IntroductionShort bowel syndrome (SBS) is the clinical state of malabsorption and malnutrition that occurs following small bowel resection (SBR). 1 Surgical resection of the small bowel may be required for the treatment of a range of conditions including congenital bowel abnormalities and necrotising enterocolitis in children and Crohn disease, trauma and malignancy in adults. Although the underlying reason for SBR between adults and children may differ, the clinical manifestations and consequences of SBS are similar. The symptoms of SBS reflect the loss of absorptive surface area and functional disturbance of the Background and objectives: Following small bowel resection (sBR), the luminal environment is altered, which contributes to clinical manifestations of short bowel syndrome (sBs) including malabsorption, mucosal inflammation and bacterial overgrowth. however, the impact of sBR on the colon has not been well-defined. The aims of this study were to characterize the colonic microbiota following sBR and to assess the impact of sBR on mucosal inflammation in the colon.Results: analysis of the colonic microbiota demonstrated that there was a significant level of dysbiosis both two and six weeks post-sBR, particularly in the phylum Firmicutes, coupled with a decrease in overall bacterial diversity in the colon. This decrease in diversity was associated with an increase in colonic inflammation six weeks post-surgery.Methods: Female (4-week old) piglets (5-6/group) received a 75% sBR, a transection (sham) or no surgery. compositional analysis of the colonic microbiota was performed by high-throughput sequencing, two-and six-weeks post-surgery. The gene expression of the pro-inflammatory cytokines interleukin (IL)-1β, IL-6, IL-8, IL-18 and tumor necrosis factor (TNF)-α in the colonic mucosa was assessed by qRT-pcR and the number of macrophages and percentage inducible nitric oxide synthase (iNOs) staining in the colonic epithelium were quantified by immunohistochemistry.Conclusions: sBR significantly decreased the diversity of the colonic microbiota and this was associated with an increase in colonic mucosal inflammation. This study supports the hypothesis that sBR has a significant impact on the colon and that this may play an important role in defining clinical outcome.
SummaryCitrobacter rodentium is a murine pathogen that transiently colonizes the lumen of the large intestine. C. rodentium induces colitis, but the relative importance and temporal induction of the T helper type 17 (Th17) and regulatory T cell (Treg) pathways in protection from the infection and inflammation have not been assessed. Our aim was to investigate the key immunological signalling events associated with successful clearance of C. rodentium. Mice were challenged with luminescent-tagged C. rodentium and killed at days 3 (early infection), 10 (peak infection) and 21 (late infection) postinfection. Bioluminescent imaging and bacterial culture determined levels of C. rodentium. Distal colon mRNA expression of interleukin (IL)-17, IL-6, IL-1b, tumour necrosis factor (TNF)-a, forkhead box P3 (FoxP3) and ghrelin were assessed using real-time polymerase chain reaction. Results were compared with age-matched non-infected mice. Low levels of C. rodentium were found at day 3, high levels at day 10, with clearance from the majority of the mice by day 21. In the distal colon, there was up-regulation of TNF-a and FoxP3 throughout the study and increases in IL-6 and IL-17 during the peak and late stages of infection. Ghrelin expression was increased at the peak and late stages of infection. This study has characterized changes to the T helper cell pathways, following the course of C. rodentium infection in mice. There were significant immunological changes, with up-regulation of the Th17 and Treg pathways in the distal colon and an increase in ghrelin expression compared with non-infected control mice. These changes may play a role in the pathology and clearance of C. rodentium.
T H 2-associated pathological immune activity that might underpin an increased risk of developing allergy or asthma? Clearly, the potential immune mechanisms underpinning the emerging post-COVID clinical entities will become increasingly more important to understand as the healthcare systems adapt to caring for large numbers of COVID-19 survivors during the coming months and years.
This study suggests that minor abdominal surgery in infants, results in long-term alteration of the colonic microbial composition and persistent gastrointestinal inflammation.
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