Aging is commonly associated with chronic inflammation, which also is the main hallmark and risk factor of hyperglycemia and IR with the development of age [128]. Sign up below to be the first to receive latest product updates and special offers only to those on this list! Within this microbiome are thousands of different species of bacteria. This mucus layer plays an important role in protecting the intestinal epithelial cells (layer of cells that lines the internal surface of the intestine (7). Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. A recent report found that Akk significantly increases thermogenesis and GLP-1 secretion in HFD-induced C57BL/6J obese mice by induction of uncoupling protein 1 (UCP1) in brown adipose tissue and systemic GLP-1 secretion [36]. do not necessarily reflect the official policy or position of the host. Wang B., Chen X., Chen Z., Xiao H., Dong J., Li Y., Zeng X., Liu J., Wan G., Fan S., et al. A metagenome-wide association study of gut microbiota in type 2 diabetes. Powerful sources of polyphenols include berries, fresh herbs, real cranberry juice, and cocoa. The above results suggest that Akk ameliorates aging and aging-associated metabolic disorders by regulating host immunity and recovering gut microbiota homeostasis mediated by elevating Akk abundance and its metabolites including butyrate, secondary bile acids, and GABA, which suggests that Akk may be a potential aging therapy strategy, although it still warrants more investigations and clinical trials to test this (Figure 3). As explained above, Akk can ameliorate gut barrier impairment in the cases of obesity [22,39,40,47], metabolic diseases [71,76,85], inflammation [85,122,123], and aging [125,129,130,131,132]; therefore, it is necessary to know how Akk interacts with the host intestinal barrier. Global scientific output trend for Akkermansia muciniphila research: A bibliometric and scientometric analysis. Apart from using mucin as a carbon and nitrogen source, alive Akk also improves the metabolic profile and mucus layer thickness, whereas heat-killed Akk fails to do so [47]. Commentary: Dietary Polyphenols Promote Growth of the Gut Bacterium Akkermansia muciniphila and Attenuate High-Fat Diet-Induced Metabolic Syndrome. Mok K.C., Sokolovskaya O.M., Nicolas A.M., Hallberg Z.F., Deutschbauer A., Carlson H.K., Taga M.E. As previously mentioned, the relative abundance of Akk is reduced in HCC model mice, and continuous treatment with Akk restores the diversity of gut microbiota and reduces liver injury, inflammation, and fibrosis [82]. Akk also inhibits gut Ruminococcus torque, decreases serum endotoxin levels, and downregulates TLR expression, eventually promoting regulatory immunity and delaying the development of diabetes [59]. Physiological character and components of Akkermansia muciniphila. Ottman N., Reunanen J., Meijerink M., Pietil T.E., Kainulainen V., Klievink J., Huuskonen L., Aalvink S., Skurnik M., Boeren S., et al. The current results imply that the dual effects of Akk on rodents and humans are contradictory and warrant further investigations to evaluate its dose, safety, and toxicity in humans. Furthermore, an 84 kDa purified P9 protein secreted by Akk alone was sufficient to induce GLP-1 secretion and brown adipose tissue thermogenesis by interacting with ICAM-2, whereas IL-6 deficiency abrogated the effects of P9 on glucose homeostasis and downregulated ICAM-2 expression [36]. Join new and get your free copy of Paleolicious Snack Ideas. -Derived Extracellular Vesicles as a Mucosal Delivery Vector for Amelioration of Obesity in Mice. The critical contributions of Akk toward human metabolic health have just begun to be elucidated. Akk treatment ameliorates ALS by promoting the production of nicotinamide in the central nervous system of Sod1-Tg mice. After washed microbiota transplantation (WMT) treatment, more than half of patients achieved clinical responses and significantly increased colonization rates of Akk compared to pre-WMT, which is closely corrected with the efficacy of WMT for IBD [105]. Compared with Akk, EVs derived from Akk induce a more significant loss in body and fat weight in HFD-fed mice [39]. Compared with patients with obesity or asthma, patients with obese asthma usually display additive effects, with higher proinflammatory signatures and changes in the composition of the microbiota, and their asthma disease severity is negatively correlated with fecal Akk level [54]. Ouwerkerk JP, Aalvink S, Belzer C, De Vos WM. Thursby E., Juge N. Introduction to the human gut microbiota. However, most of the current researches focus on the correlation between A. muciniphila and diseases, and little is known about the causal relationship between them. population in the gut microbiota of mice. Bian X., Wu W., Yang L., Lv L., Wang Q., Li Y., Ye J., Fang D., Wu J., Jiang X., et al. National Library of Medicine induces intestinal adaptive immune responses during homeostasis. 2023 Jan;107(1):1-8. doi: 10.1007/s00253-022-12305-2. The genome of Akkermansia muciniphila, a dedicated intestinal mucin degrader, and its use in exploring intestinal metagenomes. 2023 Jill Carnahan. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Prebiotics in the diet such as the fructooligosaccharides found in MegaPre, and in anti-inflammatory polyphenols found in berries, grapes, and cranberry, like those found in Cran-Max, are known to preferentially support and maintain A. muciniphila levels. In this enlightening interview, Dr. Jill Carnahan sits down with the renowned functional medicine practitioner, Dr. Izabella Wentz, to discuss the Adrenal Transformation Protocol. 2019 Nov;17(11):835-841. doi: 10.1016/S1875-5364(19)30101-3. Oral supplementation with Akk after FMT with non-responder feces restores the efficacy of PD-1 blockade in an IL-12-dependent manner by increasing the recruitment of CCR9+CXCR3+CD4+T lymphocytes into mouse tumor beds [151]. Akkermansia muciniphila is an extremely unique probiotic that makes its home in your gut. Lipoteichoic acid from the cell wall of a heat killed Lactobacillus paracasei D3-5 ameliorates aging-related leaky gut, inflammation and improves physical and cognitive functions: From C. elegans to mice. Metab. Administration in IL10/ mice of two commonly used food emulsifiers, carboxymethylcellulose (CMC) or polysorbate-80 (P80), both reduced microbial diversity, but, in particular, promoted the abundance of Akk, colitis, and metabolic syndrome, which may have triggered an excessive immune response, thereby disrupting mucus secretion and causing intestinal barrier damage in the IL10/ mice, demonstrating that Akk is involved in promoting disease progression in some specific situations [189]. Nature 473: 174180. Akkermansia muciniphila is not only a crucial biomarker that indicates the physiology of human beings but also has huge potential to become a probiotic given its physiological benefits in various clinical scenarios. Abiraterone acetate preferentially enriches for the gut commensal Akkermansia muciniphila in castrate-resistant prostate cancer patients. Aged mice administration of Akk (4.9 108 CFU) ameliorates intestinal integrity and homeostasis by inhibiting the infiltration of the proinflammatory molecule LPS, accelerating the renewal and turnover of intestinal cells, and increasing the abundance of Akk in the gut microbiome [137]. In an excess-acetaminophen-induced liver injury mouse model, administration of Akk efficiently alleviated acetaminophen-induced liver injury by attenuating oxidative stress and inflammation in the liver, this hepatoprotective effect accompanied by the activation of the PI3K/Akt pathway and mediated by regulation of the composition and metabolic function of the intestinal microbiota [118]. The genotypes of Akk impact the efficiency of its inhibiting brown adipose tissue whitening and inflammation. Hall K.E., Proctor D.D., Fisher L., Rose S. American gastroenterological association future trends committee report: Effects of aging of the population on gastroenterology practice, education, and research. Review explores crosstalk between cranberries, gut microbiota and microRNAs Up to now, more than 566 papers associated with Akk have been published, with obesity and diabetes as the factors under the greatest focus, and cancer has been the hot topic of recent Akk research [11]. CRC: colorectal cancer; HCC: hepatocellular carcinoma. FMT and co-housing experiments reveal that predisposing gut microbiota is required for the enhanced susceptibility to colitis of TLR4/ mice, and TLR4 knockout suppresses RORt+ Treg cells to exacerbate colitis in a gut-microbiota-dependent manner; additionally, colonic RORt+ Treg cell frequency is negatively correlated with colitis severity [108]. Individuals with obesity have a significantly higher abundance of Firmicutes, whereas the abundance of Akk is significantly decreased in individuals with obesity and diabetes; it is inversely associated with body fat mass and glucose intolerance [45,46,47]. Halmos E.P., Christophersen C.T., Bird A.R., Shepherd S.J., Muir J.G., Gibson P.R. Full article: The role of the probiotic Akkermansia muciniphila in Meaning it doesnt require outside food in order to thrive. National Library of Medicine Comparative effects of alive and pasteurized Akkermansia muciniphila on Vemuri R., Shinde T., Gundamaraju R., Gondalia S.V., Karpe A.V., Beale D.J., Martoni C.J., Eri R. DDS-1 Modulates the Gut Microbiota and Improves Metabolic Profiles in Aging Mice. Pinto, F. C. S., Silva, A. Yep, its a mouthful. In addition, Akk and Amuc_1100 promote intestinal stem cell proliferation mediated by Wnt/-catenin and/or FPR1/NOX1 signaling pathways to accelerate intestinal epithelial renewal and protect the gut barrier. PilQ, a 95-kD protein, is the most abundant outer membrane protein, and is annotated and predicted to be a type IV pili secretin [34]. Shen J., Tong X., Sud N., Khound R., Song Y., Maldonado-Gomez M.X., Walter J., Su Q. Low-Density Lipoprotein Receptor Signaling Mediates the Triglyceride-Lowering Action of Akkermansia muciniphila in Genetic-Induced Hyperlipidemia. Accumulative evidence has shown that the abundance of Akk is decreased in patients with IBD and animal models with colitis, while administration of Akk shows potential anti-inflammatory effects by activating related signaling pathways and immune cells [26,98]. Beneficial metabolic effects of selected probiotics on diet-induced obesity and insulin resistance in mice are associated with improvement of dysbiotic gut microbiota. It is well adapted to the mucous layer, accounting for 1-5% of the fecal microbial . And akkermansia muciniphila is certainly one of the best probiotics for weight loss, restoring gut health, and overall well-being. Furthermore, HFD usually induces chronic liver injury and inflammatory response, whereas supplementation with Akk saves it by regulating lipid metabolism and inhibiting inflammation. The product mentioned in this article are not intended to diagnose, treat, cure, or prevent any disease. Shin and colleagues revealed that the abundance of Akk is significantly increased in co-housing and serum injection mice (from young to aged), whereas it is dramatically reduced in parabiosis mice (where the two mice are connected through the elbow and knee joints, as well as the skin), and the abundance of Amuc_1100 is also significantly increased in co-housing and serum injection mice with the increase in Akk level, which indicates that co-housing and serum injection stimulates Akk growth in the intestine of aged mice [137]. Since Akkermansia probiotics havent gone through enough vigorous testing, these scientists recommend cranberry as a healthy alternative to naturally building Akkermansia in the gut. On one hand, Amuc_1434* can block the G0/G1 phase of the cell cycle of LS174T cells and upregulate tumor protein 53 (p53) expression [35]. Forslund K., Hildebrand F., Nielsen T., Falony G., Le Chatelier E., Sunagawa S., Prifti E., Vieira-Silva S., Gudmundsdottir V., Pedersen H.K., et al. If you are supporting Akkermansia levels through dietary fats and polyphenols, it's much less likely that youll increase Akkermansia too much, unlike supplementing the probiotic directly. Instead of supplements, we recommend using healthy fats to encourage an environment where intestinal mucus is healthy and readily available for this unique probiotic. Fan and colleagues found Akk abundance was significantly reduced in patients with colorectal cancer (CRC) [156]. Typically, higher levels of Akkermansia muciniphila are a good sign. I use BiomeFx because it uses whole genome sequencing to identify the relative presence/non-presence of strains. eCollection 2023. Abe, K., Tsuji, S., Sobue, G., Togo, M. and Itoyama, Y. Please review references sited at end of article for scientific support of any claims made. AS is also an inflammatory disease of the vessel wall, and the major trigger for vessel wall inflammation is hyperlipidemia [86,87]. Brenner D., Hiergeist A., Adis C., Mayer B., Gessner A., Ludolph A.C., Weishaupt J.H. Its difficult to test your own Akkermansia muciniphila levels, but certain symptoms might give you a peek into whether or not your Akkermansia is thriving. Future research will be warranted to know how EVs derived from Akk regulate host metabolism and maintain intestinal homeostasis, as well as evaluate their safe dose and oral administration safety for humans. These nanovesicles can enter and accumulate in bone tissues to attenuate an ovx-induced osteoporotic phenotype by augmenting osteogenic activity and inhibiting osteoclast formation [42]. Infants exposed to higher milk betaine content during breastfeeding show higher fecal Akk abundance, and mouse pups during the lactation period treated with Akk partially replicated the beneficial effects of maternal breast milk betaine, including increased intestinal goblet cell number, lower adiposity, and improved glucose homeostasis during adulthood [190]. Abbreviations: ALD: alcoholic liver disease; ASH: alcoholic steatohepatitis; NAFLD: non-alcoholic fatty liver disease; NASH: non-alcoholic steatohepatitis; HCC: hepatocellular carcinoma; WD: Western diet; HFD: high-fat diet; HFHC: high-fat high-cholesterol; TLRs: Toll-like receptors; LPS: lipopolysaccharide; TG: triglyceride; T-CHO: total cholesterol; AS: atherosclerosis; TMA: trimethylamine; TMAO: trimethylamine-N-oxide; T2D: type 2 diabetes; T1D: type 2 diabetes; NOD: non-obese diabetes; IBD: inflammatory bowel disease; CD: Crohns disease; UC: ulcerative colitis; IBS: irritated bowel syndrome; CD8+ CTLs: CD8+ cytotoxic T lymphocytes; CCl4: carbon tetrachloride; SCFAs: short-chain fatty acids; ERA: enthesitis-related arthritis; K/BxN: KRN/B6xNOD mice; M: macrophages; Tregs: regulatory T cells; DCs: dendritic cells; HDACs: histone deacetylases; TJ: tight junction; MS: metabolic syndromes. Diabetes is a complex metabolic syndrome characterized by insulin dysfunction and glucose and lipid metabolism abnormalities, including type 1 diabetes (T1D) and T2D [57]. Meng X., Zhang J., Wu H., Yu D., Fang X. Aspartic Protease Amuc_1434* Inhibits Human Colorectal Cancer LS174T Cell Viability via TRAIL-Mediated Apoptosis Pathway. (11)(4)(1), Early studies also show that it may be helpful in cancer treatment, alongside traditional cancer therapy, though more research is needed. Akkermansia muciniphila in the Human Gastrointestinal Tract: When, Where, and How?. Derrien M., van Passel M.W., van de Bovenkamp J.H., Schipper R.G., de Vos W.M., Dekker J. Mucin-bacterial interactions in the human oral cavity and digestive tract. The Akkermansia Company to launch pasteurised healthy bacteria Akkermansia is one of the top 20 most common microbial species existing in the human gut microbiome (the community of microorganisms that live in the gut). Moreover, A. muciniphila may have a value in modifying cancer treatment. Sovran B., Hugenholtz F., Elderman M., Van Beek A.A., Graversen K., Huijskes M., Boekschoten M.V., Savelkoul H.F.J., De Vos P., Dekker J., et al. 2019 Nov;12(6):1109-1125. doi: 10.1111/1751-7915.13410. Since your body cant make omega 3s and omega 6s on its own, it needs to pull these nutrients from food. van der Lugt B., van Beek A.A., Aalvink S., Meijer B., Sovran B., Vermeij W.P., Brandt R.M.C., de Vos W.M., Savelkoul H.F.J., Steegenga W.T., et al. Dietary polyphenols such as cranberry extract (CE), black raspberries, pomegranate ellagitannin, epigallocatechin-3-gallate (EGCG), and grape proanthocyanidin significantly ameliorate gut inflammation and related metabolism indicators as well as increases the abundance of Akk in mice [169,176,177,178,179,180,181,182]. Plovier H., Everard A., Druart C., Depommier C., Van Hul M., Geurts L., Chilloux J., Ottman N., Duparc T., Lichtenstein L., et al. The duality and challenge of Akkermansia muciniphila in metabolic syndrome and inflammation therapy. Dao, M. C., Everard, A., Aron-Wisnewsky, J., Sokolovska, N., Prifti, E., Verger, E. O., Kayser, B. D., Levenez, F., Chilloux, J., Hoyles, L., Dumas, M. E., Rizkalla, S. W., Dor, J., Cani, P. D., & Clment, K. (2015). Basolo A., Hohenadel M., Ang Q.Y., Piaggi P., Heinitz S., Walter M., Walter P., Parrington S., Trinidad D.D., von Schwartzenberg R.J., et al. Akkermansia muciniphila as a Next-Generation Probiotic in Modulating Bouma G., Strober W. The immunological and genetic basis of inflammatory bowel disease. For instance, Akk can maintain gut barrier function, reshape the perturbed microbial community, and promote SCFA secretion [41]. (2016). Cross-talk between Akkermansia muciniphila and multiple gut organs alleviates obesity and diabetes. Glucosamine-6-phosphate (GlcN6P) exists in mucin and is also necessary for Akk growth, promoting adaptation to the mucosal niche [23]. and X.Z. Akkermansia muciniphila: a promising target for the therapy of metabolic syndrome and related diseases. For instance, EVs promote TJ expression by activating AMPK and Amuc_1434; upregulate cell cycle, p53 expression, and TRAIL-Caspase-8 pathway to promote apoptosis; and ultimately suppress cancer cell viability. Eradication of Helicobacter typhlonius in young conventional mice using antibiotics decreased the number of intestinal tumors, and the additional presence of Akk prior to antibiotic treatment reduced the tumor number even further [18]. For instance, Akk and Helicobacter typhlonius double colonization significantly reduces the number of intestinal tumors, the mucus layer thickness, and goblet cell density of Fabpl Cre; Apc15lox/+ mice. Li J., Lin S., Vanhoutte P.M., Woo C.W., Xu A. Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe-/- Mice. This site needs JavaScript to work properly. Institute of Feed Science, College of Animal Sciences, Zhejiang University, Key Laboratory of Molecular Animal Nutrition (Zhejiang University), Ministry of Education, Key Laboratory of Animal Feed and Nutrition of Zhejiang Province, Hangzhou 310058, China. Propionate, one of the SCFAs derived from Akk, activates GPR43 of Tregs to promote Tregs differentiation to secret IL-10. government site. A recent study on polyphenols details how cranberry extract triggers a unique response from the intestinal mucus layer. Rhubarb (a Chinese herbal medicine), caloric restriction, and vancomycin treatment also promote the abundance of Akk, whereas HFD and alcohol reduce it [169]. This may imply that Akk can integrate gut microbiota with host brain energy metabolism to ameliorate brain cognitive function mediated by the gutbrain axis. On the other hand, Akk is a strictly anaerobic Gram-negative strain whose growth needs strictly anaerobic environments in vitro. Colonization of Akk ameliorates intestinal mucosal damage associated with inflammation, gut morphological damage, and body weight of chickens caused by S. pullorum infection via accelerating proliferation of intestinal epithelium mediated by the activation of the Wnt/-catenin signaling pathway and the restoration of the damaged intestinal mucosa, increasing the number of goblet cells, and up-regulating the expression of Muc2 and trefoil factor 2 (Tff2) [164].
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