@article{456fc1dfc5c34f2d99926b1d59e8b699,
title = "Akkermansia muciniphila and Parabacteroides distasonis synergistically protect from colitis by promoting ILC3 in the gut",
abstract = "Inflammatorybowel disease (IBD) is a group of inflammatoryconditions of the gastrointestinal tract. The etiology of IBD remains elusive, but the disease is suggested to arise from the interaction of environmental and genetic factors that trigger inadequate immune responses and inflammationin the intestine. The gut microbiome majorly contributes to disease as an environmental variable, and although some causative bacteria are identified,little is known about which specificmembers of the microbiome aid in the intestinal epithelial barrier function to protect from disease. While chemically inducing colitis in mice from two distinct animal facilities, we serendipitously found that mice in one facility showed remarkable resistance to disease development, which was associated with increased markers of epithelial barrier integrity. Importantly, we show that Akkermansia muciniphila and Parabacteroides distasonis were significantlyincreased in the microbiota of resistant mice. To causally connect these microbes to protection against disease, we colonized susceptible mice with the two bacterial species. Our results demonstrate that A. muciniphila and P. distasonis synergistically drive a protective effectin both acute and chronic models of colitis by boosting the frequency of type 3 innate lymphoid cells in the colon and by improving gut epithelial integrity. Altogether, our work reveals a combined effortof commensal microbes in offeringprotection against severe intestinal inflammationby shaping gut immunity and by enhancing intestinal epithelial barrier stability. Our study highlights the beneficialrole of gut bacteria in dictating intestinal homeostasis, which is an important step toward employing microbiome-driven therapeutic approaches for IBD clinical management.",
keywords = "Akkermansia muciniphila, colitis, gut immunity, ILC, microbiome, Parabacteroides distasonis",
author = "Joana Gaifem and Ana Mendes-Frias and Mathis Wolter and Alex Steimle and Garz{\'o}n, {Maria Jose} and Carles Ubeda and Clarisse Nobre and Abigail Gonz{\'a}lez and Pinho, {Salom{\'e} S.} and Cristina Cunha and Agostinho Carvalho and Castro, {Ant{\'o}nio Gil} and Desai, {Mahesh S.} and Fernando Rodrigues and Ricardo Silvestre",
note = "ACKNOWLEDGMENTS We thank Eric Martens and Nicholas Pudlo at University of Michigan for providing the mouse Akkermansia muciniphila strain. This work was funded by national funds, through the Foundation for Science and Technology (project UIDB/50026/2020, UIDP/50026/2020, and UIDB/04469/2020; contracts DOI 10.54499/2020.00185.CEECIND/CP1600/CT0004 to R.S.; PD/BD/106053/2015 via InterUniversity Doctoral Programme in Ageing and Chronic Disease, PhDOC and DOI 10.54499/2020.00088.CEECIND/CP1608/CT0001 to J.G.; 10.54499/CEECIND/04058/2018/CP1581/CT0015 to C.C., 2021.07836.BD to A.F.; 2021.06268.BD to A.G.; and DOI 10.54499/2021.01234.CEECIND/CP1664/CT0019 to C.N., as well as by Associate Laboratory in Biotechnology, Bioengineering, and Microelectromechanical Systems, LA/P/0029/2020. J.G. also acknowledges the European Society of Clinical Microbiology and Infectious Diseases (research grant 2022) and European Crohn{\textquoteright}s and Colitis Organisation (ECCO grant 2023) for funding. S.S.P. acknowledges funding from ECCO Pioneer Award 2022. This work was also supported by the following grants: in the laboratory of M.S.D.: Luxembourg National Research Fund (FNR) CORE (C15/BM/10318186 and C18/BM/12585940) grants and FNR BRIDGES grant (22/17426243) and PID2020-120292RB-I00 from MICINN and CIPROM/2021/053 from Conselleria d{\textquoteright}Innovaci{\'o}, Universitats, Ci{\`e}ncia i Societat Digital to C.U. Publisher Copyright: {\textcopyright} 2024 Gaifem et al.",
year = "2024",
month = apr,
day = "10",
doi = "10.1128/mbio.00078-24",
language = "English",
volume = "15",
journal = "mBio",
issn = "2161-2129",
publisher = "American Society for Microbiology",
number = "4",
}