Biogeography of the Relationship between the Child Gut Microbiome and Innate Immune System.

Autor:	Amenyogbe N; Department of Experimental Medicine, University of British Columbia, Vancouver, Canada.; Telethon Kids Institute, Perth, Australia., Dimitriu P; Department of Microbiology and Immunology, Life Sciences Institute, University of British Columbia, Vancouver, Canada., Smolen KK; Department of Experimental Medicine, University of British Columbia, Vancouver, Canada., Brown EM; Michael Smith Laboratories, University of British Columbia, Vancouver, Canada., Shannon CP; PROOF Centre of Excellence, St. Pauls's Hospital, University of British Columbia, Vancouver, Canada., Tebbutt SJ; PROOF Centre of Excellence, St. Pauls's Hospital, University of British Columbia, Vancouver, Canada.; Centre for Lung Innovation, Department of Medicine, Division of Respiratory Medicine, University of British Columbia, Vancouver, Canada., Cooper PJ; Facultad de Ciencias Medicas, de la Salud y la Vida, Universidad Internacional del Ecuador, Quito, Ecuador.; Institute of Infection and Immunity, St. George's University of London, London, United Kingdom., Marchant A; Institut d'Immunologie Médicale, Université Libre de Bruxelles, Charleroi, Belgium., Goetghebuer T; Département de Pédiatrie, Centre Hospitalier Universitaire St Pierre, Université Libre de Bruxelles, Brussels, Belgium., Esser M; Immunology Unit, Division of Medical Microbiology, Department of Pathology, NHLS and Stellenbosch University, Matieland, Stellenbosch, South Africa., Finlay BB; Michael Smith Laboratories, University of British Columbia, Vancouver, Canada., Kollmann TR; Department of Pediatrics, Division of Infectious Diseases, University of British Columbia, Vancouver, Canada.; Telethon Kids Institute, Perth, Australia., Mohn WW; Department of Microbiology and Immunology, Life Sciences Institute, University of British Columbia, Vancouver, Canada wmohn@mail.ubc.ca.
Jazyk:	angličtina
Zdroj:	MBio [mBio] 2021 Jan 12; Vol. 12 (1). Date of Electronic Publication: 2021 Jan 12.
DOI:	10.1128/mBio.03079-20
Abstrakt:	The gut microbiome is a well-recognized modulator of host immunity, and its compositions differ between geographically separated human populations. Systemic innate immune responses to microbial derivatives also differ between geographically distinct human populations. However, the potential role of the microbiome in mediating geographically varied immune responses is unexplored. We here applied 16S amplicon sequencing to profile the stool microbiome and, in parallel, measured whole-blood innate immune cytokine responses to several pattern recognition receptor (PRR) agonists among 2-year-old children across biogeographically diverse settings. Microbiomes differed mainly between high- and low-resource environments and were not strongly associated with other demographic factors. We found strong correlations between responses to Toll-like receptor 2 (TLR2) and relative abundances of Bacteroides and Prevotella populations, shared among Canadian and Ecuadorean children. Additional correlations between responses to TLR2 and bacterial populations were specific to individual geographic cohorts. As a proof of concept, we gavaged germfree mice with human donor stools and found murine splenocyte responses to TLR stimulation were consistent with responses of the corresponding human donor populations. This study identified differences in immune responses correlating to gut microbiomes across biogeographically diverse settings and evaluated biological plausibility using a mouse model. This insight paves the way to guide optimization of population-specific interventions aimed to improve child health outcomes. IMPORTANCE Both the gut microbiome and innate immunity are known to differ across biogeographically diverse human populations. The gut microbiome has been shown to directly influence systemic immunity in animal models. With this, modulation of the gut microbiome represents an attractive avenue to improve child health outcomes associated with altered immunity using population-specific approaches. However, there are very scarce data available to determine which members of the gut microbiome are associated with specific immune responses and how these differ around the world, creating a substantial barrier to rationally designing such interventions. This study addressed this knowledge gap by identifying relationships between distinct bacterial taxa and cytokine responses to specific microbial agonists across highly diverse settings. Furthermore, we provide evidence that immunomodulatory effects of region-specific stool microbiomes can be partially recapitulated in germfree mice. This is an important contribution toward improving global child health by targeting the gut microbiome. (Copyright © 2021 Amenyogbe et al.)
Databáze:	MEDLINE
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