A Potential Role for Stress-Induced Microbial Alterations in IgA-Associated Irritable Bowel Syndrome with Diarrhea

Abstract

Highlights d Stress in mice causes diarrhea, dysbiosis, barrier defect, increased antibacterial IgA d Stress-induced microbial changes are sufficient to elicit the above effects d IBS-D patients from two cohorts display increased and unique antibacterial IgA d Antibacterial IgA in IBS-D correlates with patient symptom severity

Intestinal Homeostasis under Stress Siege

“…Stress-induced dysbiosis in mice has been associated with gut barrier weakness. These findings mimicked the dysbiosis and IgA-coated microbiota increase found in patients diagnosed with IBS who had diarrhea [ 41 , 59 ].…”

“…Stress feeds a vicious circle between IgA and microbiota disturbances that result in intestinal dysbiosis; that is, disruption of growth and stabilization of microbiota that normally colonize the gut lumen. These changes lead to overgrowth of a predominant microbe communities and the loss of diversity [ 55 , 56 , 57 , 59 , 61 ]. In a murine model of subchronic and mild social defeat stress for 10 days, as a model of depression, stress-induced dysbiosis caused significant (up or down) changes in the abundance of fecal microbiota members; these changes correlated with reduced cecal IgA production [ 56 ].…”

“…In a murine model of subchronic and mild social defeat stress for 10 days, as a model of depression, stress-induced dysbiosis caused significant (up or down) changes in the abundance of fecal microbiota members; these changes correlated with reduced cecal IgA production [ 56 ]. Stress-associated dysbiosis might lead to both elicitation of luminal IgA or IgA-coated microbiota that reflect outgoing inflammatory perturbations [ 55 , 57 , 59 , 61 ]. In this regard, in mice subjected to chronic WAS for 1 h a day for 8 days, stress in combination with antibiotics exacerbated the dysbiosis, and there were more wall-adhered microbiota and increased cecal SIgA production [ 55 ].…”

“…Opening goblet cell gaps is inhibited by microbiota-induced Myd88 (a TLR signal protein adapter) activation by blunting the goblet cell response to acetylcholine [ 75 ]. Moreover, stress-induced gaps lead to diarrhea, increased bacterial translocation related to an enhanced IgA microbiota response, and more IgA-coated microbiota [ 59 ]. Stress-induced dysbiosis in mice has been associated with gut barrier weakness.…”

“…In neonatal rats subjected to 3 h of maternal separation during 35 postnatal days hyperpermeability, dysbiosis, and a decreased mucin layer in all intestinal regions were observed [ 58 ]. In SPF C57BL/6 mice subjected to restraint stress for 2 h a day for 7 days, dysbiosis and the IgA-bound fecal level were increased along with increased opening colonic goblet cell gaps in response to acetylcholine [ 59 , 75 ]. There was increased opening of goblet cell gaps, decreased IgA, and increased Escherichia coli translocation to mesenteric lymph nodes in rats exposed to heat stress [ 48 ].…”