Role of Akkermansia muciniphila in nonalcoholic fatty liver disease / 临床肝胆病杂志

Nonalcoholic fatty liver disease （NAFLD） has become the most common chronic liver disease in the world， and it is also one of the main causes of liver cirrhosis and hepatocellular carcinoma， so it is particularly important to curb the development and progression of NAFLD in a timely manner. However， due to its complex pathogeneses， there are currently no effective methods for radical treatment. As a new generation of probiotics， Akkermansia muciniphila （Akk bacteria） can improve metabolic disorders of the body， and more and more studies have shown that Akk bacteria have a potential therapeutic effect on metabolic diseases， especially NAFLD. Therefore， this article briefly reviews the mechanism of action of Akk bacteria in NAFLD， in order to provide new ideas for improving the treatment of NAFLD and creating new therapies.

Research Progress on Role of Probiotic Akkermansia Muciniphila in Oncogenesis, Development and Treatment of Tumor / 肿瘤防治研究

Although tumor treatment models have been continuously improved in clinical practice, cancer remains a serious threat to human health. The effect of probiotics on tumor therapy has received extensive attention. As a common colonizer of the intestinal mucosa, Akkermansia muciniphila(AKK) has a well-defined role in metabolic diseases, but its complex role in tumor development and therapeutic efficacy has not been fully elucidated. The unique properties and physiological roles of AKK play an important role in different solid tumors and it may be a potential biomarker. This article provides a review of previous studies and proposes clinical strategies to influence the abundance of AKK to provide a theoretical reference for the development of next-generation probiotics and the reshaping of the tumor treatment landscape.

Effects of Akkermansia on AOM/DSS Inflammatory-associated Colorectal Cancer / 肿瘤防治研究

Objective To investigate the effects of Akkermansia muciniphila (AKK) on azomethane-oxide (AOM)/glucan sodium sulfate (DSS)-induced inflammatory colorectal cancer mouse model and intestinal stem cells. Methods AOM/DSS-induced mouse models of inflammatory-associated colorectal cancer were randomly divided into three groups, namely, model, AKK and aspirin groups, based on different administration of drugs by gavage. The tumor number, size, distribution, and burden were observed 10 weeks after intervention. Immunohistochemical method was used to analyze the expressions of Ki67 and Lgr5 proteins, which are utilized to characterize tumor malignancy and stem cells. The mRNA expressions of Lgr5, CD133, Nanog, and ALDH1 were detected by qRT-PCR. Results Compared with those of the model group, the tumor number, size, and burden of the AKK group were significantly reduced (P < 0.01). The expressions of Ki67 and Lgr5 in the AKK group of tumor tissues were significantly decreased (P < 0.05), and the mRNA expressions of CD133, Nanog and ALDH1 were significantly down-regulated. Conclusion AKK is effective against AOM/DSS-induced colitis-associated colorectal cancer in mice, and its mechanism of action may be closely related to colorectal stem cell activity.

Akkermansia Muciniphila Suppresses Non-alcoholic Steatohepatitis-associated Liver Cancer in Mice by Recovering Intestinal Barrier Function / 肿瘤防治研究

Objective To investigate whether the next-generation probiotics Akkermansia muciniphila can prevent non-alcoholic steatohepatitis (NASH)-related hepatocellular carcinoma (HCC). Methods We constructed a NASH-HCC model called STAM. STAM mice received oral saline or A. muciniphila starting at 4 weeks of age. Liver tissues were evaluated by HE staining and oil red O staining for NASH activity, and intrahepatic expression levels of inflammatory cytokines and ileal tight junction proteins were measured by RT-PCR. Results At 8 weeks of age, the steatosis, ballooning degeneration and NAS scores, TNF-α, MCP-1, IL-1β, and IL-6 mRNA expression were significantly decreased in the STAM+A. muciniphila group (both P < 0.05) compared with those in the STAM+saline group (all P < 0.05). At 20 weeks of age, the number of liver surface tumors formed, tumor size and IL-6 level were decreased in the STAM + A. muciniphila group (all P < 0.05). A. muciniphila restored the thickness of the colon mucosal layer and the number of goblet cells in STAM mice as well as increased the mRNA expression of the tight junction proteins ZO-1, Claudin-3, and Occludin in ileal epithelial cells. Conclusion Akkermansia muciniphila can inhibit the progression of NASH to HCC by improving the intestinal barrier function and may serve as a candidate drug to prevent NASH-HCC.

Dihydroartemisinin increased the abundance of Akkermansia muciniphila by YAP1 depression that sensitizes hepatocellular carcinoma to anti-PD-1 immunotherapy / 医学前沿

The effect of anti-programmed cell death 1 (anti-PD-1) immunotherapy is limited in patients with hepatocellular carcinoma (HCC). Yes-associated protein 1 (YAP1) expression increased in liver tumor cells in early HCC, and Akkermansia muciniphila abundance decreased in the colon. The response to anti-PD-1 treatment is associated with A. muciniphila abundance in many tumors. However, the interaction between A. muciniphila abundance and YAP1 expression remains unclear in HCC. Here, anti-PD-1 treatment decreased A. muciniphila abundance in the colon, but increased YAP1 expression in the tumor cells by mice with liver tumors in situ. Mechanistically, hepatocyte-specific Yap1 knockout (Yap1LKO) maintained bile acid homeostasis in the liver, resulting in an increased abundance of A. muciniphila in the colon. Yap1 knockout enhanced anti-PD-1 efficacy. Therefore, YAP1 inhibition is a potential target for increasing A. muciniphila abundance to promote anti-PD-1 efficacy in liver tumors. Dihydroartemisinin (DHA), acting as YAP1 inhibitor, increased A. muciniphila abundance to sensitize anti-PD-1 therapy. A. muciniphila by gavage increased the number and activation of CD8+ T cells in liver tumor niches during DHA treatment or combination with anti-PD-1. Our findings suggested that the combination anti-PD-1 with DHA is an effective strategy for liver tumor treatment.

Akkermansia Muciniphila Alleviates Visceral Hypersensitivity in Irritable Bowel Syndrome Rats via Regulating CB2R / 中山大学学报(医学科学版)

ObjectiveTo investigate the mechanism of Akkermansia muciniphila （A. muciniphila） regulating the visceral hypersensitivity in irritable bowel syndrome （IBS） rats induced by neonatal maternal separation （MS） and water avoidance stress （WAS）. MethodsNeonatal male Sprague-Dawley rats were randomly divided into sham WAS group （blank group）， MS+WAS group （IBS model group） and A. muciniphila group. IBS model was established by MS combined with WAS in both IBS model group and A. muciniphila group. Meanwhile， the rats in the A. muciniphila group were given 1 mL 1×109 CFU/mL A. muciniphila by gavage daily for 10 days. Visceral pain responses were detected by behavioral observations and abdominal withdrawal reflex scores. ResultsCompared with IBS model group， A. muciniphila group exhibited significant increase of body weight and visceral pain threshold， significantly decreased numbers of fecal particles and proportions of unformed stools， significantly higher expression levels of cannabinoid receptor type 2 （CB2R） mRNA in colon tissues. ConclusionA. muciniphila may alleviate the visceral hypersensitivity in IBS rats by regulating the expression of CB2R mRNA in colonic tissues.

Xinhui citrus fermentation liquor ameliorates acute ulcerative colitis in mice via regulating intestinal bacteria homeostasis and Nrf2/NLRP3 pathway to repair intestinal mucosa / 药学学报

This study investigated the protective effect and related mechanisms of Xinhui citrus fermentation liquor on mice with ulcerative colitis. Animal experiments follow the rules of Animal Ethics Committee of Southern Medical University. C57BL/6 mice were given 3% dextran sodium sulfate (DSS) for 6 days to induce acute ulcerative colitis. During this period, Xinhui citrus fermentation liquor, decoction of Citrus reticulata blanco (both orally administrated with 300 mg·kg-1·d-1 crude polysaccharide) or positive drug 5-aminosalicylic acid (100 mg·kg-1·d-1) were gavaged continuously for 9 days. Cecal contents were collected for 16S rRNA sequencing analysis. The levels of inflammatory factors, tight junction proteins and nuclear factor erythroid 2 related factor 2 / Nod-like receptor protein 3 (Nrf2/NLRP3) pathway related proteins in the colon were detected by real-time PCR (RT-PCR), immunofluorescence and Western blot. Our results showed that Xinhui citrus fermentation liquor and Citrus reticulata blanco protected against UC-induced weight loss, diarrhea, bloody stool, and colon shortening. The mRNA and protein levels of pro-inflammatory factors, such as interleukin 6 (Il-6) and CXC chemokine ligand 10 (Cxcl10) and NLRP3 inflammasome were significantly decreased; the mRNA levels of colon anti-inflammatory factor (Il-10), tight junction protein [zonula occludens-1 (Zo-1), occludin, claudin-1], mucin 2 (Muc2), Nrf2, as well as the mRNA and protein levels of NAD(P)H quinine oxidoreductase 1 (NQO1) and heme oxygenase 1 (HO-1) were significantly increased. In addition, Xinhui citrus fermentation liquor increased the abundance of Akkermansia and reduced the abundance of harmful bacteria Enterococcus and Streptococcus. The correlation analysis showed that the abundance of Akkermansia was positively correlated with anti-inflammatory factors, tight junction protein and the related genes levels of Nrf2 signaling pathway. In summary, Xinhui citrus fermentation liquor ameliorates acute ulcerative colitis in mice via regulating intestinal bacteria homeostasis and Nrf2/NLRP3 pathway to repair intestinal mucosa.

Mechanism study of Si Miao Formula on alleviating insulin resistance by increasing the abundance of Akkermansia muciniphila in mice / 药学学报

In our previous study, we found that Si Miao Formula (SMF) had the effect of improving the disorder of glucose metabolism caused by high fat and high sucrose diet, and significantly altered the composition of gut microbiota, especially increasing the level of Akkermansia muciniphila (A. muciniphila). However, it is unclear that the role of intestinal flora and A. muciniphila play in SMF improving blood glucose homeostasis, and the mechanism of how SMF increases the level of A. muciniphila. Therefore, this study will explore the correlation between SMF improving the insulin resistance and increasing the level of A. muciniphila, as well as the mechanism of SMF-induced growth of A. muciniphila using the in vitro and in vivo experiments. We explored the effect of intestinal flora and A. muciniphila on SMF-improved insulin resistance through fecal microbiota transplantation (FMT) and antibiotic intervention. In order to study the mechanisms underlying SMF on elevating A. muciniphila, we disassembled SMF to find the key component which can particularly elevate the number of A. muciniphila. Using the in vitro anaerobic culture system combined with cell and animal experiments, we explored the mechanism of the key component in elevating A. muciniphila. The research was approved by the Animal Ethical and Welfare Committee of Shanghai University of Traditional Chinese Medicine. Our results showed that the gut microbiota altered by SMF can improve high fat and sucrose diet induced insulin resistance in recipient mice, and the improvement was closely related to the abundance of A. muciniphila. Cortex Phellodendri played the most important role in regulating the composition of intestinal flora and increasing the number of A. muciniphila, of which, berberine was the key component of Cortex Phellodendri which up regulated A. muciniphila. We have found that berberine cannot directly promote the growth of A. muciniphila in vitro, but it can stimulate the expression of mucin, which, in turn, promote the growth of A. muciniphila. The above results show that the improved insulin sensitiviy by SMF depends on the increased level of A. muciniphila. The effect of SMF on elevating the amount of A. muciniphila might be correlated with the increased expression of mucin stimulated by berberine.

Review of literature on Akkermansia muciniphila and its possible role in the Etiopathogenesis and Therapy of Type 2 Diabetes Mellitus / Journal of the ASEAN Federation of Endocrine Societies

@#Akkermansia muciniphila is a promising gut microbiota for the treatment of type 2 diabetes mellitus (T2DM). A. muciniphilastimulates intestinal wall integrity, is an anti-inflammatory agent, and reduces endoplasmic reticulum stress, lipogenesis and gluconeogenesis. These properties make A. muciniphila a potential treatment option for T2DM by reducing insulin resistance and increasing insulin sensitivity and glucose tolerance in different tissues. This article explores the possible role of A. muciniphila in T2DM management, along with the various methods known to modulate A. muciniphila.

Distributions of gut Akkermansia muciniphila and its non-linear associations with obesity / 中华内分泌代谢杂志

Objective:Investigating the distribution of intestinal Akkermansia muciniphila (AKK) and explore abundance-effect in obesity obesity to provide potential dose effect for obesity intervention.Methods:Clinical data of 6 986 subjects including body mass index, waist circumference, and common confounders such as gender, age, diastolic blood pressure, systolic blood pressure, fasting blood glucose, triglyceride, total cholesterol, high density lipoprotein-cholesterol, low density lipoprotein-cholesterol, and uric acid were collected from Guangdong Gut Microbiome Project in 2008. 16S ribosomal RNA (16S rRNA) sequencing data were used to estimate the genus abundance of AKK as well as its operational taxonomic unites (OTUs). Central obesity and overall obesity were diagnosed according to the criteria of China Obesity Working Group in 2002. Multivariate logistic regression was used to analyze the OR (95% CI) of obesity with one-unite elevation of AKK. The dose effect of AKK on obesity was estimated by comparing the trend of ORs from the 1st to the 20th quantile. Results:A total of three AKK OTUs(AKK OTU1, AKK OTU2, AKK OTU3) were identified: AKK OTU1 and AKK OTU2 were distributed in more than 90% of the population, while AKK OTU3 was distributed at 21.7%; All the OTUs showed a"bimodal"distributional pattern and their correlations with common factors were variable. Disparities of the association with obesity were found between the OTUs and the AKK. AKK OTU1, AKK OTU2, and the genus level of AKK showed significant protective effects against obesity; The ORs (95% CI) were 0.95(0.93-0.98), 0.97(0.94-0.99), 0.93(0.91-0.96), respectively for central obesity; And ORs(95% CI) were 0.88(0.80-0.97), 0.98(0.93-1.02), 0.81(0.74-0.89), respectively for overall obesity. The results were similar after adjustment for common confounders. According to the calculation of dose-effect, the protect effects of AKK increased with accumulated abundance and the minimum effective dose on central obesity and overall obesity was 1.83% and 4.98%, respectively. Conclusion:AKK is a protective factor for obesity, but the dose-effect of AKK and the strain-differences should be considered in the future interventional study.

Advances of Akkermansia muciniphila in regulating host functions / 中国中药杂志

Akkermansia muciniphila, abbreviated as AKK and found in 2004, is an oval-shaped gram-negative bacterium isolated from a human feal. A. muciniphila is widely present in the intestinal tract of human. Its specialization in mucin degradation makes it a key organism at the mucosal interface between the lumen and host cells. More and more studies have shown that it can play the role of probiotics. Notably, declined levels of A. muciniphila have been observed in patients with diabetes, liver disease, cardiovascular disease, inflammatory bowel disease, neurodegenerative diseases, etc. In addition, A. muciniphila combined with traditional Chinese medicine, exhibited higher effect on regulating host functions, but the underlying mechanism was still unclear, requiring further in-depth research. Therefore, the aims of this review are to summarize the main effects of A. muciniphila on host health and its relationship with traditional Chinese medicine, summarize the main problems, and provide a reference for the further research of A. muciniphila and traditional Chinese medicine.

Study results of the composition of oral microflora in Mongolian patients with Behcet’s disease / Шинэ санаа Шинэ нээлт

Purpose@#Behcet’s disease is characterized by repeated acute inflammatory attacks with aphthous ulcers of the oral mucosa, uveitis of the eyes, skin symptoms, and genital ulcers. Although its etiology is still unknown, there is evidence of the involvement of oral bacteria in systemic diseases. Various types of oral bacteria may be involved in the development and progression of Behcet's disease. Therefore, the present study investigated alterations in the oral flora of patients with Behcet’s disease in Mongolia. We collected saliva samples from the Mongolian Behcet's disease (BD) group and healthy control (HC) group, and the oral flora were analyzed using next generation sequencer (NGS).@*Methods@#DNA was extracted from the unstimulated saliva samples from the 47 BD and 48 HC subjects. The DNA was amplified from the V3-V4 region of 16S rRNA using PCR, and the data were acquired using NGS. Based on the obtained data, we analyzed the alpha diversity, beta diversity, and bacterial taxonomy of the salivary flora.</br> Household survey covered 148 people with visual and hearing impairments to assess social service accessibility.@*Results@#Beta diversity differed significantly between the BD and HC flora, but no significant differences were observed in alpha diversity. We found that the proportions of three genera—an S24-7 family unknown species, a mitochondria family unknown species, and Akkermansia species were significantly lower in the BD than in the HC group.@*Conclusion@#The reduced proportions of the S24-7 family and symbiotic Akkermansia species may be key phenomena in the oral flora of patients with BD.

Role of Akkermansia muciniphila in Intestinal Diseases and Prospect of Microflora Therapy / 胃肠病学

Akkermansia muciniphila, a bacterium colonizing the intestinal mucous layer, affects the human intestinal environment. The abundance of Akkermansia muciniphila decreased in metabolic diseases such as obesity and diabetes, and the abundances of Akkermansia muciniphila in intestinal diseases such as irritable bowel syndrome, inflammatory bowel disease and intestinal tumors are varied. This article reviewed the effect of Akkermansia muciniphila on intestinal diseases and prospect of microflora therapy.

Research advances in Akkermansia muciniphila and liver injury / 临床肝胆病杂志

Liver injury caused by viral and non-viral factors is an important stage of chronic liver disease, and the pathogenesis of liver injury is still a research hotspot. With the deepening of the research on gut microbiota, substantial evidence indicates that gut microbiota participates in the development and progression of liver injury, and it has been confirmed that Akkermansia muciniphila (Akk) has a beneficial effect against liver injury. This article summarizes the role and potential mechanism of Akk in immune-mediated liver injury, alcoholic liver disease, and nonalcoholic fatty liver disease. It is believed that Akk may provide new directions and choices for the prevention and treatment of liver injury.

Effects of probiotics and prebiotics on intestinal microbiota in mice with acute colitis based on 16S rRNA gene sequencing / 中华医学杂志(英文版)

Background@#Imbalance of intestinal microbiota was closely related to colitis. Under these circumstances, regulation of enteric flora may be beneficial to the repair of inflammation. We aimed to investigate the effects of probiotics (Bifidobacterium and Lactobacillus), prebiotics and their combination on inflammation, and microflora in mice of acute colitis.@*Methods@#C57BL/6J mice were divided into six groups randomly (blank control group, model control group, probiotics group, synbiotics group, lactitol group and probiotics + lactitol group). Each group was given 2.5% dextran sulfate sodium drinking water for 5 days other than the blank control group. Except for the model control group, the other four groups were intervened with probiotics, synbiotics (probiotics and inulin), lactitol, and probiotics + lactitol. Mice were sacrificed after 1 week of gavage, and pathologic scores were calculated. The feces of different periods and intestinal mucosa samples were collected to analyze the differences of intestinal microbiota by 16S rRNA sequencing. Differences of two groups or multiple groups were statistically examined through unpaired Student t test and analysis of variance (ANOVA), respectively. ANOVA, Tukey, Anosim, and metastats analysis were used to compare differences of microbiota among different groups.@*Results@#After gavage for 1 week, the pathologic scores of groups with the intervention were significantly lower than those in the model control group, and the difference was statistically significant (P < 0.05). The model control group was higher in the genus of Bacteroides (relative abundance: 0.3679 vs. 0.0099, P = 0.0016) and lower in Lactobacillus (relative abundance: 0.0020 vs. 0.0122, P = 0.0188), Roseburia (relative abundance: 0.0004 vs. 0.0109, P = 0.0157), compared with the blank control group. However, the same phenomenon was not found in groups gavaged with probiotics and lactitol. Compared with model control group, mice with intervention were increased with Bifidobacterium (relative abundance: 0.0172 vs. 0.0039, P = 0.0139), Lachnospiraceae_NK4A136_group (relative abundance: 0.1139 vs. 0.0320, P = 0.0344), Lachnospiraceae_UCG-006 (relative abundance: 0.0432 vs. 0.0054, P = 0.0454), and decreased with Alistipes (relative abundance: 0.0036 vs. 0.0105, P = 0.0207) in varying degrees. The mucosal flora was more abundant than the fecal flora, and genus of Mucispirillum (relative abundance: 0.0207 vs. 0.0001, P = 0.0034) was more common in the mucosa. Lactitol group showed higher level of Akkermansia than model control group (relative abundance: 0.0138 vs. 0.0055, P = 0.0415), probiotics group (relative abundance: 0.0138 vs. 0.0022, P = 0.0041), and synbiotics group (relative abundance: 0.0138 vs. 0.0011, P = 0.0034), while probiotics + lactitol group had more abundant Akkermansia than synbiotics group (relative abundance: 0.0215 vs. 0.0013, P = 0.0315).@*Conclusions@#Probiotics and prebiotics reduce the degree of inflammation in acute colitis mice obviously. Mice with acute colitis show reduced beneficial genera and increased harmful genera. Supplementation of probiotics and prebiotics display the advantage of increasing the proportion of helpful bacteria and regulating the balance of intestinal microbiota. Lactitol might promote the proliferation of Akkermansia.

Research progress on Akkermansia muciniphila in human intestine / 中华临床感染病杂志

Recent studies heve demonstrated that Akkermansia muciniphila (A.muciniphila) plays an important role in human health and disease , including regulating the development of the immune system and the metabolic phenotype of the host.This article reviews the research progress on A.muciniphila in recent years, focusing on the basic characteristics , the influencing factors of colonization , and the underlying mechanism of maintaining intestinal homeostasis of A.muciniphila.Additionally, the article summarizes the potential association between A.muciniphila and the chronic metabolic diseases such as obesity , atherosclerosis,diabetes mellitus and infectious diseases.The perspect of A.muciniphila as a new generation of probiotics in clinical medicine and the challenge for its industrialization are also discussed in the article .

Relationship between akkermansia muciniphila and obesity / 第二军医大学学报

Akkermansia muciniphila (A. muciniphila) is a normal flora of human gastrointestinal tract. The A. muciniphila abundance of intestinal flora in obese patients is significantly decreased. Many evidences suggest that A. muciniphila is negatively related to obesity, diabetes, cardiovascular diseases and low-grade inflammation. A. muciniphila not only plays a metabolic protective role by protecting the integrity of intestinal epithelial cells and mucus layer, but also plays an anti-inflammatory role by regulatory T cells, endogenous cannabinoid system and non-classical Toll-like receptor in the process of inflammatory reaction. This article reviews the relationship between A. muciniphila and obesity, and the molecular mechanism and application of A. muciniphila in obesity.

Therapeutic perspectives of intestinal probiotics A. muciniphila in metabolic disorders / 药学学报

italic>Akkermansia muciniphila (A. muciniphila) is an intestinal bacterium that was isolated from human feces in 2004. Its specialization in mucin degradation makes it a key organism that maintains the intestinal mucosal barrier function. A. muciniphila, which is the only representative of the Verrucomicrobia that can be cultured, is relatively easy to be detected in metagenomic analysis. For the past few years, A. muciniphila has quickly attracted the attention of researchers and become a medical and biological hotspot due to the close correlation between its intestinal colonization and the development and progression of various metabolic diseases. This review introduces the biological characteristics and colonization environment of A. muciniphila, and reviews its relationship with host health and disease, especially focusing on the metabolic disease and related mechanism, as well as the factors affecting its colonization in the host, expecting to provide evidence and clues for drug development targeting A. muciniphila.

Effects of lactitol on the intestinal microbiota in mice by 16S rRNA sequencing / 中华消化杂志

Objective@#To investigate the effects of probiotics, lactitol of different concentrations, and their combination on intestinal microbiota in mice. @*Methods@#Fifty C57BL/6J mice were divided into blank control group, probiotics group, lactitol of standard concentration group, lactitol of high concentration group, and combination of probiotics and lactitol group, 10 mice in each group, with no intervention, gavaged with 1×109 colony-forming units(CFU)/d probiotics, with lactitol of standard concentration (6.6 g·kg-1·d-1), with lactitol of high concentration (10.0 g·kg-1·d-1), with probiotics (5×108 CFU/d) and lactitol (3.3 g·kg-1·d-1) for two weeks, respectively. The feces before gavage and one week and two weeks after gavage were collected. And intestinal mucosa samples were also collected at two weeks after gavage for 16S rRNA sequencing. Alpha diversity analysis, principal component analysis (PCA) and taxonomy were used for analysis of the changes of microbiota. @*Results@#The results of alpha diversity analysis showed there was no statistically significant difference in feces between before gavage and at one week after gavage (P=0.552, 0.062). The results of alpha diversity analysis and PCA indicated that there was no statistically significant difference in intestinal microbiota between lactitol of standard concentration group and lactitol of high concentration group (P=0.270 and 0.085). One week and two weeks after gavage, compared lactitol of standard concentration group and lactitol of high concentration group with blank control group and probiotics group, Akkermansia in feces both increased (one week after gavage, 0.114 3 vs. 0.003 9 and 0.013 1, 0.071 3 vs. 0.003 9 and 0.013 1; P<0.01, P=0.001 and P=0.001, 0.005; two weeks after gavage, which was 0.094 0 vs. 0.030 5 and 0.018 9, 0.142 4 vs. 0.030 5 and 0.018 9; P=0.044, 0.016 and 0.001, <0.01). Compared combination of probiotics and lactitol group with lactitol of standard concentration group and high concentration group, Bacteroides in feces increased (one week after gavage, 0.115 9 vs. 0.037 5 and 0.041 6, P=0.013 and 0.015; two weeks after gavage, 0.058 0 vs. 0.023 2 and 0.014 4, P=0.047 and 0.009). The increase of Lachnospiraceae appeared earlier in combination of probiotics and lactitol group (at one week after gavage). Two weeks after gavage, compared with that of blank control group, lactitol of standard concentration group and high concentration group, Lachnospiraceae in feces of probiotics group increased (all P<0.05). Compared with that of probiotics group, Akkermansia of mucosa in lactitol of standard concentration group increased (0.018 0 vs. 0.001 8, P=0.012). Akkermansia of mucosa in lactitol of high concentration group also increased compared with that of blank control group and probiotics group (0.037 0 vs. 0.010 0 and 0.001 8, P=0.002, <0.01). Comparing combination of probiotics and lactitol group with blank control group, lactitol of standard concentration group and lactitol of high concentration group, and comparing probiotics group with lactitol of high concentration group, Mucispirillum in mucosa all increased (0.040 0 vs. 0.014 8, 0.013 7 and 0.009 9, 0.019 6 vs. 0.009 9; P=0.041, 0.040, 0.018 and 0.011). @*Conclusions@#Supplementary probiotics, lactitol and combination of them all have obvious regulative role in mucosal flora of mice. Exogenous probiotics can not easily colonized in the intestine. Lactitol can obviously promote the proliferation of Akkermansia in feces and intestine.

Research progress on relationship of Akkermansia muciniphila and type 2 diabetes mellitus and intervention effects of Chinese materia medica / 中草药

Akkermansia muciniphila planted at the end of ileum and on the outer layer of intestinal grume for colon and cecum is a kind of dominant bacteria using mucoproteins as the culture medium. On the one hand, it can provide energy to degrade mucoprotein for protection of epithelial cell of intestinal mucosa and decline the permeability of mucosal barrier. On the other hand, it can preferentially use the mucoprotein. As known to all, excessive abundance will weaken the mucosal barrier and the occurrence and development of type 2 diabetes is closely related to the long-term chronic low-intensity inflammatory reaction arising from the damage of intestinal barrier function. Therefore, to improve the intestinal flora and protect intestinal mucosal barrier, A. muciniphila has served as a new idea to treat type 2 diabetes. As A. muciniphila is the dominant bacteria on the outer layer of intestinal mucosa closely relevant to the intestinal mucosal barrier function, this article has reviewed its physiological property and its role in curing type 2 diabetes.