The systemic anti-microbiota IgG repertoire can identify gut bacteria that translocate across gut barrier surfaces

Abstract

Unique gut microbiota compositions have been associated with inflammatory diseases, but identifying gut bacterial functions linked to immune activation in humans remains challenging. Translocation of pathogens from mucosal surfaces into peripheral tissues can elicit immune activation, although whether and which gut commensal bacteria translocate in inflammatory diseases is difficult to assess. We report that a subset of commensal gut microbiota constituents that translocate across the gut barrier in mice and humans are associated with heightened systemic immunoglobulin G (IgG) responses. We present a modified high-throughput, culture-independent approach to quantify systemic IgG against gut commensal bacteria in human serum samples without the need for paired stool samples. Using this approach, we highlight several commensal bacterial species that elicit elevated IgG responses in patients with inflammatory bowel disease (IBD) including taxa within the clades Collinsella , Bifidobacterium , Lachnospiraceae , and Ruminococcaceae . These and other taxa identified as translocating bacteria or targets of systemic immunity in IBD concomitantly exhibited heightened transcriptional activity and growth rates in IBD patient gut microbiomes. Our approach represents a complementary tool to illuminate interactions between the host and its gut microbiota and may provide an additional method to identify microbes linked to inflammatory disease.

TheEscherichia coliTolC efflux pump protein is immunogenic and elicits protective antibodies

“…Non-immunized mice also presented anti-TolC IgM and IgG antibodies, when serum was diluted at 1:40, which was not seen in Germ-free mice. These findings suggest that mice microbiota could have a role in TolC elicited antibodies, probably due to the E. coli translocation ability 41,42 . The presence of anti-TolC IgM, IgG and IgA in healthy human subjects corroborates this hypothesis.…”

MNNMDA: Predicting human microbe-disease association via a method to minimize matrix nuclear norm

“…Clostridium coccoides are less represented in A-IBD patients [67] . Lachnospiraceae and other taxa identified as translocating bacteria or targets of systemic immunity in IBD concomitantly exhibited heightened transcriptional activity and growth rates in IBD patient gut microbiomes [68] . The changes in the abundance of Proteobacteria of IBD patients are not only related to current activity but also to the course of the disease [69] .…”

Longitudinal gut microbiome analyses and blooms of pathogenic strains during lupus disease flares

“…Neonatal colonisation with the S107-48 strain led to RG translocation into draining mesenteric lymph nodes, and induction of serum IgG anti-DNA antibodies at levels proportional to the induced functional impairment of the gut barrier 33. This may be a fundamental principle, as more recently serum IgG-antibodies in IBD and rheumatoid arthritis patients have been shown to recognise gut commensals, presumably based on similar mechanisms 38 39…”