Gut bacteria Akkermansia is associated with reduced risk of obesity: evidence from the American Gut Project
Tóm tắt
Gut bacteria Akkermansia has been shown an anti-obesity protective effect in previous studies and may be used as promising probiotics. However, the above effect may be confounded by common factors, such as sex, age and diets, which should be verified in a generalized population. We used datasets from the American Gut Project to strictly reassess the association and further examined the effect of aging on it. A total of 10,534 participants aged 20 to 99 years from the United States and the United Kingdom were included. The relative abundance of Akkermansia was assessed based on 16S rRNA sequencing data. Obesity (body mass index, BMI ≥ 30 kg/m2) risks were compared across Akkermansia quintiles in logistic models with adjustment for common confounders. Restricted cubic splines were used to examine dose response effects between Akkermansia, obesity and age. A sliding-windows-based algorithm was used to investigate the effect of aging on Akkermansia-obesity associations.
The median abundance of Akkermansia was 0.08% (interquartile range: 0.006–0.93%), and the prevalence of obesity was 11.03%. Nonlinear association was detected between Akkermansia and obesity risk (P = 0.01). The odds ratios (95% confidence interval) for obesity across the increasing Akkermansia quintiles (referencing to the first quintile) were 1.14 (0.94–1.39), 0.94 (0.77–1.15), 0.70 (0.56–0.85) and 0.79 (0.64–0.96) after adjusting for age and sex (P for trend < 0.001). This association remained unchanged after further controlling for smoking, alcohol drinking, diet, and country. The odds ratios (95% CI) of Akkermansia were 0.19 (0.03–0.62) and 0.77 (0.64–0.91) before and over 40 years, respectively, indicating that the protective effect of Akkermansia against obesity was not stable with aging. High relative abundance of Akkermansia is associated with low risk of obesity and the association declines with aging.
Tài liệu tham khảo
Zhao L. The gut microbiota and obesity: from correlation to causality. Nat Rev Microbiol. 2013;11(9):639.
Gérard and Philippe. Gut microbiota and obesity. Cell. Mol. Life Sci. 2016; 73(1):147–62.
Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006;444(7122):1027–131.
Cani PD, de Vos WM. Next-generation beneficial microbes: the case of Akkermansia muciniphila. Front Microbiol. 2017;8:1765.
Zhang T, Li Q, Cheng L, Buch H, Zhang F. Akkermansia muciniphila is a promising probiotic. Microb Biotechnol. 2019;12:1109–25.
Everard A, Belzer C, Geurts L, Ouwerkerk JP, Druart C, Bindels LB, Guiot Y, Derrien M, Muccioli GG, Delzenne NM. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc Natl Acad Sci USA. 2013;110:9066–71.
Depommier C, Everard A, Druart C, Plovier H, Hul MV, Vieira-Silva S. Falony G, Raes J, Maiter D, Delzenne NM et al. Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study. Nat. Med. 2019; 25(7):1096.
Plovier H, Everard A, Druart C, Depommier C, Van Hul M, Geurts L, Chilloux J, Ottman N, Duparc T, Lichtenstein L, et al. A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice. Nat Med. 2017;23(1):107–13.
Jura M, Kozak LP. Obesity and related consequences to ageing. Age. 2016;38(1):23.
Santacruz A, Collado MC, García-Valdés L, Segura MT, Sanz Y. Gut microbiota composition is associated with body weight, weight gain and biochemical parameters in pregnant women. Br J Nutr. 2010;104(1):83–92.
Escobar JS, Klotz B, Valdes BE, Agudelo GM. The gut microbiota of Colombians differs from that of Americans, Europeans and Asians. BMC Microbiol. 2014;14(1):311.
Derrien M, Belzer C, de Vos WM. Akkermansia muciniphila and its role in regulating host functions. Microbiol Pathog. 2017;9:171–81.
de la Cuesta-Zuluaga J, Kelley ST, Chen Y, Escobar JS, Mueller NT, Ley RE, McDonald D, Huang S, Swafford AD, Knight R, Thackray VG. Age- and sex-dependent patterns of gut microbial diversity in human adults. mSystems 2019: 4(4):e00261–19.
Geerlings S, Kostopoulos I, De Vos W, Belzer C. Akkermansia muciniphila in the human gastrointestinal tract: when, where, and how? Microorganisms. 2018;6(3):75.
McDonald D, Hyde E, Debelius J.W et al. American gut: an open platform for citizen science microbiome research. mSystems 2018; 3(3):e00031-00018.
World Health Organization: Global Database on Body Mass Index (BMI). https://www.who.int/nu-trition/databases/bmi/en/ (30 March 2020, date last accessed).
Rognes T, Flouri T, Nichols B, Quince C, Mahé F. VSEARCH: a versatile open source tool for metagenomics. PeerJ. 2016;4:e2584–e2584.
Quast C, Pruesse E, Yilmaz P, Gerken J, Schweer T, Yarza P, Peplies J, Glockner FO. The SILVA ribosomal RNA gene database project: improved data processing and web-based tools. Nucleic Acids Res. 2013;4(10):D590-596.
Lehallier B, Gate D, Schaum N, et al. Undulating changes in human plasma proteome profiles across the lifespan. Nat Med. 2019;25:1843–50.
Biagi E, Candela M, Turroni S, Garagnani P, Franceschi C, Brigidi P. Ageing and gut microbes: perspectives for health maintenance and longevity. Pharmacol Res. 2013;69(1):11–20.
Deschasaux M, Bouter KE, Prodan A, Levin E, Groen AK, Herrema H, Tremaroli V, Bakker GJ, Attaye I, Pinto-Sietsma SJ, et al. Depicting the composition of gut microbiota in a population with varied ethnic origins but shared geography. Nat Med. 2018;24:1526–31.
Ghosh TS, Das M, Jeffery IB, O'Toole PW. Adjusting for age improves identification of gut microbiome alterations in multiple diseases. eLife 2020; 9:e50240.
Collado MC, Derrien M, Isolauri E, de Vos WM, Salminen S. Intestinal Integrity and Akkermansia muciniphila, a Mucin-Degrading Member of the Intestinal Microbiota Present in Infants, Adults, and the Elderly. Appl Environ Microbiol. 2007;73(23):7767.
Shin NR, Lee JC, Lee HY, Kim MS, Whon TW, Lee MS, Bae JW. An increase in the Akkermansia spp. population induced by metformin treatment improves glucose homeostasis in diet-induced obese mice. Gut. 2014;63(5):727–35.
Dubourg G, Lagier JC, Armougom F, Robert C, Audoly G, Papazian L, Raoult D. High-level colonisation of the human gut by Verrucomicrobia following broad-spectrum antibiotic treatment. Int J Antimicrob Agents. 2013;41(2):149–55.
Guo X, Zhang J, Wu F, Zhang M, Yi M, Peng Y. Different sub-type strains of Akkermansia muciniphila abundantly colonize in southern China. J Appl Microbiol. 2016;120:452–9.
Shin NE, Lee JC, Lee HY, et al. An increase in the Akkermansia spp. population induced by metformin treatment improves glucose homeostasis in diet-induced obese mice. Gut. 2014;63(5):727–35.
Junjie Q, Yingrui L, Zhiming C, Shenghui L, Jianfeng Z, Fan Z, Suisha L, Wenwei Z, Yuanlin G, Dongqian S. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature. 2012;490(7418):55–60.