Immunization with cytolethal distending toxin B produces autoantibodies to vinculin and small bowel bacterial changes in a rat model of postinfectious irritable bowel syndrome

Abstract

Background Recent data substantiate the importance of acute gastroenteritis in the development of irritable bowel syndrome (IBS). An animal model of postinfectious IBS determined the importance of cytolethal distending toxin B (CdtB) during live Campylobacter jejuni infection and its development of autoimmunity to vinculin. In this study, we examine whether subcutaneous exposure to CdtB alone is sufficient to produce the postinfectious IBS effect and autoimmunity. Methods Sixty adult Sprague Dawley rats were randomized into 2 groups to receive subcutaneous injection of either CdtB or vehicle and administered a booster injection of the same product 3 weeks later. Serum was collected for anti‐CdtB and anti‐vinculin titers. Duodenal and ileal luminal contents for total eubacterial qPCR, and ileal bowel segments were harvested for vinculin and ileal expression. In a second experiment, 4 adult, Sprague Dawley rats were injected with either Cy7‐labeled anti‐CdtB and anti‐vinculin antibodies were injected into the tail vein and imaged to determine organ localization of the antibodies. Key Results Rats that received CdtB increased in serum anti‐CdtB after injection. CdtB exposure also precipitated significant elevation in anti‐vinculin antibodies (P < .001). This was associated with a reduction in intestinal vinculin expression (P < .001) that negatively correlated with serum anti‐CdtB levels. CdtB exposure was also associated with greater levels of duodenal (P < .001) and ileal (P < .01) bacteria by qPCR that positively correlated with anti‐CdtB levels. Conclusions and Inferences Rats injected with CdtB developed a postinfectious IBS‐like phenotype and autoimmunity to vinculin with corresponding reduction in intestinal vinculin expression.

Small Intestine Bacterial Overgrowth in Bangladeshi Infants Is Associated With Growth Stunting in a Longitudinal Cohort

“…However, children in the studied population carry a mean of 3.3 enteric pathogens in nondiarrheal stool samples which means pathogens may have acted as confounders to each other in our analysis ( 34 ). It may also be that the 3-month window we investigated for presence or absence of pathogens was insufficient, especially if bacterial overgrowth is due to an autoimmune interaction with the enteric nervous system governing motility in response to a particular infection as suggested by murine models ( 35 , 36 ). However, the associations noted deserve further investigation and validation.…”

The human translation of the postinfectious irritable bowel syndrome like rat model with antivinculin production after immunization with cytolethal distending toxin B

“…We read with interest the paper by Morales et al, reporting an increase in serum anti-CdtB and precipitation of antivinculin antibodies (p < 0.001) after subcutaneous injection of CdtB in a rat model. 1 This was associated with a reduction in intestinal vinculin expression (p < 0.001) negatively correlated with serum anti-CdtB levels. They concluded that rats injected with CdtB developed a postinfectious (PI) irritable bowel syndrome (IBS)-like phenotype, and an autoimmune reduction in intestinal vinculin expression.…”

“…They concluded that rats injected with CdtB developed a postinfectious (PI) irritable bowel syndrome (IBS)-like phenotype, and an autoimmune reduction in intestinal vinculin expression. 1 To translate these results into humans, we retrospectively examined data of 33 patients that were studied for chronic diarrhea Non-PI (p < 0.001). Of the PI-patients, 3 had anti-CdtB, 5 antivinculin, none had both; while the Non-PI was only antivinculin positive.…”

Small Intestinal Bacterial Overgrowth—Pathophysiology and Its Implications for Definition and Management

“…That bacteria could injure the enteric neuromuscular apparatus and provide a basis for dysmotility and, potentially, SIBO, has been suggested to occur in one subtype of IBS, postinfection IBS. [136][137][138] Altered motility has also been invoked to explain the observation, by some, that those, with IBS, who exhale methane in preference to hydrogen on a breath test and are thus presumed to harbor methanogens, such as Methanobrevibacter smithii, are more likely to have IBS with constipation than diarrhea. 139,140 However, the association between methanogen overgrowth and constipation remains somewhat controversial.…”