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Long chain dicarboxylic fatty acid (LCDFA) producing microbes and uses thereof
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A technology of microorganism and fatty acid metabolism, applied in the field of microorganisms producing long-chain dicarboxy fatty acids (LCDFA) and their uses
Pending Publication Date: 2021-01-29
医学生命探索有限公司
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[0003] Despite overwhelming evidence linking gastrointestinal cancers to chronic inflammation, all focus on early detection of cancers such as colorectal cancer has focused exclusively on improving detection of tumor-derived markers or premalignant lesions, with no underlying metabolic or inflammatory risk factors for
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[0324] 1. Identification of gut microbes associated with GTA levels
[0325] METHODS: High-throughput amplicon sequencing of the microbial V4 variable region of the microbial 16S rRNA gene was performed on total DNA extracted from 405 human colonic mucosa and fecal samples using an Illumina Miseq instrument. The data for each sample were rarefied to 8700 total sequences. Operational taxonomic units (OTUs) were filtered by percentage of total and the top 90% were selected for comparison with serum GTA levels. Serum levels of 35 GTAs in the same subjects were determined by flow injection tandem mass spectrometry. GTA levels were then aligned to sequence data at OUT levels, followed by quintile analysis based on GTA levels to identify statistically significantly different OTUs between the highest and lowest GTA quintiles.
[0326] RESULTS: A comparison of OTUs between the lowest and highest serum GTA quintiles in multiple GTAs revealed significant differences (p
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Abstract
A method for increasing gastric tract acid (GTA) production in a mammalian subject. The method comprises administering a therapeutically-effective amount of a composition comprising at least one liveor attenuated culture of a microbial species selected from the genus Blautia, species Faecalibacterium prausnitzii, genus Bacteroides, family Ruminococcaceae, family Lachnospiraceae, genus Coprococcus, genus Roseburia, genus Oscillospira, species Ruminococcus bromii, genus Ruminococcus, family Costridiaceae, species Dorea formicigenerans, species Bacteroides uniformis, genus Dorea, genus Streptococcus, order Clostridiales, genus Anaerostipes, genus Dialister, species Bifidobacterium adolescentis, family Coriobacteriaceae, genus Faecalibacterium, genus Sutterella, species Bacteroides ovatus, genus Parabacteroides, genus Ruminococcus, species Bacteroides faecis, species Eubacterium biforme, genus Phascolartobacterium, and family Enterobacteriaceae; or a prebiotic composition which increasesgrowth and / or viability of said microbial species in the gut. Administering the composition increases the synthesis of at least one GTA dicarboxylic fatty acid metabolite in said subject. Also described are method for determining gastrointestinal inflammation status and kits for detecting and treating a gastric tract acid (GTA) insufficiency.
Description
technical field [0001] The present invention relates to the treatment of gastrointestinal inflammation and gastric tract acid (GTA) long-chain fatty acid deficiency by manipulating the gut microbiome. The present invention also relates to compositions and methods for increasing gastric acid (GTA) production in a mammalian subject. Background technique [0002] Chronic inflammation is widely recognized as a major underlying cause of gastrointestinal (GI) cancers, including colorectal, pancreatic, gastric, esophageal, ovarian, and others (Marusawa and Jenkins 2014; Hussain and Harris 2007; Chapkin, McMurray, and Lupton, 2007; Demaria et al., 2010; Itzkowitz and Yio, 2004; Maccio and Madeddu, 2012; Schwartsburd, 2004; Terzic et al., 2010; Wu et al., 2014). Chronic inflammation can lead to oxidative stress, which in turn can lead to oncogenic events as well as genetic mutations that drive malignant transformation of cells (Mannick et al. and Zhang et al.). Cancer growth is sub...
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