Impact of short-chain fatty acid supplementation on gut inflammation and microbiota composition in a murine colitis model.

Short-chain fatty acids (SCFAs) play a pivotal role in maintaining intestinal homeostasis. We aimed to investigate the effects of SCFA supplementation on gut inflammation and microbiota composition in a murine colitis model. Mice were fed with sodium butyrate or a mixture of SCFAs in the drinking water for 2 weeks, followed by 2% dextran sulfate sodium (DSS) for 7 d. After euthanasia, mouse colons were extracted to examine histological findings. Flow cytometry of the mouse colon tissues was performed to assess T cell differentiation. Changes in gut microbiota were assessed by high-throughput sequencing of the mouse feces. There were no significant differences in weight change, colonic length, or histologic inflammation score between the DSS, butyrate, and SCFA mix groups. However, flow cytometry revealed that both the expression of CD4+Foxp3+ regulatory T cells and of IL-17-producing T cells were increased in the butyrate and SCFA mix groups. Microbial compositions of the butyrate and SCFA mix groups were significantly different from those of the control and DSS groups in principal coordinate analysis. Relative abundances of the phyla Verrucomicrobia and Proteobacteria, species Akkermansia muciniphila and Escherichia fergusonii were increased in the butyrate and SCFA mix groups. Genera Roseburia and Lactobacillus showed a negative correlation with the degree of colitis, whereas genera Escherichia and Mucispirillum showed a positive correlation. SCFA supplementation did not result in a significant reduction in colon inflammation, but it promoted both regulatory T cell and IL-17-producing T cell expression, and increased both protective and aggressive gut microbiota.

The impact of gut microbiota manipulation with antibiotics on colon tumorigenesis in a murine model.

It has been suggested that manipulation of gut microbiota using antibiotics can inhibit colitis-associated colorectal cancer (CAC) in a mouse model. We investigated whether timing of gut microbial manipulation using antibiotics affects colon tumorigenesis in the azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced CAC model. CAC was induced in C57BL/6 mice by injection of 12.5 mg/kg AOM followed by three rounds of 1.7% DSS exposure. There were six groups based on timing of antibiotic administration. Colonic inflammation, proliferation, and tumorigenesis were evaluated after animal sacrifice. High-throughput sequencing of the mice feces was performed to characterize changes in gut microbiota. Full-time antibiotic treatment significantly decreased the number and size of tumors, histological scores, and expression of pro-inflammatory cytokines compared to the AOM/DSS group without antibiotic treatment. The early and late antibiotic groups, antibiotic administration from the first and second rounds of DSS to the end of the study, showed significantly lower histological scores and tumor burden. In contrast, the pretreatment antibiotic group, antibiotic administration from 3 weeks prior to AOM to the first round of DSS, did not exhibit decreased tumorigenesis. Principal coordinate analysis showed similar gut microbial community structures among the full-time, early, and late antibiotic groups, whereas other groups showed distinct gut microbial profiles. There was a positive correlation between number of tumors and number of operational taxonomic units. Colonic tumorigenesis was attenuated by antibiotic administration, except for that only prior to DSS administration, suggesting that gut microbial changes should be maintained throughout the entire period of inflammation to suppress tumorigenesis.

Characteristics and pathogenic role of adherent-invasive Escherichia coli in inflammatory bowel disease: Potential impact on clinical outcomes.

Adherent-invasive Escherichia coli (AIEC) has been reported as associated with the pathogenesis of inflammatory bowel disease (IBD). We aimed to investigate the characteristics of mucosa-associated E. coli and the clinical significance of AIEC in Korean IBD patients. E. coli strains were isolated from the mucosal tissues of 18 Crohn's disease (CD) patients, 24 ulcerative colitis (UC) patients, and 9 healthy controls (HC). Adhesion, invasion, and survival assays were performed to evaluate phenotypic features of E. coli isolates and to identify AIEC. The presence of virulence genes and cytokine expression were examined using PCR. In addition, data on IBD-related hospitalization were collected. A total of 59 E. coli strains were isolated (25 from CD, 27 from UC, and 7 from HC). The average levels of adhesion, invasion, and survival were higher in E. coli strains from IBD patients than those from HC (adhesion: 1.65 vs. 0.71, p = 0.046; invasion: 1.68 vs. 0.52, p = 0.039; survival: 519.55 vs. 47.55, p = 0.363). Prevalence of AIEC in HC, CD and UC patients was 22.2%, 38.9% and 37.5%, respectively. E. coli isolates from IBD patients had various virulence genes and were associated with increased expression of TNF-α and IL-17. IBD-related hospitalization within 3 years was 18.8% in patients with AIEC and 11.5% in patients without AIEC. E. coli strains from IBD patients showed high levels of adhesion, invasion, and survival. AIEC strains were identified in both CD and UC patients at a similar rate. AIEC may be associated with sustaining inflammation in the pre-existing inflammatory mucosa.