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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.
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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.
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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.
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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.
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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.
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@#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.
Subject(s)
Gastrointestinal Microbiome , Insulin Resistance , Probiotics , Diabetes Mellitus, Type 2ABSTRACT
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.
Subject(s)
Humans , Akkermansia , Inflammatory Bowel Diseases , Intestines , Probiotics , Verrucomicrobia/geneticsABSTRACT
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.
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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.
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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.
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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 .
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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.
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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.