Gut microbiota utilize immunoglobulin A for mucosal colonization

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Abstract

The immune system responds vigorously to microbial infection, while permitting life-long colonization by the microbiome. Mechanisms that facilitate the establishment and stability of the gut microbiota remain poorly described. We discovered that a sensor/regulatory system in the prominent human commensal Bacteroides fragilis modulates its surface architecture to invite binding of immunoglobulin A (IgA). Specific immune recognition facilitated bacterial adherence to cultured intestinal epithelial cells and intimate association with the gut mucosal surface in vivo. The IgA response was required for B. fragilis, and other commensal species, to occupy a defined mucosal niche that mediated stable colonization of the gut through exclusion of exogenous competitors. Therefore, in addition to its role in pathogen clearance, we propose that IgA responses can be co-opted by the microbiome to engender robust host-microbial symbiosis.

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A microbial symbiosis factor prevents intestinal inflammatory disease.

Sarkis Mazmanian, June Round, Dennis Kasper (2008)

Humans are colonized by multitudes of commensal organisms representing members of five of the six kingdoms of life; however, our gastrointestinal tract provides residence to both beneficial and potentially pathogenic microorganisms. Imbalances in the composition of the bacterial microbiota, known as dysbiosis, are postulated to be a major factor in human disorders such as inflammatory bowel disease. We report here that the prominent human symbiont Bacteroides fragilis protects animals from experimental colitis induced by Helicobacter hepaticus, a commensal bacterium with pathogenic potential. This beneficial activity requires a single microbial molecule (polysaccharide A, PSA). In animals harbouring B. fragilis not expressing PSA, H. hepaticus colonization leads to disease and pro-inflammatory cytokine production in colonic tissues. Purified PSA administered to animals is required to suppress pro-inflammatory interleukin-17 production by intestinal immune cells and also inhibits in vitro reactions in cell cultures. Furthermore, PSA protects from inflammatory disease through a functional requirement for interleukin-10-producing CD4+ T cells. These results show that molecules of the bacterial microbiota can mediate the critical balance between health and disease. Harnessing the immunomodulatory capacity of symbiosis factors such as PSA might potentially provide therapeutics for human inflammatory disorders on the basis of entirely novel biological principles.

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Immunoglobulin A coating identifies colitogenic bacteria in inflammatory bowel disease.

Noah W Palm, Marcel de Zoete, Thomas W Cullen … (2014)

Specific members of the intestinal microbiota dramatically affect inflammatory bowel disease (IBD) in mice. In humans, however, identifying bacteria that preferentially affect disease susceptibility and severity remains a major challenge. Here, we used flow-cytometry-based bacterial cell sorting and 16S sequencing to characterize taxa-specific coating of the intestinal microbiota with immunoglobulin A (IgA-SEQ) and show that high IgA coating uniquely identifies colitogenic intestinal bacteria in a mouse model of microbiota-driven colitis. We then used IgA-SEQ and extensive anaerobic culturing of fecal bacteria from IBD patients to create personalized disease-associated gut microbiota culture collections with predefined levels of IgA coating. Using these collections, we found that intestinal bacteria selected on the basis of high coating with IgA conferred dramatic susceptibility to colitis in germ-free mice. Thus, our studies suggest that IgA coating identifies inflammatory commensals that preferentially drive intestinal disease. Targeted elimination of such bacteria may reduce, reverse, or even prevent disease development. Copyright © 2014 Elsevier Inc. All rights reserved.

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Bacterial colonization factors control specificity and stability of the gut microbiota

S Lee, Gregory Donaldson, Zbigniew Mikulski … (2013)

Mammals harbor a complex gut microbiome, comprised of bacteria that confer immunologic, metabolic and neurologic benefits 1 . Despite advances in sequence-based microbial profiling and myriad studies defining microbiome composition during health and disease, little is known about the molecular processes employed by symbiotic bacteria to stably colonize the gastrointestinal (GI) tract. We sought to define how mammals assemble and maintain the Bacteroides, one of the most numerically prominent genera of the human microbiome. While the gut normally contains hundreds of bacterial species 2,3 , we surprisingly find that germ-free mice mono-associated with a single Bacteroides are resistant to colonization by the same, but not different, species. To identify bacterial mechanisms for species-specific saturable colonization, we devised an in vivo genetic screen and discovered a unique class of Polysaccharide Utilization Loci (PUL) that are conserved among intestinal Bacteroides. We named this genetic locus the commensal colonization factors (ccf). Deletion of the ccf genes in the model symbiont, Bacteroides fragilis, results in colonization defects in mice and reduced horizontal transmission. The ccf genes of B. fragilis are up-regulated during gut colonization, preferentially at the colonic surface. When we visualize microbial biogeography within the colon, B. fragilis penetrates the colonic mucus and resides deep within crypt channels, while ccf mutants are defective in crypt association. Remarkably, the CCF system is required for B. fragilis colonization following microbiome disruption with Citrobacter rodentium infection or antibiotic treatment, suggesting the niche within colonic crypts represents a reservoir for bacteria to maintain long-term colonization. These findings reveal that intestinal Bacteroides have evolved species-specific physical interactions with the host that mediate stable and resilient gut colonization, and the CCF system represents a novel molecular mechanism for symbiosis.

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Journal

Title: Science

Abbreviated Title: Science

Publisher: American Association for the Advancement of Science (AAAS)

ISSN (Print): 0036-8075

ISSN (Electronic): 1095-9203

Publication date Created: May 17 2018

Publication date Created: May 18 2018

Publication date (Print): May 18 2018

Publication date (Electronic): May 03 2018

Volume: 360

Issue: 6390

Pages: 795-800

Article

DOI: 10.1126/science.aaq0926

PMC ID: 5973787

PubMed ID: 29724905

SO-VID: 5780fb9d-0fcc-4c44-b84b-e0c2880dcea1

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Gut microbiota utilize immunoglobulin A for mucosal colonization

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Most cited references 35

A microbial symbiosis factor prevents intestinal inflammatory disease.

Immunoglobulin A coating identifies colitogenic bacteria in inflammatory bowel disease.

Bacterial colonization factors control specificity and stability of the gut microbiota

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Cited by 238

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