Intestinal IgA Regulates Expression of a Fructan Polysaccharide Utilization Locus in Colonizing Gut Commensal Bacteroides thetaiotaomicron

Abstract

Given the significant impact that gut microbes have on our health, it is essential to identify key host and environmental factors that shape this diverse community. While many studies have highlighted the impact of diet on gut microbiota, little is known about how the host regulates this critical diet-microbiota interaction. In our present study, we discovered that gut IgA targeted a protein complex involved in the utilization of an important dietary polysaccharide: fructan. While the presence of dietary fructans was previously thought to allow unrestricted growth of fructan-utilizing bacteria, our work shows that gut IgA, by targeting proteins responsible for fructan utilization, provides the host with tools that can restrict the microbial utilization of such polysaccharides, thereby controlling their growth.

The Immunomodulatory Properties of β-2,6 Fructans: A Comprehensive Review

“…L. mesenteroides NTM048 levansucrase-synthesised levan and L. mesenteroides NTM048 EPS but not B. subtilis levan were shown to induce IgA production in isolated murine peyer’s patches [ 109 ]. These differences may be due to the capacity of IgA to target different microbial antigens [ 123 ]. For example, IgA was proposed to target proteins associated with the B. thetaiotaomicron fructan-associated PS utilization locus [ 123 ].…”

“…These differences may be due to the capacity of IgA to target different microbial antigens [ 123 ]. For example, IgA was proposed to target proteins associated with the B. thetaiotaomicron fructan-associated PS utilization locus [ 123 ]. Therefore, this mechanism may play an indirect role in gut colonisation and host-microbial mutualism [ 123 ].…”

“…For example, IgA was proposed to target proteins associated with the B. thetaiotaomicron fructan-associated PS utilization locus [ 123 ]. Therefore, this mechanism may play an indirect role in gut colonisation and host-microbial mutualism [ 123 ]. However, further work is needed to assess the role of microbial levan (or its derivative DFA-IV) from different sources on IgA induction, and whether this can be used as a route to modulate beneficial members of the gut microbiota.…”

Acceptive Immunity: The Role of Fucosylated Glycans in Human Host–Microbiome Interactions

“…In TI pathways, polyreactive, low-affinity IgA2s are produced, which have wide reactivity to diverse, but nevertheless, specific subgroups of microbiota [ 224 ], most likely due to the specificity of bacterial adhesins to IgA glycans and the understudied glycan–glycan interactions [ 225 ]. This non-canonical binding of IgA2 to symbiotic bacteria contributes to the maintenance of colonic resistance of bacteria in the intestine [ 223 , 226 , 227 ]. sIgA of both subclasses have different tissue distribution: Peyer’s patches contain more IgA1 + B cells than lamina propria, and the colon contains mainly IgA2 + B cells [ 227 , 228 ].…”

“…Increased expression of membrane and secreted proteins of B. thetaiotaomicron , involved in the utilization of fructan or pectin from food, leads to the production of sIgA specific to them and suppression of the locus of fructan utilization. This is considered a regulatory mechanism of microbial colonization through their metabolism modulation by the host, as on the one hand it helps to maintain the diversity of the intestinal microbiota in the event of dietary restrictions and changes in food, and on the other hand, it helps to reduce intestinal pro-inflammatory signaling [ 226 ]. B. thetaiotaomicron proteins BT2268 and BT2269 belong to the family of mucus-associated functional factor (MAFF); they contribute not only to colonization by Bacteroides , but also by Firmicutes.…”