The Compromised Mucosal Immune System of β7 Integrin-Deficient Mice Has Only Minor Effects on the Fecal Microbiota in Homeostasis

Abstract

The gastrointestinal tract is an ideal habitat for diverse bacterial species that reside in a homeostatic balance with local tissue and significantly contribute to host health. Negative shifts in gut microbiota profiles, also known as dysbiosis, may be implicated in the development of chronic disorders such as inflammatory bowel diseases (IBD). Adhesion molecule-dependent recruitment of immune cells to the gut is an important step in IBD pathogenesis. The adhesion molecule β7 integrin contributes to the development of the gut-associated lymphoid tissue (GALT), intestinal immune cell homing, and immune responses and is known to promote intestinal inflammation. Although many studies underlined the role of the gut microbiota in shaping the mucosal immune system, studies on the influence of the host immune system on the microbiota are rare, especially in homeostasis. We addressed this question via comparative 16S rRNA gene amplicon analysis of fecal microbial communities from wild-type and β7 integrin-deficient mice, the latter being characterized by a compromised GALT. Besides subtle changes in relative abundances of Muribaculaceae spp. and unknown members of the families Ruminococcaceae and Lachnospiraceae, there was altogether no major difference in microbiota profiles in β7 integrin-deficient mice vs. wild-type littermates. This indicates that, in conditions of homeostasis, there is only a minor influence of the host immune system on the fecal microbiota in our mouse model, stressing the potential importance of pathological factors for dysbiosis development.

Ascorbic Acid Derivative 2-O-β-d-Glucopyranosyl-l-Ascorbic Acid from the Fruit of Lycium barbarum Modulates Microbiota in the Small Intestine and Colon and Exerts an Immunomodulatory Effect on Cyclophosphamide-Treated BALB/c Mice

“…Muribaculaceae is a freshly renamed family, which is formerly named as S24-7 . It has been reported that Muribaculaceae is positively correlated with immune response including natural killer cell and NF-κB signaling, and the family members of Muribaculaceae can interact with both innate and adaptive immune responses via IgA coating . Rikenellaceae, reported to present a higher relative abundance in ovalbumin/staphylococcal enterotoxin B-sensitized mice, was found to be reduced by AA-2βG in our present study.…”

“…57 It has been reported that Muribaculaceae is positively correlated with immune response including natural killer cell and NF-κB signaling, 58 and the family members of Muribaculaceae can interact with both innate and adaptive immune responses via IgA coating. 59 Rikenellaceae, reported to present a higher relative abundance in ovalbumin/ staphylococcal enterotoxin B-sensitized mice, 60 was found to be reduced by AA-2βG in our present study. Similarly, the relative abundance of Rikenellaceae in both IBD mouse models and long-term intervened normal mouse models was reduced by AA-2βG.…”

Antibody secreting cells are critically dependent on integrin α4β7/MAdCAM-1 for intestinal recruitment and control of the microbiota during chronic colitis

“…A similar expansion of Clostridia species was also detected in our study and recapitulated in IgA-deficient IL-10 −/− mice. Recently, minimal distortion of the resident microbiota composition was found in β7 −/− mice under homeostatic conditions, despite significant perturbation of the intestinal B-cell compartment 33 . However, it is possible that a baseline dysregulation of the microflora that is known to occur in inflamed IL-10 −/− mice 34 is required for the accentuated effect of β7/IgA deficiency to take place.…”

An integrin αEβ7-dependent mechanism of IgA transcytosis requires direct plasma cell contact with intestinal epithelium

“… 21 , 22 PIgR transcripts were clearly increased, suggesting that the epithelium senses the intraluminal IgA deficit, likely though TLR engagement of pathogen-associated molecular patterns, originating from an altered microbiota composition. 38 In the ileal LP, we found 3 main B cell subsets, based on their expression of CD19 (shed upon class switching) and surface IgA. The CD19 + cells appeared to be in their earliest state of maturation as they had the highest nucleocytoplasmic ratio, expressed IgM, IgD, CCR7, and S1PR1.…”