Functional characterization of IgA-targeted bacterial taxa from undernourished Malawian children that produce diet-dependent enteropathy

Abstract

To gain insights into the interrelationships among childhood undernutrition, the gut microbiota, and gut mucosal immune/barrier function, we purified bacterial strains targeted by IgA from the fecal microbiota of two cohorts of Malawian infants and children. IgA responses to several bacterial taxa, including Enterobacteriaceae, correlated with anthropometric measurements of nutritional status in longitudinal studies. The relationship between IgA responses and growth was further explained by enteropathogen burden. Gnotobiotic mouse recipients of an IgA+-bacterial consortium purified from the gut microbiota of undernourished children exhibited a diet-dependent enteropathy characterized by rapid disruption of the small intestinal and colonic epithelial barrier, weight loss and sepsis that could be prevented by administering two IgA-targeted bacterial species from a healthy microbiota. Dissection of a culture collection of 11 IgA-targeted strains from an undernourished donor, sufficient to transmit these phenotypes, disclosed that Enterobacteriaceae interacted with other consortium members to produce enteropathy. These findings indicate that bacterial targets of IgA responses have etiologic, diagnostic, and therapeutic implications for childhood undernutrition.

Do the Microbiota Influence Vaccines and Protective Immunity to Pathogens?

“…However, the IgA þ fraction of bacteria from healthy donors did not have such propensity. Similarly, the IgA þ microbiota from undernourished children was enriched for IgA-coated species ( particularly Enterobacteriaceae) that were colitogenic in gnotobiotic mice, but the IgA þ fraction from healthy control donors was largely protective (Kau et al 2015). These results are consistent with the notion that gut bacteria can elicit diverse immune responses, and indicate that their ability to induce bacteria-specific IgA does not need to reflect either pro-and anti-inflammatory barrier immune responses.…”

IL-33 regulates the IgA-microbiota axis to restrain IL-1α–dependent colitis and tumorigenesis

“…Intestinal IgA is one such immune component that preferentially targets colitogenic members of the microbiota, including SFB and A. muciniphila (34,39,41,56,57). Reciprocally, certain pathobionts can produce proteolytic enzymes that degrade intestinal IgA and thereby enhance colitis susceptibility (40).…”

“…We and others have shown that gut microbial dysbiosis contributes to susceptibility toward colitis and CAC (36)(37)(38). IgA is known to regulate the gut microbial landscape, and mice deficient in IgA and pIgR are known to harbor a dysbiotic microbiota that contributes to their increased susceptibility to colitis (33,(39)(40)(41). We therefore posited that decreased colonic IgA in Il33 -/-mice would lead them to developing a dysbiotic microbiota.…”

“…Relative to WT mice, Il33 -/-mice harbored increased levels of Akkermansia muciniphila and segmented filamentous bacteria (SFB), while the levels of bacteria belonging to other class and phyla were similar ( Figure 6, A and B). A. muciniphila is an anaerobic bacterium that specializes in degrading the mucus (42) and is highly targeted by intestinal IgA in healthy individuals (39,41). Recent reports have shown that exogenous Akkermansia administration leads to increased permeability of the mucus barrier and epithelial injury in mice after challenge with noxious agents (43,44).…”

Glyphosate, pathways to modern diseases IV: cancer and related pathologies

“…The authors did not consider possible effects of glyphosate contamination, even though another study has shown significant glyphosate residues in GM soy as compared to conventional soy treated with glyphosate [154]. Pancreatic atrophy of the acinar cells along with degranulation and intracellular fibrillation is a fundamental aspect of the childhood wasting disease kwashiorkor [168], which is linked to disrupted gut microbes [169], and may also be in part attributable to glyphosate poisoning.…”