteroides ovatus CL03T12C18; ALGVTSGVAHI TTTATCACGGTGGCTACC Bacteroides finegoldii DSM 17565; TCAATCATCTCCGCGTTG Bacteroides stercoris CC31F; GGTGTGACATCTGGAGTG GCTCACATT Bacteroides sp.1_1_6; Bacteroides caccae CL03T12C61;MEMLSSFILSV168(HC)IGKWL107ATGGAAATGTTGTCTTCG Faecalibacterium prausnitzii L2-6 VAHCIGK QFKADEAANV GKH TTCATCTTGTCCGTTGCG WLDEQFKAGKH GCGAATGTTGTAGCTCAC TGTATCGGGAAGTGGCTT GACGAACAGTTCAAGGCC GGGAAGCATMKGYFVSGGYM108ATGAAGGGATACTTCGTTFirmicutes bacterium CAG:83 GLVGGSYQLFA TCAGGCGGATACATGGGT TESDYLEYLAD TTGGTTGGTGGCTCATAC CAGTTGTTTGCGACCGAG TCCGACTACTTAGAATAC TTGGCCGATMKKIMLSLLSY169(109ATGAAGAAAATCATGTTA Clostridiales bacterium 45_37 YLKVEGGAAVLS)TLATMSGLCLV TCGCTGCTGTCCTACACT GGAAVLSYKE CTTGCGACGATGTCAGGA CTGTGTCTTGTGGGAGGA GCAGCAGTGCTGTCCTAT AAGGAG MLYVIWVVGVL170(KLTIG)KEKS110ATGCTGTACGTCATTTGG Haemophilus parainfluenzae ATCC AAVMVSAKLTI GKFDE GTTGTTGGGGTCCTTGCG 33392; GKEKSGKFDE GCGGTGATGGTTTCGGCC Haemophilus sp. CCUG 60358; AAGTTGACTATTGGTAAA Haemophilus parainfluenzae T3T1; GAAAAGTCGGGTAAGTTT GACGAG Haemophilus sp. HMSC068C11; Haemophilus; Haemophilus sp. HMSC61B11; Haemophilus sp. HMSC71H05; Haemophilus sp. HMSC061E01; Haemophilus parahaemolyticus HK385; Haemophilus parainfluenzae HK2019; Haemophilus pittmaniae; Aggregatibacter sp. oral taxon 458 str. W10330; Neisseria subflava NJ9703; Haemophilus parainfluenzae HK262; Haemophilus sp. HMSC073C03;MCTYLAMLALG171(111ATGTGTACCTATCTTGCG Ruthenibacterium lactatiformans G GAAGLLA)ERKFALGAAFTAA ARR ATGTTGGCATTAGGCTTT LLAERKGARR GCATTAGGCGCTGCGTTC ACGGCTGCTGGTCTTCTG GCAGAACGTAAGGGCGCA CGCCGC MILKLGIFLVA112ATGATCTTAAAGCTGGGT Lachnoclostridium sp. An196; VGLVKLLVALA ATCTTCCTTGTGGCAGTG Clostridium sp.7_3_54FAA; MRAKEKRGKE GGGTTAGTAAAATTACTT GTCGCGTTGGCGATGCGT GCAAAAGAAAAACGCGGC AAAGAG MIIGFLSGLFI172AKERDDL113ATGATTATTGGATTCTTG butyrate-producing bacterium GSVAGATVMTL TCGGGACTTTTTATTGGT SSC / 2; CYAAKERDDL TCAGTTGCAGGTGCTACA Clostridiales bacterium GTAATGACATTATGCTAC 41_12_two_minus; GACCTGMSMKKTWSIILANL114ATGAGCATGAAGAAGACG Bacteroides uniformis CAG:3; KVIIAVAGAIA TGGAGCATCATTCTTAAA Bacteroides; GVVGVQAANL GTTATCATCGCAGTAGCG Bacteroides ovatus CL02T12C04; GGTGCCATTGCGGGTGTG Bacteroides sp.3_1_13; GTCGGCGTGCAAGCAGCC AACTTA Bacteroides ovatus 3_8_47FAA; Bacteroides sp. D22; Bacteroides xylanisolvens CL03T12C04; Bacteroides sp. KFT8; Bacteroides stercoris CC31F; Bacteroides dorei CL03T12C01; Bacteroides caccae CL03T12C61; Bacteroides sp. D2; Bacteroides fragilis JCM 11017; Bacteroides finegoldii DSM 17565; Bacteroides sp.1_1_30; MLDAILWFGFG173GAKWSGGYKG115ATGTTGGACGCAATCCTT leotiomyceta; AILIFPYGVWC TGGTTTGGTTTCGGTGCA Unclassified; GAKWSGGYKG ATCTTGATCTTCCCTTAC GGGGTCTGGTGTGGGGCT AAATGGAGCGGCGGATAC AAGGGAMLTLEGLIAVL174IGSNHKSQK116ATGTTGACTTTGGAAGGT Hungatella hathewayi 12489931 SILLTAFGLGS CTTATCGCCGTGTTGTCC AIGSNHKSQK ATCCTTCTGACGGCATTC GGTCTGGGTAGTGCTATC GGCAGTAACCATAAATCT CAGAAGMRRRKRIQMKV175(QA)LIP117ATGCGCCGCCGTAAACGC Veillonella sp. oral taxon 158 str. MMVLGIVALVG ATTCAGATGAAAGTAATG F0412; PNHLQALIP ATGGTGTTAGGCATCGTG Veillonella parvula ATCC 17745; GCACTTGTGGGACCCAAC Veillonella parvula DSM 2008; CATCTGCAAGCCTTAATC CCG Veillonella sp.3_1_44; Veillonella dispar ATCC 17748; Veillonella parvula ACS-068-V- Sch12; Veillonella parvula HSIVP1; Veillonella sp.6_1_27; Veillonella sp. DORA_B_18_19_23; Veillonella rogosae JCM 15642; Veillonella dispar DORA_11; MKKNVWDKILK MNV118ATGAAAAAGAATGTCTGG Bacteroides uniformis ATCC 8492; VVIAVASAILG GACAAAATCCTTAAAGTT Bacteroides uniformis; ALGANAMNV GTAATCGCTGTCGCATCG Bacteroides uniformis CL03T00C23; GCCATCTTGGGCGCATTA Bacteroides sp. AR29; GGTGCAAACGCCATGAAT GTT Bacteroides stercoris CC31F; Bacteroides sp. D20; Butyricimonas virosa DSM 23226; Bacteroides stercoris ATCC 43183; Bacteroides salyersiae WAL 10018 = DSM 18765 = JCM 12988; uncultured Bacteroides sp.; Bacteroides coprophilus DSM 18228 = JCM 13818; Bacteroides uniformis dnLKV2; MQQKWVKVTAV176(LA)ALIK119ATGCAACAGAAGTGGGTG Clostridium sp. CAG:277 ILAALMAVSRP AAGGTTACTGCGGTCATT GVGLAALIK TTGGCCGCACTGATGGCC GTATCTCGCCCCGGCGTT GGGTTGGCGGCGTTAATC AAA MKKTWSMILKV ATM120ATGAAGAAAACTTGGAGC Bacteroides sp.43_46; IIAVAGAIAGV ATGATTCTGAAGGTCATC Bacteroides caccae ATCC 43185; IGVQAATM ATTGCAGTTGCAGGAGCA Bacteroides ovatus CL02T12C04; ATCGCCGGAGTTATTGGT Bacteroides caccae CL03T12C61; GTGCAGGCAGCGACAATG Bacteroides eggerthii 1_2_48FAA; Bacteroides sp. CAG:98; Bacteroides congonensis; Bacteroides ovatus SD CMC 3f; Bacteroides sp. HMSC067B03; Bacteroides sp.1_1_14; Bacteroides caccae CAG:21;MKNTWTLILKV177LNVCI121ATGAAGAATACCTGGACA Bacteroides dorei CL03T12C01 IITVATAVAGA CTGATTCTGAAAGTAATT LGLNVCI ATCACCGTGGCGACCGCC GTTGCTGGTGCGCTTGGC TTGAATGTTTGTATCMTRYIKTLSYL122ATGACGCGCTATATTAAAClostridiales bacterium 42_27; FAAMAGVCFVS ACTCTGTCGTATCTGTTC Faecalibacterium prausnitzii M21 / 2; GLAVLSE GCCGCTATGGCCGGGGTG Clostridiales bacterium 52_15; TGCTTTGTAAGTGGACTG GCAGTGCTTAGTGAGMTVISVLCTMC178K123ATGACGGTGATTTCCGTG Odoribacter RGILKAIEYIGGAAALSKGILK CTGTGTACCATGTGTGGC AIEYIGR GCTGCCGCCTTATCCAAG GGCATCTTAAAAGCCATC GAATACATTGGGCGTMVTIMTLAVVA179IHLGNKINFKS124ATGGTCACTATTATGACA Prevotella timonensis CRIS 5C-B1; ITVAQAIHLGN K TTGGCCGTTGTAGCTATT Prevotella timonensis S9-PR14; KINFKSK ACAGTAGCGCAAGCCATT Prevotella timonensis 4401737 = CACCTTGGAAATAAGATC DSM 22865 = JCM 15640; AATTTCAAGAGTAAGMKALFSYILST180C125ATGAAAGCCTTATTTTCA Clostridiales; GLKVEGGIAVLSGMAGLCLVGGIA TATATTTTGTCTACTATG [Clostridium] leptum DSM 753; VLSGGKE GCGGGATTATGCCTTGTC GGAGGAATCGCGGTCCTG TCAGGAGGAAAGGAGMNMQSLFTLLP181TIKEI126ATGAACATGCAAAGTCTGFirmicutes bacterium CAG:24; FIVLAIGITRV TTCACGCTGTTACCGTTC Bilophila wadsworthia ATCC 49260; YCTIKEI ATTGTCCTTGCAATCGGT ACAATCAAGGAAATCMMILGMILALV182E127ATGATGATTTTGGGCATG Prevotella copri DSM 18205 AYGARFNMKNFVAAYAEYGARF ATCTTGGCTCTTGTAGTT NMKNFA GCGGCGTATGCCGAATAT GGTGCTCGCTTCAACATG AAAAACTTCGCGMITVMILLVVG183IHVNNKMEMGK128ATGATTACAGTGATGATC Prevotella sp. CAG:386 AMVAQAIHVNN TTGCTGGTCGTGGGCGCG KMEMGK ATGGTAGCTCAAGCCATC CATGTCAATAACAAAATG GAGATGGGAAAGMGPSFVMAALA184KATGK129ATGGGACCGTCGTTTGTCSubdoligranulum sp.60_17; GLLVVVGIVSK ATGGCGGCATTAGCTGGC Clostridiales bacterium 59_14; ATGK CTTTTGGTGGTCGTGGGT ATTGTATCTAAGGCCACC GGCAAG MVFMMTFAVVA185(A)VNVENKLD130ATGGTTTTTATGATGACG Bacteroides; VMIAQAVNVEN TTCGCCGTAGTTGCGGTG Prevotella sp. CAG:386; KLD ATGATTGCACAAGCTGTG AACGTAGAAAATAAATTG GAT MIALGIVIIAL186(CYLVYALA)N131ATGATTGCCCTTGGGATT uncultured Flavonifractor sp.; ACYLVYALANP PEKF GTCATTATCGCATTAGCT Clostridium orbiscindens EKF TGCTATCTGGTATATGCA 1_3_50AFAA; CTGGCTAATCCAGAGAAA Clostridia; TTT Lachnospiraceae bacterium 7_1_58FAA; Flavonifractor plautii ATCC 29863; Clostridiales bacterium UBA1707; Oscillospiraceae; unclassified Clostridiales; Clostridium sp. ATCC BAA-442; Alistipes finegoldii; Oscillibacter; Clostridiales; MILKVVIAVAS187(ANA)MNL132ATGATCCTTAAAGTAGTG Bacteroides ovatus SD CMC 3f; ALAGVLGANAM ATCGCAGTCGCTTCCGCA Bacteroides caccae ATCC 43185; NL TTAGCGGGTGTGTTGGGA Bacteroides ovatus CL03T12C18; GCTAATGCGATGAATCTT Bacteroides ovatus CL02T12C04; Bacteroides xylanisolvens CL03T12C04; Bacteroides sp.3_1_23; Bacteroides caccae CL03T12C61; Bacteroides ovatus; Bacteroides sp. D2; Bacteroides sp.43_46; The nucleic acid sequence may comprise a nucleotide sequence substantially as set out in any of SEQ ID No: 67-132, or a variant or fragment thereof. Provided below in Table 2 is a ranking number for each of SEQ ID No: 1-66. Without being bound by a singular interpretation, the inventors have ranked each of SEQ ID No: 1-66 based on the potency for use in therapy in human. It will be appreciated, therefore, that the lower the ranking number, the greater the potency of the peptide when used therapeutically, i.e., ranking number 1 is more potent than ranking number 66. Table 2: Ranking number for SEQ ID No: 1-66. SEQ ID Ranking SEQ ID Ranking SEQ ID Ranking SEQ ID Ranking No: No: No: No: No: No: No: No: 1 33 18 43 35 59 52 63 2 45 19 13 36 23 53 9 3 46 20 10 37 22 54 7 4 47 21 15 38 1 55 64 5 25 22 55 39 53 56 65 6 16 23 30 40 39 57 18 7 48 24 56 41 24 58 4 8 42 25 52 42 12 59 3 9 36 26 27 43 5 60 40 10 32 27 11 44 28 61 6 11 49 28 20 45 8 62 66 12 17 29 29 46 35 63 54 13 50 30 57 47 38 64 41 14 51 31 34 48 60 65 31 15 14 32 21 49 61 66 44 16 37 33 2 50 26 17 19 34 58 51 62 It will be appreciated that each of the amino acid sequences substantially as set out in SEQ ID No: 1-66 is a representative of a larger cluster of peptides found across bacterial species. Thus, by the term “variant or fragment thereof”, it will be appreciated that the invention extends to any amino acid, or variant, fragment, derivative, or analogue thereof, which comprises substantially the amino acid (or corresponding nucleic acid sequences) of any of the sequences referred to herein, including functional variants or functional fragments thereof, irrespective of the peptide cluster or bacterial species from which it is derived. The full length or mature amino acid sequences described herein as SEQ ID No: 1-66 may be functional. Such sequences may comprise a signal peptide at their N-terminus. However, the signal sequences may be cleaved from any of the peptides of the invention to result in shorter fragments of the longer peptides, and the fragments may also be functional. Hence, in one embodiment, the amino acid sequences substantially as set out in SEQ ID No: 1-66 may be cleaved into shorter, mature peptides that may be the active form. In one embodiment, the amino acid sequences substantially as set out in SEQ ID No: 1-66 may be cleaved to remove one, two, or three amino acid residues. In another embodiment, the amino acid sequences substantially as set out in SEQ ID No: 1-66 may be cleaved to remove four, five, or six amino acid residues. In further embodiments, the amino acid sequences substantially as set out in SEQ ID No: 1-66 may be cleaved to remove 10, 15, or 20 amino acid residues. Alternatively, the amino acid sequences substantially as set out in SEQ ID No: 1- 66 may be cleaved to remove 25, 30 or 35 amino acid residues. Preferably, the amino acids cleaved from the amino acid sequences substantially as set out in SEQ ID No: 1-66 are removed from the N-terminus. Preferably, the amino acids cleaved from the amino acid sequences substantially as set out in SEQ ID No: 1-66 are removed from the C-terminus. Preferably, the amino acid sequences substantially as set out in SEQ ID No: 1-66 are internally cleaved, i.e. in between the N- and C-terminus. As shown in Table 1, many of the peptides of SEQ ID No: 1-66 may be cleaved, and these have amino acid sequences of SEQ ID No: 133-187. In addition, the nucleic acid sequence may comprise a nucleotide sequence which encodes any one of the peptides of SEQ ID No: 133-187, or a variant or fragment thereof. It will be appreciated that some of the predicted mature peptide amino acid sequences are shorter than four amino acids in length, and, accordingly, have not been assigned a SEQ ID, as shown in Table 1. However, it will be appreciated that these shorter sequences remain a part of the claimed invention. Thus, preferably the peptide of the invention comprises an amino acid sequence substantially as set out as SEQ ID No: 133-187, or a variant or fragment thereof, or a nucleic acid encoding one or more of the peptide, or a variant or fragment thereof. Such fragments may be used in therapy, and preferably for use in treating, preventing, or ameliorating a disease caused by, or associated with, the gut-brain-axis. Furthermore, using bioinformatic approaches, the inventors have surprisingly identified seven of the screened peptides as having known, though not necessarily characterised, domains. These domains are as follows: (i) a thioredoxin superfamily-like CxxC domain (screened from the peptide comprising an amino acid sequence substantially as set out as SEQ ID No: 8). Human Thioredoxin 1 has been implicated in binding to human HSP90 at neural synapses, (Azarnia Tehran et al., 2017) and in the activity of botulinum neurotoxins at nerve synapses (Pirazzini et al, 2022). A different 16 amino acid CxxC motif-containing peptide derived from human Macrophage Migration Inhibitory Factor, a protein implicated in various human physiology and disease processes, such as neuroendocrine function (Lerch et al, 2014) and immunostimulatory behaviour (Nguyen et al., 2003), as a peptide, has redox activity and glucocorticoid overriding and proliferation-enhancing activity (Nguyen et al.2003). One peptide, SEQ ID No:8, is Clostridial thioredoxin; (ii) AgrD domain (screened from the peptides comprising amino acid sequences substantially as set out as SEQ ID No: 7 and SEQ ID No: 32), whereby the AgrD protein is a precursor to an autoinducing peptide, a quorum-sensing molecule); (iii) DUF3789 domain (screened from the peptides comprising amino acid sequences substantially as set out as SEQ ID No: 12 and SEQ ID No: 26), which is an uncharacterised bacterial protein domain; (iv) SCIFF domain (screened from the peptide comprising an amino acid sequence substantially as set out as SEQ ID No: 9), which is a domain associated with a small ribosomally synthesised natural product of unknown function; and (v) Target ACGX domain (screened from the peptide comprising an amino acid sequence substantially as set out as SEQ ID No: 11), which too is a domain of unknown function, proposed to be modified by adjacent SAM / SPASM enzymes. Thus, preferably, the peptide comprising an amino acid sequence substantially as set out as any one of SEQ ID No: 1-66, or a variant or fragment thereof, may comprise a CxxC-motif containing thioredoxin-superfamily-like domain. Preferably, the amino acid sequence substantially as set out in SEQ ID No: 8, or a variant or fragment thereof, comprises a CxxC-motif containing thioredoxin- superfamily-like domain. Thus, preferably the nucleic acid encoding SEQ ID No: 74, or a variant or fragment thereof, encodes a CxxC-motif containing thioredoxin-superfamily-like domain. Preferably, the peptide comprising an amino acid sequence substantially as set out as any one of SEQ ID No: 1-66, or a variant or fragment thereof, may comprise an AgrD domain. Preferably, the amino acid sequences substantially as set out in SEQ ID No: 7 and / or SEQ ID No: 32, or a variant or fragment thereof, comprise an AgrD domain. Thus, preferably the nucleic acid encoding SEQ ID No: 73 and / or SEQ ID No: 98, or a variant or fragment thereof, encodes an AgrD domain. Preferably, the peptide comprising an amino acid sequence substantially as set out as any one of SEQ ID No: 1-66, or a variant or fragment thereof, may comprise a DUF3789 domain. Preferably, the amino acid sequences substantially as set out in SEQ ID No: 12 and / or SEQ ID No: 26, or a variant or fragment thereof, comprise a DUF3789 domain. Thus, preferably the nucleic acid encoding SEQ ID No: 78 and / or SEQ ID No: 92, or a variant or fragment thereof, encodes a DUF3789 domain. Preferably, the peptide comprising an amino acid sequence substantially as set out as any one of SEQ ID No: 1-66, or a variant or fragment thereof, may comprise an SCIFF domain. Preferably, the amino acid sequence substantially as set out in SEQ ID No: 9, or a variant or fragment thereof, comprises an SCIFF domain. Thus, preferably the nucleic acid encoding SEQ ID No: 75, or a variant or fragment thereof, encodes an SCIFF domain. Preferably, the peptide comprising an amino acid sequence substantially as set out as any one of SEQ ID No: 1-66, or a variant or fragment thereof, may comprise a Target ACGX domain. Preferably, the amino acid sequence substantially as set out in SEQ ID No: 11, or a variant or fragment thereof, comprises a Target ACGX domain. Thus, preferably the nucleic acid encoding SEQ ID No: 77, or a variant or fragment thereof, encodes a Target ACGX domain. The nucleic acid molecule may be an isolated or purified nucleic acid sequence. The nucleic acid sequence may be a DNA sequence. The nucleic acid molecule may comprise synthetic DNA. The nucleic acid molecule may comprise cDNA. The nucleic acid may be operably linked to a heterologous promoter. The nucleic acid sequence encoding the peptide, derivative, or analogue thereof, may be incorporated into a genetic construct for use in gene therapy or for cloning purposes. In one embodiment, the nucleic acid may encode one peptide selected from SEQ ID No: 1-66, or variant or fragment thereof. For example, the fragment may be any of the sequences selected from SEQ ID No: 133-187, or a variant or fragment thereof. In another embodiment, however, the nucleic acid may encode a plurality of peptides selected from SEQ ID No: 1-66, or variant or fragment thereof. For example, the plurality of fragments may be any of the sequences selected from SEQ ID No: 133-187, or a variant or fragment thereof. For example, the nucleic acid may encode the peptide of SEQ ID No: 1, or variant or fragment thereof, and the nucleic acid may encode the peptide of SEQ ID No: 2, or variant or fragment thereof, and so on. Any combination of the peptides may be encoded by the nucleic acid. In one preferred embodiment, therefore, the nucleic acid molecule encoding the peptide, or variant or fragment thereof is a genetic construct. More preferably, the nucleic acid molecule or genetic construct is provided in a recombinant vector. Genetic constructs of the invention may be in the form of an expression cassette, which may be suitable for expression of the encoded peptide, variant or fragment thereof, in a host cell. The genetic construct may be introduced into a host cell without it being incorporated in a vector. For instance, the genetic construct, which may be a nucleic acid molecule, may be incorporated within a liposome or a virus particle. Alternatively, a purified nucleic acid molecule (e.g. histone-free DNA, or naked DNA) may be inserted directly into a host cell by suitable means, e.g. direct endocytotic uptake. For cloning purposes, the genetic construct may be introduced directly into cells of a host subject (e.g. a bacterial, eukaryotic or animal cell) by transfection, infection, electroporation, microinjection, cell fusion, protoplast fusion or ballistic bombardment. Alternatively, genetic constructs of the invention may be introduced directly into a host cell using a particle gun. Alternatively, the genetic construct may be harboured within a recombinant vector, for expression in a suitable host cell. For administration to the subject being treated, the construct may be contained in a phage delivery system, such as AAV. The recombinant vector may be a plasmid, cosmid or phage. Such recombinant vectors are useful for transforming host cells with the genetic construct, and for replicating the expression cassette therein. The skilled technician will appreciate that genetic constructs of the invention may be combined with many types of backbone vector for expression purposes. Recombinant vectors may include a variety of other functional elements including a suitable promoter to initiate gene expression. For instance, the recombinant vector may be designed such that it autonomously replicates in the cytosol of the host cell. In this case, elements, which induce or regulate DNA replication, may be required in the recombinant vector. Alternatively, the recombinant vector may be designed such that it integrates into the genome of a host cell. To facilitate cloning, the recombinant vector may also comprise DNA coding for a gene that may be used as a selectable marker in the cloning process, i.e. to enable selection of cells that have been transfected or transformed, and to enable the selection of cells harbouring vectors incorporating heterologous DNA. Alternatively, the selectable marker gene may be in a different vector to be used simultaneously with vector containing the gene of interest. The vector may also comprise DNA involved with regulating expression of the coding sequence, or for targeting the expressed polypeptide to a certain part of the host cell. It will be appreciated that the peptide, variant or fragment thereof, or the nucleic acid encoding the one or more peptide, variant or fragment thereof according to the invention may be used in a medicament, which may be used as a monotherapy (i.e. use of the peptide, variant or fragment thereof, or the nucleic acid, alone), for treating, preventing, or ameliorating conditions that are caused by, or are associated with, the gut-brain-axis. Alternatively, the peptide, variant or fragment thereof or nucleic acid according to the invention may be used as an adjunct to, or in combination with, known therapies for treating, preventing, or ameliorating conditions that are caused by, or are associated with, the gut-brain-axis. The peptide or nucleic acid according to the invention may be combined in compositions having a number of different forms depending, in particular, on the manner in which the composition is to be used. Thus, for example, the composition may be in the form of a powder, tablet, capsule, liquid, ointment, cream, gel, hydrogel, aerosol, spray, micellar solution, transdermal patch, liposome suspension or any other suitable form that may be administered to a person or animal in need of treatment. It will be appreciated that the vehicle of medicaments according to the invention should be one which is well-tolerated by the subject to whom it is given. Medicaments comprising the peptide according to the invention may be used in a number of ways. For instance, oral administration may be required, in which case the peptide may be contained within a composition that may, for example, be ingested orally in the form of a tablet, capsule or liquid. The peptide or nucleic acid of the invention may be formulated with a mucosal adhesive, preferably for adhering to the buccal mucosa. The peptide of the invention may be formulated with a cell membrane permeability enhancer, penetration enhancer and / or absorption enhancer. The peptide or nucleic acid according to the invention may also be incorporated within a slow- or delayed-release device. Such devices may, for example, be inserted on or under the skin, and the medicament may be released over weeks or even months. The device may be located adjacent to the treatment site. Such devices may be particularly advantageous when long-term treatment with peptides used according to the invention is required and which would normally require frequent administration (e.g. daily injection). In a preferred embodiment, medicaments according to the invention may be administered to a subject by injection into the blood stream or directly into a site requiring treatment. For example, the medicament may be injected close to, or at least adjacent to the pancreatic islets. Injections may be intravenous (bolus or infusion), intramuscular (bolus or infusion), subcutaneous (bolus or infusion), or intradermal (bolus or infusion). It will be appreciated that the amount of the peptide or nucleic acid that is required is determined by its biological activity and bioavailability, which in turn depends on the mode of administration, the physiochemical properties of the peptide or nucleic acid and whether it is being used as a monotherapy or in a combined therapy. The frequency of administration will also be influenced by the half-life of the peptide within or on the subject being treated. Optimal dosages to be administered may be determined by those skilled in the art, and will vary with the particular peptide in use, the strength of the pharmaceutical composition, and the mode of administration. Additional factors depending on the particular subject being treated will result in a need to adjust dosages, including subject age, weight, gender, diet, and time of administration. Optimal dosages may be determined depending on the severity of the condition that is caused by, or is associated with, the gut-brain-axis. The peptide or nucleic acid may be administered before, during or after onset of symptoms associated with a condition that is caused by, or is associated with, the gut-brain-axis. Daily doses may be given as a single administration (e.g. a single daily application). Alternatively, the peptide may require administration twice or more times during a day. Alternatively, a slow-release device may be used to provide optimal doses of the peptide according to the invention to a patient without the need to administer repeated doses. Known procedures, such as those conventionally employed by the pharmaceutical industry (e.g. in vivo experimentation, clinical trials, etc.), may be used to form specific formulations of the peptide according to the invention and precise therapeutic regimes (such as daily doses of the agents and the frequency of administration). Hence, in a fourth aspect of the invention, there is provided a pharmaceutical composition for treating, preventing or ameliorating a disease, that is caused by, or associated with, the gut-brain-axis, comprising a therapeutically effective amount of a peptide comprising an amino acid sequence substantially as set out in SEQ ID No: 38, 33, 59, 58, 43, 1-32, 34-37, 39-42, 44-57, 60-66, or a variant or fragment thereof, or a nucleic acid encoding one or more of the peptide, or variant or fragment thereof, and a pharmaceutically acceptable vehicle. The invention also provides, in a fifth aspect, a process for making the pharmaceutical composition according to claim 18, the process comprising combining a therapeutically effective amount of a peptide comprising an amino acid sequence substantially as set out in SEQ ID No: 38, 33, 59, 58, 43, 1-32, 34-37, 39-42, 44-57, 60-66, or a variant or fragment thereof, or a nucleic acid encoding one or more of the peptide, or variant or fragment thereof with a pharmaceutically acceptable vehicle. The peptide variant or fragment may be any of the sequences selected from SEQ ID No: 133-187, or a variant or fragment thereof. A “subject” may be a vertebrate, mammal, or domestic animal. Hence, medicaments according to the invention may be used to treat any mammal, for example livestock (e.g. a horse), pets, or may be used in other veterinary applications. Most preferably, however, the subject is a human being. A “therapeutically effective amount” of peptide is any amount which, when administered to a subject, is the amount of active agent that is needed to treat, ameliorate, or prevent a disease that is caused by, or associated with, the gut- brain-axis, or produce the desired effect. The peptide, variant or fragment thereof may be used as an adjuvant for the prevention or treatment of a disease caused by, or associated with, the gut-brain-axis. This means that lower doses of other prophylactic or therapeutic treatments may be required. A “pharmaceutically acceptable vehicle” as referred to herein, is any known compound or combination of known compounds that are known to those skilled in the art to be useful in formulating pharmaceutical compositions. In one embodiment, the pharmaceutically acceptable vehicle may be a solid, and the composition may be in the form of a powder or tablet. A solid pharmaceutically acceptable vehicle may include one or more substances which may also act as flavouring agents, lubricants, solubilisers, suspending agents, dyes, fillers, glidants, compression aids, inert binders, sweeteners, preservatives, coatings, or tablet-disintegrating agents. The vehicle may also be an encapsulating material. In powders, the vehicle is a finely divided solid that is in admixture with the finely divided active agents according to the invention. In tablets, the active agent (i.e. the peptide or nucleic acid) may be mixed with a vehicle having the necessary compression properties in suitable proportions and compacted in the shape and size desired. Suitable solid vehicles include, for example, calcium phosphate, magnesium stearate, talc, sugars, lactose, dextrin, starch, gelatin, cellulose, polyvinylpyrrolidine, low melting waxes and ion exchange resins. In another embodiment, the pharmaceutical vehicle may be a gel and the composition may be in the form of a cream or the like. However, the pharmaceutical vehicle may be a liquid, and the pharmaceutical composition is in the form of a solution. Liquid vehicles are used in preparing solutions, suspensions, emulsions, syrups, elixirs and pressurised compositions. The active agent according to the invention (i.e. the peptide or nucleic acid) may be dissolved or suspended in a pharmaceutically acceptable liquid vehicle such as water, an organic solvent, a mixture of both or pharmaceutically acceptable oils or fats. The liquid vehicle can contain other suitable pharmaceutical additives such as solubilisers, emulsifiers, buffers, preservatives, sweeteners, flavouring agents, suspending agents, thickening agents, colours, viscosity regulators, stabilisers or osmo-regulators. Suitable examples of liquid vehicles for oral and parenteral administration include water (partially containing additives as above, e.g. cellulose derivatives, preferably sodium carboxymethyl cellulose solution), alcohols (including monohydric alcohols and polyhydric alcohols, e.g. glycols) and their derivatives, and oils (e.g. fractionated coconut oil and arachis oil). For parenteral administration, the vehicle can also be an oily ester such as ethyl oleate and isopropyl myristate. Sterile liquid vehicles are useful in sterile liquid form compositions for parenteral administration. The liquid vehicle for pressurised compositions can be a halogenated hydrocarbon or other pharmaceutically acceptable propellant. Liquid pharmaceutical compositions, which are sterile solutions or suspensions, can be utilised by, for example, intramuscular, intrathecal, epidural, intraperitoneal, intravenous and particularly subcutaneous injection. The peptide may be prepared as a sterile solid composition that may be dissolved or suspended at the time of administration using sterile water, saline, or other appropriate sterile injectable medium. The peptide and compositions of the invention may be administered orally in the form of a sterile solution or suspension containing other solutes or suspending agents (for example, enough saline or glucose to make the solution isotonic), bile salts, acacia, gelatin, sorbitan monoleate, polysorbate 80 (oleate esters of sorbitol and its anhydrides copolymerised with ethylene oxide) and the like. The peptide used according to the invention can also be administered orally either in liquid or solid composition form. Compositions suitable for oral administration include solid forms, such as pills, capsules, granules, tablets, and powders, and liquid forms, such as solutions, syrups, elixirs, and suspensions. Preferably, orally administrable formulations do not dissolve in the stomach, but preferentially dissolve in the duodenum. Orally administrable formulations may be enterically-coated, for example enteric-coated tablets or capsules. Forms useful for parenteral administration include sterile solutions, emulsions, and suspensions. It will be appreciated that the invention extends to any nucleic acid or peptide or variant, derivative, or analogue thereof, which comprises substantially the amino acid or nucleic acid sequences of any of the sequences referred to herein, including functional variants or functional fragments thereof. The terms “substantially the amino acid / nucleotide / peptide sequence”, “functional variant” and “functional fragment”, can be a sequence that has at least 40% sequence identity with the amino acid / nucleotide / peptide sequences of any one of the sequences referred to herein, for example 40% identity with any of the sequences identified herein. Amino acid / polynucleotide / polypeptide sequences with a sequence identity which is greater than 65%, more preferably greater than 70%, even more preferably greater than 75%, and still more preferably greater than 80% sequence identity to any of the sequences referred to are also envisaged. Preferably, the amino acid / polynucleotide / polypeptide sequence has at least 85% identity with any of the sequences referred to, more preferably at least 90% identity, even more preferably at least 92% identity, even more preferably at least 95% identity, even more preferably at least 97% identity, even more preferably at least 98% identity and, most preferably at least 99% identity with any of the sequences referred to herein. The skilled technician will appreciate how to calculate the percentage identity between two amino acid / polynucleotide / polypeptide sequences. In order to calculate the percentage identity between two amino acid / polynucleotide / polypeptide sequences, an alignment of the two sequences must first be prepared, followed by calculation of the sequence identity value. The percentage identity for two sequences may take different values depending on:- (i) the method used to align the sequences, for example, ClustalW, BLAST, FASTA, Smith-Waterman (implemented in different programs), or structural alignment from 3D comparison; and (ii) the parameters used by the alignment method, for example, local vs global alignment, the pair-score matrix used (e.g. BLOSUM62, PAM250, Gonnet etc.), and gap-penalty, e.g. functional form and constants. Having made the alignment, there are many different ways of calculating percentage identity between the two sequences. For example, one may divide the number of identities by: (i) the length of shortest sequence; (ii) the length of alignment; (iii) the mean length of sequence; (iv) the number of non-gap positions; or (iv) the number of equivalenced positions excluding overhangs. Furthermore, it will be appreciated that percentage identity is also strongly length dependent. Therefore, the shorter a pair of sequences is, the higher the sequence identity one may expect to occur by chance. Hence, it will be appreciated that the accurate alignment of protein or DNA sequences is a complex process. The popular multiple alignment program ClustalW (Thompson et al., 1994, Nucleic Acids Research, 22, 4673-4680; Thompson et al., 1997, Nucleic Acids Research, 24, 4876-4882) is a preferred way for generating multiple alignments of proteins or DNA in accordance with the invention. Suitable parameters for ClustalW may be as follows: For DNA alignments: Gap Open Penalty = 15.0, Gap Extension Penalty = 6.66, and Matrix = Identity. For protein alignments: Gap Open Penalty = 10.0, Gap Extension Penalty = 0.2, and Matrix = Gonnet. For DNA and Protein alignments: ENDGAP = -1, and GAPDIST = 4. Those skilled in the art will be aware that it may be necessary to vary these and other parameters for optimal sequence alignment. Preferably, calculation of percentage identities between two amino acid / polynucleotide / polypeptide sequences may then be calculated from such an alignment as (N / T)*100, where N is the number of positions at which the sequences share an identical residue, and T is the total number of positions compared including gaps and either including or excluding overhangs. Preferably, overhangs are included in the calculation. Hence, a most preferred method for calculating percentage identity between two sequences comprises (i) preparing a sequence alignment using the ClustalW program using a suitable set of parameters, for example, as set out above; and (ii) inserting the values of N and T into the following formula:- Sequence Identity = (N / T)*100. Alternative methods for identifying similar sequences will be known to those skilled in the art. For example, a substantially similar nucleotide sequence will be encoded by a sequence, which hybridises to DNA sequences or their complements under stringent conditions. By stringent conditions, we mean the nucleotide hybridises to filter-bound DNA or RNA in 3x sodium chloride / sodium citrate (SSC) at approximately 45ºC followed by at least one wash in 0.2x SSC / 0.1% SDS at approximately 20-65ºC. Alternatively, a substantially similar peptide may differ by at least 1, 2, 3, 4 or 5 amino acids from any of the sequences identified herein. Due to the degeneracy of the genetic code, it is clear that any nucleic acid sequence described herein could be varied or changed without substantially affecting the sequence of the protein encoded thereby, to provide a functional variant thereof. Suitable nucleotide variants are those having a sequence altered by the substitution of different codons that encode the same amino acid within the sequence, thus producing a silent change. Other suitable variants are those having homologous nucleotide sequences but comprising all, or portions of, sequence, which are altered by the substitution of different codons that encode an amino acid with a side chain of similar biophysical properties to the amino acid it substitutes, to produce a conservative change. For example, small non- polar, hydrophobic amino acids include glycine, alanine, leucine, isoleucine, valine, proline, and methionine. Large non-polar, hydrophobic amino acids include phenylalanine, tryptophan and tyrosine. The polar neutral amino acids include serine, threonine, cysteine, asparagine and glutamine. The positively charged (basic) amino acids include lysine, arginine and histidine. The negatively charged (acidic) amino acids include aspartic acid and glutamic acid. It will therefore be appreciated which amino acids may be replaced with an amino acid having similar biophysical properties, and the skilled technician will know the nucleotide sequences encoding these amino acids. In another aspect, there is provided a peptide comprising an amino acid sequence substantially as set out as SEQ ID No: 1-66, or a variant or fragment thereof, or a nucleic acid encoding one or more of the peptide, or a variant or fragment thereof, for use in therapy. In another aspect, there is provided a peptide comprising an amino acid sequence substantially as set out as SEQ ID No: 1-66, or a variant or fragment thereof, or a nucleic acid encoding one or more of the peptide, or a variant or fragment thereof, for use in treating, preventing, or ameliorating a disease caused by, or associated with, the gut-brain-axis. In another aspect, there is provided a method of treating, preventing, or ameliorating a disease caused by, or associated with, the gut-brain-axis, the method comprising, administering or having administered, to a subject in need of such treatment, a therapeutically effective amount of a peptide comprising an amino acid sequence substantially as set out as SEQ ID No: 1-66, or a variant or fragment thereof, or a nucleic acid encoding one or more of the peptide, or a variant or fragment thereof. In another aspect, there is provided a pharmaceutical composition for treating, preventing or ameliorating a disease, that is caused by, or associated with, the gut-brain-axis, comprising a therapeutically effective amount of a peptide comprising an amino acid sequence substantially as set out in SEQ ID No: 1-66, or a variant or fragment thereof, or a nucleic acid encoding one or more of the peptide, or variant or fragment thereof, and a pharmaceutically acceptable vehicle. In another aspect, there is provided a process for making the pharmaceutical composition according to the fourth aspect, the process comprising combining a therapeutically effective amount of a peptide comprising an amino acid sequence substantially as set out in SEQ ID No: 1-66, or a variant or fragment thereof, or a nucleic acid encoding one or more of the peptide, or variant or fragment thereof with a pharmaceutically acceptable vehicle. All of the features described herein (including any accompanying claims, abstract and drawings), and / or all of the steps of any method or process so disclosed, may be combined with any of the above aspects in any combination, except combinations where at least some of such features and / or steps are mutually exclusive. For a better understanding of the invention, and to show how embodiments of the same may be carried into effect, reference will now be made, by way of example, to the accompanying Figures, in which:- Figure 1 illustrates a bioinformatics pipeline to select peptides for screening. A) Sberro et al. identified 4,539 putative small protein clusters from healthy human metagenomic datasets. B) From these clusters, the inventors identified 2,412 unique sequences (‘Complete library’) that were (1) found in gut samples, and (2) predicted to be transmembrane or secreted. C) To create the ‘Pilot library’, the inventors selected one representative sequence from each of the 236 clusters found in the Complete library. Figure 2 illustrates the impact of 66 peptides on worm behaviour across two independent screens. Impact was quantified in terms of the number of features significantly changed relative to a control strain. See “Materials and Methods” section for details of the specific screens that were used. Toxin = Cry6A protein from Bacteroides thuringiensis. Figure 3 illustrates the impact of 13 peptides, obtained from the subset of 66 peptides, on worm behaviour across four screens. Impact was quantified in terms of the number of features significantly changed relative to a control strain. See “Materials and Methods” section for details of specific screens. Screen 4 included the addition of rhamnose to tune peptide expression. Toxin = Cry6A protein from Bacteroides thuringiensis. Figure 4 depicts the principal component analysis (PCA) of worm responses to 66 peptides and selected therapeutic drugs. Peptides SEQ ID No: 1 and SEQ ID No 48 are indicated for clarity. Figure 5 depicts the principal component analysis (PCA) of worm responses to 66 peptides and a full panel of therapeutic drugs. The peptide dataset is labelled in black, and the therapeutic drug dataset is labelled in colour. Figure 6 depicts the feature scores for representative behavioural changes in screen 1. Each dot represents the averaged feature score across all worms in one replicate well of each condition. Different coloured dots refer to the three different imaging days. The features shown are: d_area_w_paused_90th_poststim, speed_head_base_w_backward_50th_bluelight, relative_to_body_angular_velocity_neck_w_backward_abs_50th_bluelight. Feature explanations can be found through the following URL: https: / / github.com / ver228 / tierpsy- tracker / blob / master / docs / OUTPUTS.md#basename_featuresnhdf5-tierpsy- features. Figure 7 depicts a heatmap of hierarchically clustered behavioural changes induced by human drugs and peptides of SEQ ID No: 1-66. Each box represents averaged feature score across all worms from Screen 1 and 2 for peptides or for a given drug. Columns represent features from the Tierpsy256 feature set and rows represent unique drug or peptide conditions. Examples The inventors began their investigation with 467,538 small proteins, obtained from metagenomic datasets, from which a select subset were expressed in E. coli. Subsequent behavioural screening assays in C. elegans worms surprisingly revealed significant observed changes in behavioural features of worms fed on E. coli engineered to heterologously express one of 66 peptides naturally encoded by, and predicted to be secreted by, bacterial members of the healthy human microbiota. Thus, the inventors unexpectedly discovered 66 peptides with evidence of potential neuromodulatory activity based on quantifiable modulation of C. elegans behavioural features, activity which could be harnessed in a therapeutic context for a wide range of diseases caused by, or associated with, the microbiome gut-brain-axis. Materials and Methods Identification and expression of small proteins The inventors utilised a published study (Sberro et al., 2019. Cell) for the identification of peptides and peptide families from metagenomic datasets (Steps in part A of diagram below). A set of bacterial small protein / peptide sequences, both found within human gut metagenomic sequences and predicted to be transmembrane or secreted, were identified through the utilisation of SignalP 5.0 and Phobius software. The detailed bioinformatics pipeline used to select peptides for screening is illustrated in Figure 1. The resultant 236 sequences were codon optimised for expression in E. coli, and subsequently synthesised and cloned for expression in E. coli Lemo21 cells. A subset of the 236 sequences was then tested in behavioural screening assays in C. elegans worms. Behavioural screen of small protein expression library The peptides’ effects on worm behaviour were determined by a standard phenotyping assay, similar that described in Brown et al., 2022. E. coli were grown as lawns on 96-well NGM / LB agar plates, and expression of peptides was induced overnight with 0.5 mM IPTG. The C. elegans N2 nematode worm strain was then dispensed onto pre-grown bacterial lawns, and, after approximately four hours of exposure, worms were recorded for 15 minutes using high- resolution megapixel cameras, and behavioural features were quantified using Tierpsy worm tracking software. Where relevant, refer to detailed methods and references from Barlow et al (2022). Worm strains The C. elegans N2 strain was used in this work; worms were cultured on Nematode Growth Medium (NGM) agar at 20ௗ°C and fed with E. coli Lemo21 following standard procedures. Standard phenotyping assay A standard phenotyping assay protocol was followed, as detailed in the following protocol: doi.org / 10.17504 / protocols.io.bsicncaw. There were two notable differences from standard protocol, in that where OP50 is mentioned, the inventors used E. coli Lemo21, and where low peptone NGM plates are described, the inventors used LB NGM plates. Briefly, Day 1 adult worms were obtained by bleach-synchronisation, as detailed in the following protocol: doi.org / 10.17504 / protocols.io.2bzgap6, and were subsequently used for all imaging experiments. Imaging plates were prepared by filling 96 well plates with 200ௗμL of LB NGM agar + 0.5 mM IPTG (to induce peptide expression) per well using an Integra VIAFILL reagent dispenser (INTEGRA Biosciences Ltd, UK), as detailed in the following protocol: doi.org / 10.17504 / protocols.io.bmxbk7in, and were stored at 4ௗ°C until use. Screens 1-2: Screen 1 involved a phenotypic assay of a subset of the 236 sequences described above. Screen 2 involved repeat phenotypic assays for E. coli strains with significant features from the Screen 1.104 strains (revealed to express 66 unique peptides following DNA sequencing) were associated with significant behavioural changes in worms across both assays. Three days before imaging, the inventors inoculated the E. coli expression library from frozen glycerol stock plates in 96 well microplates filled with LB and 50 µg / mL kanamycin. These plates were incubated at 37°C overnight. Two days before imaging, the inventors inoculated the overnight culture into new 96 well microplates filled with LB. These plates were incubated at 37°C overnight. Screen 3: Screen 3 involved a phenotypic assay of 13 peptides (from the subset of 66 peptides) that were associated with significant behavioural changes in worms in screens 1 and 2. Two days before imaging, the inventors inoculated the E. coli expression library from frozen glycerol stock plates in 96 well microplates filled with LB, 50 µg / mL kanamycin and 25 µg / mL chloramphenicol. These plates were then incubated at 37°C overnight. On the day before imaging, imaging plates were placed in a LEEC BC2 drying cabinet (LEEC Ltd, Nottingham, UK) to lose 3–5% weight (wherein the starting weight was 59ௗg without the lid, with a target weight of 56ௗg, and the process taking between two and threeௗhours in total). In screen 3, rhamnose was added to some wells, at a final concentration of 1 mM, for tuning peptide expression. Each imaging plate was then seeded with 10ௗμL per well of E. coli from the second overnight culture using a VIAFLO liquid handling pipettor (INTEGRA Biosciences Ltd, UK), and stored at room temperature overnight. The following day, synchronised Day 1 adults were washed in M9, as detailed in the following protocol: doi.org / 10.17504 / protocols.io.bfqbjmsn, and dispensed into imaging plate wells using either the COPAS 500 Flow Pilot worm sorter, as detailed in the following protocol: doi.org / 10.17504 / protocols.io.bfc9jiz6, in screens 1 and 2, or, using the VIAFILL reagent dispenser (INTEGRA Biosciences Ltd, UK) in screen 3. The inventors aimed to dispense three worms into each well. Imaging plates were then placed in a sterile culture hood for one hour to dry following liquid handling, before being returned to a 20ௗ°C incubator for two and a half hours and placed onto the multi-camera tracker for half an hour to acclimatise prior to image acquisition, with a total of four hours of exposure to peptide. Bright field illumination To prevent a light-avoidance response while illuminating the sample in bright field, the inventors used a dedicated 850ௗnm light system (Loopbio GmbH, Vienna, Austria), consisting of a 200 × 200ௗmm edge-lit LED panel. Briefly, the edge-lit configuration had the LEDs attached to the frame of the panel and shone into a horizontal light guide plate, which homogenised and diffused the light. This setup was characterised to provide a minimum radiance of 15ௗWௗm−2ௗsr−1, a minimum uniformity of 95ௗ±ௗ10%, and a half-angle (the angle at which the measured intensity falls to 50% its maximum value) of 30°. At 200 x 200 mm, the panel was significantly larger than the sample area, thus achieving the double goal of minimising edge effects, and thermally insulating the sample from the LED panel, as this can be placed at a relatively large distance of 65ௗmm. To further improve light collimation, two computer monitor privacy filters (3ௗM, Saint Paul, MN, USA) placed at right angles were inserted between the LED panel and the sample area. Image acquisition All videos were acquired at 25 fps on the trackers in a temperature-controlled room at 20ௗ°C, with a shutter time of 25ௗms, and 12.4ௗµm px−1resolution. For all experiments, three sequential videos were taken, run in series by a script: a five-minute pre-stimulus video, a six-minute blue light recording with ten-second blue light pulses set to 100% intensity at the 60, 160, and 260ௗsecond marks, and a five-minute post-stimulus recording. The timing of recordings and photostimulation was controlled using Loopbio’s API for Motif software in a script. Image processing and quality control Segmentation, tracking, and pose estimation over time was performed using Tierpsy Tracker. Each video was checked using Tierpsy Tracker’s Viewer, and wells with visible contamination, agar damage, or excess liquid (from worm sorter, such that worms swim rather than crawl) were marked as bad, and consequently were excluded from the analysis. Convolutional neural network to exclude non-worm objects Tierpsy Tracker uses a CNN classifier after segmentation to exclude non-worm objects from being analysed and skewing the results. In the video compression step at the beginning of the Tierpsy analysis pipeline, a segmentation algorithm detects putative worm objects according to a set of user-defined parameters. The pixels in the frame that are further away than a threshold from any of the putative worms are set to 0, creating a “Masked Video”. The objects selected by the masking algorithm are tracked throughout the video, but only now if they pass the filtering step powered by a CNN classifier. See publication for further details on CNN classifier. Video processing with multiple wells The utilisation of multiwell plates for imaging significantly increased the experimental throughput, though also introduced challenges for data analysis as each video output contains 16 separate wells. See publication for further details on past work to improve the processing of multiwell videos. Automatic extraction of behavioural features was performed on a per-worm basis, before worms were sorted into their respective wells based on their (x, y) coordinates in order to obtain well-averaged behavioural features. Data provenance The tracking of multiwell plates complicates the handling of metadata, since there is not a unique mapping between videos and experimental conditions. The inventors recorded experimental metadata for imaging with the camera arrays, and used an open-source module in Python to combine the experimental records, such to create a full metadata table with the experimental conditions for each well. Experimental records are typically compiled in the form of csv files. In each tracking day, the experimenter must record: i) information about the media type and the bacterial food present on the imaging plates, as well as the worm strains that were dispensed into the wells of the plates (as recorded in a summarised manner in the wormsorter.csv file), ii) information about the experimental runs, including the unique IDs of the imaging plates, the instrument name where each plate was imaged, as well as the environmental conditions (manual_metadata.csv), and iii) if applicable, information about the contents of the compound source plates (sourceplate.csv), and the mapping between imaging plates and source plates (imaging2source.csv). Using the functions in the hydra module, a plate metadata table was created to contain all the well-specific experimental conditions for every well of each unique imaging plate, including the compound contents if applicable. Then, the information about the experimental runs was merged with the plate metadata to create a final metadata table with the complete experimental conditions for every recording of every well. At this stage, the video filenames were also matched to the sample based on the camera array instrument ID. Statistics and reproducibility Each well contained multiple worms, though worm identity was not necessarily maintained across the duration of tracking. The inventors therefore used the number of wells as the sample size for statistical analysis, rather than the number of worms. All experiments were repeated across three independent tracking days. Analysis of time-resolved response to photostimulation Tierpsy Tracker17 was used to calculate a set of 3076 summary features for each well for each non-overlapping ten-second interval of the six-minute stimulus recording, with three ten-second blue light pulses starting at 60, 160, and 260 seconds. Samples where more than 40% of the features failed to be calculated were excluded from the analysis, as was any feature that failed to be calculated for more than 20% of the samples in any of the ten-second intervals. Missing values were then imputed by averaging the valid values within each time interval, and the feature matrix (all wells, in all time intervals) was then scaled by applying z-normalisation. Data analysis Scripts adapted from the tierpsytools Python library (https: / / github.com / Tierpsy / tierpsy-tools-python) were used to analyse the resulting feature matrix. Example 1 – Identification of peptides The inventors began their investigation with 4,539 small protein clusters, totalling 467,538 small proteins / small open reading frames (sORFs), as identified by Sberro et al., from which the inventors identified 2,412 unique sORFs that were found in gut samples and predicted to be transmembrane or secreted. From this subset, the inventors selected one representative sequence from each of the 236 clusters, such that there remained just 236 sORFs, as depicted in Figure 1. These 236 sequences were codon optimised for expression in E. coli, synthesised and cloned for expression in E. coli Lemo21 cells. A subset of the 236 sequences was then tested in behavioural screening assays in C. elegans worms, as further discussed in the following Examples. Example 2 - Impact of 66 peptides on worm behaviour The inventors tested a subset of the sequences from Example 1 in behavioural screening assays in C. elegans worms. In two independent screens, the inventors surprisingly observed significant changes in behavioural features of worms fed on E. coli Lemo21 bacteria engineered to heterologously express one of 66 peptides naturally encoded by, and predicted to be secreted by, bacterial members of the healthy human microbiota, as illustrated in Figure 2. Furthermore, expression of a known nematocidal toxin from Bacteroides thuringiensis, Cry6A, in the same bacterial strain, was used as a positive control for the assay, which also demonstrated extensive behavioural changes, as also illustrated in Figure 2. Example 3 – Impact of 13 peptides on worm behaviour The inventors also observed behavioural changes in follow-up screens of a subset of the 66 peptides, including in samples with added rhamnose for peptide expression tuning, as illustrated in Figure 3. Example 4 - Worm response to two peptides cluster with neuroactive drug responses Human neuroactive drugs have characteristic impacts on worm behaviour; the inventors compared the behavioural responses of the peptides across screens 1 and 2 to the results from a separate screen recording worm responses to a library of common therapeutic drugs (see Figures 4-5 and Figure 7). The effects of peptide with SEQ ID No: 1 and 67 and peptide with SEQ ID No: 48 and 114 cluster with responses to three of the screened drugs (see Figure 4 and Figure 7): Mebeverine hydrochloride, an antispasmodic that may affect calcium channels, Flunarizine dihydrochloride, a calcium antagonist that may also block serotonin and dopamine D2 receptors, and Clomiphene citrate, a drug used to induce ovulation, whose mode of action is unclear. Other peptides cluster separately from the drugs tested, as illustrated in Figures 4-5). These two peptides may, therefore, induce a phenotype that shares similarities with responses to the aforementioned drug cluster. Furthermore, the mode of action of these two peptides may be through similar pathways (i.e. calcium channels, calcium antagonist, serotonin receptor block, dopamine D2 receptor block). The clustering of two peptides with behavioural impacts from neuroactive drugs presents clear and surprising additional evidence for the potential of therapeutically-relevant peptide-host interactions (Figure 4). The behavioural impacts of the other peptides are distinct from the neuroactive drugs tested, yet clustered, which may reflect the testing methods such as bacterial growth conditions and timings, and method of peptide delivery. Example 5 - Peptide SEQ ID No: 1 and peptide SEQ ID No: 48 influence features related to worm area, speed, and / or angular velocity The specific behavioural features affected by each of the 66 peptides are diverse; the inventors focused on peptide with amino acid: SEQ ID No: 1; DNA: SEQ ID No: 67 and peptide with amino acid: SEQ ID No: 48; DNA: SEQ ID No: 114 for illustrative purposes. The behavioural features affected by peptide SEQ ID No: 1 were primarily associated with angular velocity, area, and speed, and those affected by peptide SEQ ID No: 48 were associated with area. Feature scores for representative features from each of these categories are illustrated in Figure 6. Summary The human gut microbiome is central to human health, development, and disease. Gut microbes can modulate various key aspects of physiology and behaviour via the gut-brain-axis, a bidirectional signalling pathway that facilitates fundamental physiological processes, but is also linked to a multitude of diseases. Proteins derived from bacteria can mimic human peptide neurotransmitters and peptide hormones, which have important roles in the gut- brain-axis. In addition, these proteins may also have distinct mechanisms of action, and not just mimic human neurotransmitters and hormones. The inventors have discovered 66 peptides with evidence of potential neuromodulatory activity based on quantifiable modulation of C. elegans behavioural features. The results from multiple independent behavioural screens in C. elegans worms, as discussed in Examples 1-2, provide evidence that bacterial peptides derived from the gut microbiome modulate their host via the gut-brain-axis. In addition, through the utilisation of bioinformatic approaches, the inventors have identified peptides, within those encoded by SEQ ID No: 1-66, to contain domains with previously documented interaction with the host, including a CxxC thioredoxin-like motif and an AgrD domain. Furthermore, the behavioural impacts of two of the 66 peptides (i.e. SEQ ID No: 1 and SEQ ID No: 48) cluster with previously observed responses to the therapeutic drugs Mebeverine hydrochloride, Flunarizine dihydrochloride, and Clomiphene citrate, suggesting that these two peptides would induce a phenotype that shares similarities with responses to the aforementioned drug cluster. The clustering of these peptides with behavioural impacts from neuroactive drugs presents clear and surprising additional evidence for the potential of therapeutically-relevant peptide-host interactions. The neuromodulatory activity of these peptides could therefore be harnessed in a therapeutic context for diseases caused by, or associated with, the gut-brain- axis. References Azarnia Tehran, D. A., Pirazzini, M., Leka, O., Mattarei, A., Lista, F., Binz, T., Rossetto, O., and Montecucco, C. (2017) Hsp90 is involved in the entry of clostridial neurotoxins into the cytosol of nerve terminals, Cellular Microbiology, 19: e12647. doi: I.L., Feriani, L., Minga, E. et al. Megapixel camera arrays enable high-resolution animal tracking in multiwell plates. Commun Biol 5, 253 (2022). https: / / doi.org / 10.1038 / s42003-022-03206-1 Breton J, Tennoune N, Lucas N, Francois M, Legrand R, Jacquemot J, Goichon A, Guérin C, Peltier J, Pestel-Caron M, Chan P, Vaudry D, do Rego JC, Liénard F, Pénicaud L, Fioramonti X, Ebenezer IS, Hökfelt T, Déchelotte P, Fetissov SO. Gut Commensal E. coli Proteins Activate Host Satiety Pathways following Nutrient-Induced Bacterial Growth. Cell Metab.2016 Feb 9;23(2):324-34. doi: 10.1016 / j.cmet.2015.10.017. Epub 2015 Nov 24. PMID: 26621107. Cornell R, Cao W, Harradine B, Godini R, Handley A, Pocock R. Neuro-intestinal acetylcholine signalling regulates the mitochondrial stress response in Caenorhabditis elegans. Nat Commun. 2024.15;6594. https: / / doi.org / 10.1038 / s41467-024-50973-y Ericson MD, Schnell SM, Freeman KT, Haskell-Luevano C. A fragment of the Escherichia coli ClpB heat-shock protein is a micromolar melanocortin 1 receptor agonist. Bioorg Med Chem Lett.2015 Nov 15;25(22):5306-8. doi: 10.1016 / j.bmcl.2015.09.046. Epub 2015 Sep 21. PMID: 26433448; PMCID: PMC4628882. Lerch J.K., Puga D.A., Bloom O., Popovich P.G. Glucocorticoids and macrophage migration inhibitory factor (MIF) are neuroendocrine modulators of inflammation and neuropathic pain after spinal cord injury. Semin. Immunol.2014;26(5):409–414. doi: 10.1016 / j.smim.2014.03.004 Liu C, Khan A, Seban N, Littlejohn N, Shah A, Crinivasan S. A homeostatic gut-to-brain insulin antagonist restrains neuronally stimulated fat loss. Nat Comm.2024.15:6869. Mahoney TR, Luo S, Round EK, Brauner M, Gottschalk A, Thomas JH, Nonet ML. Intestinal signaling to GABAergic neurons regulates a rhythmic behavior in Caenorhabditis elegans.2008. 105(42);16350-16355. https: / / doi.org / 10.1073 / pnas.0803617105 O’Brien TJ, Barlow IL, Feriani L, Brown AEX. Systematic creation and phenotyping of Mendelian disease models in C. elegans: towards large-scale drug repurposing. eLife.2023.12:RP92491. doi: https: / / doi.org / 10.7554 / eLife.92491.1.sa3 Pirazzini, M., Montecucco, C. & Rossetto, O. Toxicology and pharmacology of botulinum and tetanus neurotoxins: an update. Arch Toxicol 96, 1521–1539 (2022). https: / / doi.org / 10.1007 / s00204-022-03271-9 Nguyen MT, Beck J, Lue H, Fünfzig H, Kleemann R, Koolwijk P, Kapurniotu A, Bernhagen J. A 16- residue peptide fragment of macrophage migration inhibitory factor, MIF-(50-65), exhibits redox activity and has MIF-like biological functions. J Biol Chem.2003 Sep 5;278(36):33654-71. doi: 10.1074 / jbc.M301735200. Epub 2003 Jun 9. PMID: 12796500. Patten SA, Aggad D. et al. Neuroleptics as therapeutic compounds stabilizing neuromuscular transmission in amyotrophic lateral sclerosis. JCI insight.2017; 2(22):e97152. Sberro H, Fremin BJ, Zlitni S, Edfors F, Greenfield N, Snyder MP, Pavlopoulos GA, Kyrpides NC, Bhatt AS. Large-Scale Analyses of Human Microbiomes Reveal Thousands of Small, Novel Genes. Cell.2019 Aug 22;178(5):1245-1259.e14. doi: 10.1016 / j.cell.2019.07.016. Epub 2019 Aug 8. PMID: 31402174; PMCID: PMC6764417. Tennoune N, Chan P, Breton J, Legrand R, Chabane YN, Akkermann K, Järv A, Ouelaa W, Takagi K, Ghouzali I, Francois M, Lucas N, Bole-Feysot C, Pestel-Caron M, do Rego JC, Vaudry D, Harro J, Dé E, Déchelotte P, Fetissov SO. Bacterial ClpB heat-shock protein, an antigen-mimetic of the anorexigenic peptide α-MSH, at the origin of eating disorders. Transl Psychiatry.2014 Oct 7;4(10):e458. doi: 10.1038 / tp.2014.98. PMID: 25290265; PMCID: PMC4350527. Wang H, Girskis K, Janssen T, Chan JP, Dasgupta K, Knowles JA, Schoofs L, Sieburth D. 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Claims

Claims 1. A peptide comprising an amino acid sequence substantially as set out as SEQ ID No: 38, 33, 59, 58, 43, 1-32, 34-37, 39-42, 44-57, 60-66, or a variant or fragment thereof, or a nucleic acid encoding one or more of the peptide, or a variant or fragment thereof, for use in therapy.

2. A peptide comprising an amino acid sequence substantially as set out as SEQ ID No: 38, 33, 59, 58, 43, 1-32, 34-37, 39-42, 44-57, 60-66, or a variant or fragment thereof, or a nucleic acid encoding one or more of the peptide, or a variant or fragment thereof, for use in treating, preventing, or ameliorating a disease caused by, or associated with, the gut-brain-axis.

3. A peptide for use according to any preceding claim, wherein an anatomical target site of the peptide comprising an amino acid sequence substantially as set out as SEQ ID No: 38, 33, 59, 58, 43, 1-32, 34-37, 39-42, 44-57, 60-66, or a variant or fragment thereof, or a nucleic acid encoding one or more of the peptide, or a variant or fragment thereof, is selected from a group of target sites consisting of: the gastrointestinal tract (including enteroendocrine cells, immune cells, epithelial cells, enteric neurons, smooth muscle cells, interstitial cells of Cajal, enterochromaffin cells); the peripheral nervous system (including dorsal root ganglia, sympathetic and parasympathetic arms of the autonomic nervous system, enteric nervous system, or vagus nerve); the central nervous system; the neuroendocrine system; the neuroimmune system; the hypothalamic- pituitary-adrenal axis; and the gut microbiota.

4. A peptide for use according to any preceding claim, wherein the disease entails an effect on general physiological and / or homeostatic roles, which is selected from a group of roles consisting of: satiety; food intake; glucose regulation; fat metabolism; insulin secretion; intestinal motility; blood flow; secretion and absorption by the gut; normal digestion; hormone secretion; GPCR stimulation (e.g. TGR5, GPR40, GPR119, SSTR5, CCKa, PDE4, or DPP-4); release of neurotransmitters (e.g. GLP-1, GLP2, GIP, PYY, or CCK); metabolic and oxidative stress; inflammation (e.g., via vagus nerve); stimulation ofautoantigens; mood; fear; temperament; cognition; memory; sociability; and aging.

5. A peptide for use according to any preceding claim, wherein the disease to be treated is selected from a group of diseases caused by, or associated with, the gut-brain-axis, consisting of: neurodegenerative diseases; central nervous system disorders; metabolic disorders; autoimmune and inflammatory disorders; gut barrier dysfunction; and functional gastrointestinal disorders.

6. A peptide for use according to claim 5, wherein the neurodegenerative disease is selected from a group of neurodegenerative diseases consisting of: Alzheimer's disease (including Benson's syndrome); Parkinson's disease (including progressive supranuclear palsy, Steele-Richardson-Olszewski syndrome, normal pressure hydrocephalus, vascular or arteriosclerotic parkinsonism, or drug-induced parkinsonism); dementia (including Lewy Body dementia, vascular dementia, or frontotemporal dementia); episodic cluster headache; migraine; pain; multiple sclerosis; Huntington's disease; amyotrophic lateral sclerosis; Lou Gehrig's disease; motor neuron disease; prion disease; spinocerebellar ataxia; spinal muscular atrophy; primary progressive aphasia; mild cognitive impairment; HIV-related cognitive impairment; progressive inflammatory neuropathy; and corticobasal degeneration.

7. A peptide for use according claim 5, wherein the central nervous system disorder is selected from a group of central nervous system disorders consisting of: mood disorders; anxiety; depression; affective disorders; schizophrenia; malaise; cognition disorders; addiction; autism; and epilepsy.

8. A peptide for use according to claim 5, wherein the metabolic disorder is selected from a group of metabolic disorders consisting of: diabetes (and complications, such as diabetic nephropathy, diabetic retinopathy, or diabetic neuropathy); cardiovascular disease; metabolic syndrome; obesity; dyslipidaemia; non-alcoholic fatty liver disease and non-alcoholic steatohepatitis.

9. A peptide for use according to claim 5, wherein the nutritional disorder is selected from a group of nutritional disorders consisting of: hyperphagia; cachexia; anorexia nervosa; short bowel syndrome; intestinal failure; intestinal insufficiency; and eating disorders.

10. A peptide for use according to claim 5, wherein the inflammatory and / or autoimmune disorder is selected from a group of inflammatory and / or autoimmune disorders consisting of: inflammatory bowel disease; ulcerative colitis; Crohn's disease; psoriasis; coeliac disease; and arthritis.

11. A peptide for use according to claim 5, wherein the gut barrier dysfunction is selected from a group of gut barrier dysfunctions consisting of: environmental enteric dysfunction; and spontaneous bacterial peritonitis.

12. A peptide for use according to claim 5, wherein the functional gastrointestinal disorder is selected from a group of functional gastrointestinal disorders consisting of: irritable bowel syndrome; functional dyspepsia; functional abdominal bloating / distension; functional diarrhoea; functional constipation; and opioids-induced constipation.

13. A peptide for use according to any preceding claim, wherein the disease is selected from a group of other diseases consisting of: enteritis (chemotherapy- induced, radiation-induced); necrotising enterocolitis; gastrointestinal injury (toxic, radiation, chemotherapy); gastroparesis; nausea; and vomiting.

14. A peptide for use according to any preceding claim, wherein the nucleic acid sequence comprises a nucleotide sequence substantially as set out in any of SEQ ID No: 67-132, or a variant or fragment thereof.

15. A peptide for use according to any preceding claim, wherein the peptide comprises an amino acid sequence substantially as set out as SEQ ID No: 133- 187, or a variant or fragment thereof, or a nucleic acid encoding one or more of the peptide, or a variant or fragment thereof.

16. A peptide for use according to claim 15, wherein the nucleic acid comprises a nucleotide sequence which encodes any one of the peptides of SEQ ID No: 133-187 or a variant or fragment thereof.

17. A peptide for use according to any preceding claim, wherein the peptide comprises: a CxxC-motif containing thioredoxin-superfamily-like domain; an AgrD domain; a DUF3789 domain; an SCIFF domain; or a Target ACGX domain.

18. A pharmaceutical composition for treating, preventing or ameliorating a disease, that is caused by, or associated with, the gut-brain-axis, comprising a therapeutically effective amount of a peptide comprising an amino acid sequence substantially as set out in SEQ ID No: 38, 33, 59, 58, 43, 1-32, 34-37, 39-42, 44-57, 60-66, or a variant or fragment thereof, or a nucleic acid encoding one or more of the peptide, or variant or fragment thereof, and a pharmaceutically acceptable vehicle.

19. A process for making the pharmaceutical composition according to claim 18, the process comprising combining a therapeutically effective amount of a peptide comprising an amino acid sequence substantially as set out in SEQ ID No: 38, 33, 59, 58, 43, 1-32, 34-37, 39-42, 44-57, 60-66, or a variant or fragment thereof, or a nucleic acid encoding one or more of the peptide, or variant or fragment thereof with a pharmaceutically acceptable vehicle.

20. The composition according to claim 18, or the process according to claim 19, wherein the peptide, nucleic acid or disease is as defined in any one of claims 1-17.

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