Bacillus coagulans for regulating and controlling host stress defense and delaying senescence and application thereof

Abstract

The invention discloses bacillus coagulans for regulating and controlling host stress defense and delaying senescence and application of the bacillus coagulans, and belongs to the field of microorganisms. The invention provides a new application of the bacillus coagulans CCFM1041 in the aspects of delaying senescence and regulating intestinal flora, and model organisms and clinical experiments prove that the strain can realize senescence intervention, which is specifically reflected as follows: (1) the life expectancy of an individual is remarkably prolonged, the resistance of a host to environmental stress such as heat stress is improved, and the anti-aging effect of the host is improved; the motor function decline related to aging is improved; (2) regulating and controlling the intestinal microecological balance, specifically increasing the abundance of beneficial bacteria (such as bifidobacteria and lactobacillus), inhibiting the proliferation of potential pathogenic bacteria and reducing the age of the intestinal tract, thereby delaying the aging process of the intestinal flora. The invention provides a new application of the bacillus coagulans CCFM1041, and provides a new thought in the aspect of development of anti-aging drugs or microecologics.

Description

Technical Field

[0001] The invention relates to Bacillus coagulans capable of regulating host stress defense and delaying aging and application thereof, and belongs to the field of microorganisms. Background Art

[0002] The intestinal flora, also known as the gut microbiota or gut microbiome, refers to the vast array of microorganisms that inhabit the intestines of humans and other animals. These microorganisms primarily include bacteria, fungi, viruses, archaea, and other microorganisms, which far outnumber the body's own cells. Bacteria are the most numerous of the intestinal microbiome, accounting for over 99% of the total intestinal microbiome. These include the Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria. Gut microorganisms play an important role in breaking down food and synthesizing vitamins and other bioactive substances. With aging, the composition and function of the intestinal microbiome may change, affecting nutrient absorption and metabolism, and in turn, overall health and physiological function. The intestinal microbiome is also closely linked to the immune system. A healthy intestinal flora promotes the normal functioning of the immune system, while an imbalanced intestinal flora can lead to a decline in immune system function, making people more susceptible to disease and thus exacerbating intestinal aging.

[0003] As the "third genome", the dynamic composition of the intestinal microbiome is significantly correlated with the host's aging process. Studies have found that the intestinal flora of centenarians presents youthful characteristics (dominated by the genus Bacteroides, high flora diversity, and low abundance of pathogenic bacteria), and their intestinal age / physiological age ratio is lower than that of the general elderly population. Intestinal age is usually used to characterize the degree of intestinal aging, mainly referring to the balance of various bacteria in the intestine. It is the "third age" in addition to psychological age and physiological age, reflecting the degree of aging or functional status of the intestine. There are significant individual differences between physiological age and intestinal age. Some young groups may show a higher intestinal age. This premature intestinal aging feature often indicates that their intestinal microecological balance is disturbed and the mucosal barrier function is weakened. A younger intestinal age may have better digestion and absorption function, lower inflammation levels and a healthier microbial environment. On the contrary, an older bacterial age may be associated with an increased risk of chronic diseases, inflammation, metabolic disorders and other diseases. Patent CN114093515A discloses an age prediction method based on ensemble learning of intestinal flora prediction models. By integrating intestinal microbiome metagenomic data and adjusting for host confounding factors, this method can be used to accurately and individually assess the extent of intestinal aging. Furthermore, Caenorhabditis elegans (C. elegans) has become a classic model for anti-aging research due to its short lifespan (approximately 20 days), well-defined aging-related genes (such as daf-2 / age-1), and highly conserved IIS signaling pathway.

[0004] Modern lifestyles (such as a high-fat, low-fiber diet and the abuse of antibiotics) lead to a decrease in the diversity of intestinal flora, and the proliferation of pathogenic bacteria produces endotoxins such as lipopolysaccharide (LPS). These toxins enter the blood circulation through the damaged intestinal barrier, activate the NF-κB pathway to trigger chronic low-grade inflammation, and inhibit the AMPK-mTOR autophagy pathway, leading to cell clearance dysfunction. Clinical data show that the intestinal age deviation of people with premature intestinal aging is positively correlated with the incidence of metabolic syndrome. Probiotics, as a type of active microorganisms that are beneficial to the host (such as humans or animals), can regulate the dynamic balance of intestinal flora when consumed in sufficient amounts, which is closely related to systemic aging.

[0005] Bacillus coagulans is a novel probiotic with the ability to form spores. Its core advantage as a probiotic lies in its ability to withstand the erosion of gastric acid and bile, allowing it to survive and function in the intestines. However, the functional performance of probiotics is significantly strain-specific, and the specific health effects of different Bacillus coagulans strains on the human body still require in-depth verification through extensive clinical trials. Currently, there are no patents related to this bacterium's ability to regulate intestinal flora structure and delay intestinal aging. The development of Bacillus coagulans probiotic preparations with clear efficacy has become a technical direction that urgently needs breakthroughs. Summary of the Invention

[0006] The present invention provides the use of Bacillus coagulans CCFM1041 in preparing multi-dimensional anti-aging and / or intestinal flora regulating products; the Bacillus coagulans CCFM1041 was deposited in the Guangdong Provincial Microbiological Culture Collection Center on January 18, 2019, with the deposit number GDMCC No. 60538, and was disclosed in the patent application document with publication number CN114908023A.

[0007] In one embodiment, the product comprises food, medicine, feed or pet food.

[0008] In one embodiment, the pet includes, but is not limited to, a canine, feline, small mammal, aquatic, avian, reptile, or insect pet.

[0009] In one embodiment, the multi-dimensional anti-aging includes one or more of the following: extending individual life expectancy, enhancing individual heat stress tolerance, and improving aging-related motor behavior disorders.

[0010] In one embodiment, regulating the intestinal flora includes increasing the number of one or more beneficial bacteria in the intestine, including Bifidobacterium animalis, Bifidobacterium bifidum, Lactobacillus reuteri, Lactobacillus plantarum, and Anaerobutyricum_hallii, and / or reducing the number of harmful bacteria such as Clostridium portoli.

[0011] In one embodiment, the anti-aging also includes reducing intestinal age and delaying intestinal function aging.

[0012] In one embodiment, the product comprises a microbial preparation comprising the Bacillus coagulans CCFM1041.

[0013] In one embodiment, the microbial agent comprises a liquid preparation, a semisolid preparation or a solid preparation.

[0014] In one embodiment, the microbial preparation contains prebiotics.

[0015] In one embodiment, the prebiotics include but are not limited to a combination of one or more of fructooligosaccharides, inulin, xylo-oligosaccharides, galacto-oligosaccharides, and stachyose.

[0016] In one embodiment, the prebiotics may include one or more of fructooligosaccharides, inulin, xylooligosaccharides, galacto-oligosaccharides and stachyose, and the content of the prebiotics accounts for 25% to 80% of the mass of the microbial preparation.

[0017] In one embodiment, the microbial preparation further contains maltodextrin and / or red raspberry juice powder.

[0018] In one embodiment, the solid preparation contains viable bacteria ≥ 2.5×10 9 CFU / g of Bacillus coagulans CCFM1041.

[0019] Beneficial effects

[0020] The present invention relates to a strain of Bacillus coagulans CCFM1041 with multi-dimensional anti-aging functions and its applications. The strain achieves aging intervention through the following synergistic mechanisms:

[0021] (1) Significantly extend the lifespan of model organisms, enhance the host's resistance to environmental stresses such as heat stress, and improve aging-related motor function decline;

[0022] (2) Regulate the balance of intestinal microecology in the human body, specifically increase the abundance of beneficial bacteria (such as Bifidobacterium animalis, Bifidobacterium bifidum, Lactobacillus reuteri, Lactobacillus plantarum, and Anaerobutyricum_hallii), inhibit the proliferation of potential pathogenic bacteria (such as Clostridium boulardii), reduce intestinal age, and thus delay the aging process of intestinal flora;

[0023] This invention reveals for the first time the synergistic anti-aging effects of Bacillus coagulans CCFM1041 through multiple pathways, including enhancing stress defense, maintaining motor function, and reshaping intestinal flora, providing a new technical solution for the development of microecological preparations such as anti-aging foods, medicines, feed, and pet food. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 Effect of feeding Bacillus coagulans CCFM1041 on the lifespan of nematodes.

[0025] Figure 2 Effect of feeding Bacillus coagulans CCFM1041 on the ability of nematodes to resist heat stress.

[0026] Figure 3 Effect of feeding Bacillus coagulans CCFM1041 on the motility of nematodes.

[0027] Figure 4 PCOA diagram of the effect of taking Bacillus coagulans CCFM1041 on the β-diversity of human intestinal flora.

[0028] Figure 5 Bar graph showing the effects of Bacillus coagulans CCFM1041 on the phylum levels of human intestinal flora.

[0029] Figure 6 Bar graph showing the effects of taking Bacillus coagulans CCFM1041 on the species level of human intestinal flora.

[0030] Figure 7 Lefse analysis of the effect of taking Bacillus coagulans CCFM1041 on the species level of human intestinal flora. DETAILED DESCRIPTION

[0031] The present invention is further described in detail below by way of examples. These examples are only used to illustrate the present invention and are not intended to limit the scope of the present invention.

[0032] Strains:

[0033] Bacillus coagulans CCFM1041 has been disclosed in patent application publication number CN114908023A; Bacillus coagulans VNJBGZ3 and Bacillus coagulans VNJBGZ9 are strains isolated from the same source as Bacillus coagulans CCFM1041.

[0034] Culture medium:

[0035] MRS liquid medium (g / L): peptone 10 g / L, yeast extract 5 g / L, glucose 20 g / L, anhydrous sodium acetate 2 g / L, diammonium hydrogen citrate 2 g / L, dimethyl phosphate trihydrate 2.6 g / L, magnesium sulfate heptahydrate 0.5 g / L, manganese sulfate heptahydrate 0.25 g / L, Tween-80 1 g / L, distilled water 1000 g / L.

[0036] MRS solid medium (g / L): peptone 10 g / L, yeast extract 5 g / L, glucose 20 g / L, anhydrous sodium acetate 2 g / L, diammonium hydrogen citrate 2 g / L, dimethyl phosphate trihydrate 2.6 g / L, magnesium sulfate heptahydrate 0.5 g / L, manganese sulfate heptahydrate 0.25 g / L, Tween-80 1 g / L, agar 20 g / L, distilled water 1000 g / L.

[0037] M9 buffer (g / L): sodium chloride 5 g / L, potassium dihydrogen phosphate 3 g / L, sodium hydrogen phosphate 3.1 g / L, magnesium sulfate heptahydrate 0.246 g / L. LNGM solid medium (g / L): sodium chloride 3 g / L, agar 17 g / L, peptone 2.5 g / L, calcium chloride 0.111 g / L, magnesium sulfate heptahydrate 0.246 g / L, potassium dihydrogen phosphate 2.710 g / L, potassium hydrogen phosphate 0.89 g / L, cholesterol 5 mg / L.

[0038] NGM-FUDR modified solid medium (g / L): sodium chloride 3 g / L, agar 17 g / L, peptone 2.5 g / L, calcium chloride 0.111 g / L, magnesium sulfate heptahydrate 0.246 g / L, potassium dihydrogen phosphate 2.710 g / L, potassium hydrogen phosphate 0.89 g / L, cholesterol 5 mg / L, 5-fluoro-2'-deoxyuridine 24.6 mg / L.

[0039] Spore-forming medium (g / L): yeast extract 0.7 g / L, peptone 1 g / L, glucose 1 g / L, ammonium sulfate 0.2 g / L, magnesium sulfate heptahydrate 0.2 g / L, potassium dihydrogen phosphate 1 g / L.

[0040] The reagents used in the present invention are all commonly used reagents and can be purchased from conventional reagent production and sales companies.

[0041] Example 1: Evaluation of the effect of Bacillus coagulans CCFM1041 on extending the lifespan of Caenorhabditis elegans

[0042] (1) Experimental model and grouping

[0043] Caenorhabditis elegans, with its well-defined genetic background and aging pathways, simple structure, and short lifespan, is considered a standard model for aging research. To eliminate strain-specific interference, homologously isolated Bacillus coagulans VNJBGZ3 and VNJBGZ9 were used as control strains in this example to ensure rigorous efficacy evaluation.

[0044] (2) Nematode synchronization process

[0045] 1. Thaw N2 nematodes frozen at -80°C, centrifuge at 300 × g for 2 min to remove the freezing solution, transfer to NGM plates pre-cultured with E. coli OP50, and place in a 20°C incubator for passage (3 days / generation);

[0046] 2. After passage three times, the adult worms were collected by washing with M9 buffer and digested with nematode lysis buffer (M9 buffer: 5% sodium hypochlorite: 1 mol / L sodium hydroxide = 2:1:2 v / v) until only a few worms remained.

[0047] 3. Centrifuge at 6000 × g for 2 min, discard the supernatant, and repeat the washing process until there is no irritating odor. Finally, add an appropriate amount of M9 buffer to resuspend the suspension and culture at 20°C for 12 h to obtain synchronized L1 larvae.

[0048] 4. The synchronized L1 larvae were centrifuged at 300 × g for 2 min, the supernatant was removed, and the larvae were transferred to a new NGM plate pre-cultured with OP50. The plates were then cultured in a 20°C incubator for 48 h to obtain synchronized L4 nematodes.

[0049] (3) Lifespan experiment plan

[0050] L4-stage nematodes (n = 30 / group) were plated on NGM-FUDR medium containing Bacillus coagulans CCFM1041, VNJBGZ3, or VNJBGZ9, respectively. The experiment was maintained at a constant temperature of 20°C, with the medium changed every 48 hours and survival recorded. Death was determined when pharyngeal suction ceased or when the nematode showed no response to gentle mechanical stimulation with the platinum wire of the worm teaser. Nematodes accidentally lost, injured by organ crushing, or injured during transfer were not counted in lifespan statistics.

[0051] (4) Data analysis methods

[0052] Survival curves were analyzed using the Gehan-Breslow-Wilcoxon test. Lifespan data are presented as mean ± standard deviation (mean ± SD). Differences between groups were assessed using a two-sided t-test. Experiments were repeated three times and visualization was performed using GraphPad Prism 8.0. In the figures, asterisks indicate statistically significant differences (*: P < 0.05; **: P < 0.01; ***: P < 0.001).

[0053] like Figure 1 As shown in Figure 2, CCFM1041 can significantly prolong the lifespan of C. elegans. Compared with the VNJBGZ3 group, the survival curve of nematodes fed with Bacillus coagulans CCFM1041 shifted significantly to the right (P<0.001, Figure 1 a), the average lifespan was extended by 70.6% to 8.1 days (P<0.01, Figure 1 b); Compared with the VNJBGZ9 group, the survival curve of nematodes fed with Bacillus coagulans CCFM1041 shifted to the right, which was statistically significant (P<0.05, Figure 1 c), the average lifespan increased by 20.9% to 3.4 days (P<0.05, Figure 1 d).

[0054] Example 2: Verification of the effect of Bacillus coagulans CCFM1041 on enhancing the heat stress resistance of nematodes

[0055] The host aging process is closely related to stress resistance. Stress resistance in nematodes is a key hallmark of aging, reflecting their ability to survive environmental stress. This experiment, based on the synchronized L4 nematode model described in Example 1, employed a 34°C heat stress regime to evaluate the regulatory effects of CCFM1041 on the host's stress defense system.

[0056] 50 L4 stage nematodes prepared by the method of Example 1 were picked and transferred to the plate coated with 40 μL (final concentration of 1×10 9 CFU / mL) of Bacillus coagulans CCFM1041, Bacillus coagulans VNJBGZ3, and Bacillus coagulans VNJBGZ9 were cultured on NGM-FUDR modified solid medium, which was replaced every two days. After eight days of culture, the culture medium was placed in a 34°C biochemical incubator for heat stress. Nematode survival was counted every two hours until all nematodes died. Death was determined using the same criteria as in Example 1.

[0057] The data analysis method is the same as in Example 1, and the results are as follows Figure 2As shown in the results, Bacillus coagulans CCFM1041 significantly improved the heat stress resistance of nematodes. Compared with the VNJBGZ3 group, the survival curve of nematodes fed with Bacillus coagulans CCFM1041 shifted to the right by 103.6% (P<0.0001, Figure 2 a), the survival time was prolonged by 3.86 h (P<0.001, Figure 2 b); Compared with the VNJBGZ9 group, the survival curve of the Bacillus coagulans CCFM1041 group showed significant differences (P<0.01, Figure 2 c), the survival time increased by 43.7% and the life span was extended by 2.13 h (P < 0.001, Figure 2 d).

[0058] Example 3: Verification of the effect of Bacillus coagulans CCFM1041 on improving the motor function of Caenorhabditis elegans

[0059] Muscle degeneration is a core phenotype of aging, and the rate of muscle frequency decay can quantitatively reflect the aging state. This study evaluated the protective effects of Bacillus coagulans CCFM1041 on the muscle-nerve system by quantifying the nematode worm's oscillation frequency.

[0060] 20 L4 stage nematodes prepared according to the method of Example 1 were picked and transferred to the plate coated with 40 μL (final concentration of 1×10 9 CFU / mL) of Bacillus coagulans CCFM1041, Bacillus coagulans VNJBGZ3, and Bacillus coagulans VNJBGZ9 were cultured on NGM-FUDR-modified solid medium, which was replaced every two days. After eight days of culture, the test nematodes were placed in M9 buffer and allowed to acclimate freely. Each complete wiggle of the nematode's head or tail was counted as a wiggle. After acclimating for 30 seconds, the number of wiggles per minute was recorded.

[0061] The data analysis method is the same as in Example 1, and the results are as follows Figure 3 As shown in Figure 2, compared with the VNJBGZ3 group, the swing frequency of nematodes fed with Bacillus coagulans CCFM1041 increased by 11.3% (P < 0.05, Figure 3 a). Compared with the VNJBGZ9 group, the worm swing frequency of the nematodes fed with Bacillus coagulans CCFM1041 increased by 15.5% (P<0.05, Figure 3 b).

[0062] Example 4 Preparation of Bacillus coagulans CCFM1041 microbial agent

[0063] The preparation of the microbial preparation strip pack in this embodiment includes the following technical steps:

[0064] The freeze-dried powder of Bacillus coagulans CCFM1041 and prebiotics are mixed evenly, and maltodextrin and red raspberry juice powder are optionally added. The mixture is filled to obtain a probiotic strip package containing Bacillus coagulans, each package containing 2g; wherein the prebiotics may include one or more of fructooligosaccharides, inulin, xylo-oligosaccharides, galacto-oligosaccharides, and stachyose, and the amount of prebiotics added is 0.5g to 1.6g per package; and the number of viable bacteria of Bacillus coagulans CCFM1041 is 2.5×10 9 CFU.

[0065] Example 5: Verification of the Effect of Bacillus coagulans CCFM1041 Microbial Preparation on Regulating Intestinal Flora and Reducing Intestinal Age

[0066] 1. Human fecal collection and metagenomic testing

[0067] Twenty subjects were recruited. They had not taken any laxatives or probiotics in the past two weeks. After signing the informed consent form, stool sampling cups were distributed to the subjects, who collected stool to determine their baseline intestinal age.

[0068] The probiotics were administered in the form of probiotic powder. The probiotic powder was prepared according to the method of Example 4, and each piece (2 g) contained 2.5×10 9 CFU, and 0.5g xylo-oligosaccharide.

[0069] Probiotic powder can be taken directly or with warm water (not exceeding 37°C). The dosage of probiotics is 2 pieces / day (i.e. 5×10 9 CFU / day), taken half an hour to one hour after a meal. During these two weeks, the subjects maintained a regular schedule, ate a normal diet, avoided major mood swings, did not take any medications or other probiotic products (including yogurt and probiotic drinks), and had no other diseases (such as colds). Two weeks later, stool samples from these 20 subjects were collected again. In the laboratory, genomic DNA was extracted from the 40 stool samples collected above, the extracted DNA was fragmented, and a metagenomic library was constructed. The library was sequenced using high-throughput sequencing technology to obtain the original metagenomic data of the samples.

[0070] 2. Bioinformatics analysis

[0071] Raw metagenomic data from 20 subjects were quality-controlled using FastQC (version 0.11.9). Low-quality sequences were filtered and removed using Trimmomatic 0.39 software. The average base quality within a sliding window of 4 base pairs starting from the 5' end of the sequence was calculated, with an average quality of 25 used as the trimming threshold. Sequences greater than 60 base pairs were retained as quality-control output. Next, the filtered sequences were aligned to the human reference genome (Homo sapiens genome assembly GRCh38, hg38) using Bowtie2 2.4.4, samtools 1.15, and bedtools 2.30.0 to remove host-derived genes present in the samples. Species and functional annotations were performed on the high-quality sequences after quality control using MetaPhlAn3 and HUMAnN3. Finally, intestinal age was calculated for all samples using an age prediction model (disclosed in patent application publication number CN114093515A).

[0072] 3. The results show that:

[0073] (1) Effect of Bacillus coagulans CCFM1041 on intestinal flora diversity

[0074] Figure 4 The results showed that after taking the Bacillus coagulans CCFM1041 probiotic preparation for 2 weeks, the intestinal flora composition of the subjects had a significant shift compared with two weeks ago (p-value: 0.012), indicating that Bacillus coagulans CCFM1041 played a role in regulating intestinal flora.

[0075] (2) Effects of Bacillus coagulans CCFM1041 on intestinal flora composition

[0076] Figure 5 It showed that after taking Bacillus coagulans CCFM1041 for two weeks, the abundance of Firmicutes and Actinobacteria in the subjects' intestines increased significantly, while the abundance of Proteobacteria decreased significantly. In the intestinal microbiota, Firmicutes is one of the main bacterial phyla, which is closely related to the host's energy metabolism, immune regulation and intestinal health. Actinobacteria are a type of Gram-positive bacteria that can produce a variety of metabolites that are beneficial to humans, such as antibiotics and enzymes. The Proteobacteria include many pathogens, such as Escherichia coli, Salmonella, Vibrio cholerae, Helicobacter pylori and other well-known species.

[0077] Figure 6 and Figure 7The results showed that further analysis of the species-level composition and lefse of the intestinal flora showed that after taking the probiotic preparation for 2 weeks, the abundance of Bifidobacterium and Lactobacillus in the subjects' intestines increased significantly. Among them, the Bifidobacterium species with significantly increased abundance were mainly Bifidobacterium animalis and Bifidobacterium bifidum. In clinical studies, certain strains of Bifidobacterium animalis showed resistance to acid and oxidative stress, which can accelerate human intestinal transit and provide symptom relief for individuals with common gastrointestinal symptoms, irritable bowel syndrome and constipation. Bifidobacterium bifidum has many potential benefits for health, especially in the digestive system and the overall immune system. It may help reduce intestinal inflammation and may be beneficial for the treatment of inflammatory bowel diseases such as Crohn's disease and ulcerative colitis. The lactic acid bacteria with significantly increased abundance were Lactobacillus reuteri and Lactobacillus plantarum. Lactobacillus reuteri has multiple health benefits, including regulating inflammatory bowel disease, promoting digestion and absorption, and relieving constipation. At the same time, Lactobacillus plantarum is also a beneficial bacterium with multiple health benefits, including regulating immune function, regulating chronic metabolic diseases, antagonizing pathogenic bacterial infections, regulating intestinal function, and regulating mental and neurological functions. In addition, taking CCFM1041 can significantly increase the relative abundance of Anaerobutyricum hallii in the human intestine. Previously known as Eubacterium hallii, many studies have shown that Anaerobutyricum hallii may play an important role in human intestinal health and disease prevention, especially in metabolic regulation and reducing the toxicity of carcinogens in food. It is considered a potential beneficial microorganism, or the next generation of probiotics. On the other hand, we also found that the abundance of Enterococcus bolteae, which is believed to be related to human diseases such as autism spectrum disorder, was significantly reduced after taking CCFM1041.

[0078] In summary, Bacillus coagulans CCFM1041 has the effect of increasing the number of beneficial bacteria in the human intestine and reducing the abundance of harmful bacteria.

[0079] (3) Effect of Bacillus coagulans CCFM1041 on the age of intestinal flora

[0080] As shown in Table 1, the intestinal age of the subjects before and after taking Bacillus coagulans CCFM1041 was calculated and compared using the age prediction model. It was found that 17 out of 20 subjects had a significant decrease in intestinal age after taking CCFM1041, and the average intestinal age was significantly reduced from 60.93±1.90 years before taking it to 58.95±2.06 years after taking it (p-value: 0.003).

[0081] Table 1: Effects of Bacillus coagulans CCFM1041 on human intestinal age

[0082] serial number Age before taking (years) Intestinal age after taking (years) Changes in intestinal age (years) Changes in intestinal age (%) A1 61.75 61.10 -0.65 -1.1％ A2 62.58 59.07 -3.51 -5.6％ A3 60.80 56.74 -4.06 -6.7％ A4 62.45 58.83 -3.63 -5.8％ A5 58.57 58.85 0.28 0.5％ A6 61.96 58.93 -3.03 -4.9％ A7 62.55 60.77 -1.78 -2.8％ A8 63.32 63.25 -0.07 -0.1％ A9 59.97 59.05 -0.92 -1.5％ A10 57.18 56.34 -0.83 -1.5％ A11 59.41 58.45 -0.95 -1.6％ A12 61.85 61.22 -0.63 -1.0％ A13 64.09 57.27 -6.83 -10.7％ A14 57.77 58.53 0.76 1.3％ A15 63.70 54.70 -9.00 -14.1％ A16 59.38 59.23 -0.15 -0.3％ A17 60.81 58.48 -2.33 -3.8％ A18 59.81 58.32 -1.49 -2.5％ A19 61.03 62.84 1.81 3.0％ A20 59.66 56.98 -2.68 -4.5％

[0083] Although the present invention has been disclosed above in terms of preferred embodiments, it is not intended to limit the present invention. Anyone familiar with this technology can make various changes and modifications without departing from the spirit and scope of the present invention. Therefore, the scope of protection of the present invention should be based on the definition of the claims.

Claims

1. Application of Bacillus coagulans CCFM1041 in the preparation of multi-dimensional anti-aging and / or intestinal flora regulating products, characterized in that: The deposit number of the Bacillus coagulans CCFM1041 is GDMCC No.60538.

2. The use according to claim 1, characterized in that The product includes food, medicine, feed or pet food.

3. The use according to claim 2, characterized in that The pets include, but are not limited to, dogs, cats, small mammals, aquatic animals, birds, reptiles, or insect pets.

4. The use according to any one of claims 1 to 3, characterized in that: The multi-dimensional anti-aging includes one or more of the following: extending individual life expectancy, enhancing individual heat stress tolerance, and improving aging-related motor behavior disorders.

5. The use according to any one of claims 1 to 3, characterized in that: The regulating intestinal flora includes increasing the number of one or more beneficial bacteria selected from Bifidobacterium animalis, Bifidobacterium bifidum, Lactobacillus reuteri, Lactobacillus plantarum, and Anaerobutyricum_hallii in the intestine, and / or reducing the number of Clostridium portlandii.

6. The use according to any one of claims 1 to 5, characterized in that: The anti-aging also includes reducing the age of the intestine and delaying the aging of intestinal function.

7. The use according to any one of claims 1 to 5, characterized in that: The product is a microbial preparation containing Bacillus coagulans CCFM1041.

8. The use according to claim 7, characterized in that The microbial agent is a liquid preparation, a semisolid preparation or a solid preparation.

9. The use according to claim 7 or 8, characterized in that The microbial preparation contains prebiotics; the prebiotics include but are not limited to a combination of one or more of fructooligosaccharides, inulin, xylooligosaccharides, galacto-oligosaccharides and stachyose.

10. The use according to claim 8 or 9, characterized in that: The solid preparation contains viable bacteria ≥ 2.5×10 9 CFU / g of Bacillus coagulans CCFM1041.

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