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The long-term consequences of antibiotic therapy: Role of colonic short-chain fatty acids (SCFA) system and intestinal barrier integrity.

ABSTRACT: Epidemiological studies revealed that antibiotics exposure increases a risk of inflammatory bowel diseases (IBD) development. It remained largely unknown how antibiotic-induced dysbiosis confers the risk for enhanced inflammatory response. The aim of the present study was to test the hypothesis that SCFAs, their receptors and transporters mediate the antibiotic long-term effects on the functional state of colonic mucosa and susceptibility to the experimental colitis. Male Wistar rats were treated daily for 14 days with antibiotic ceftriaxone (300 mg/kg, i.m.) or vehicle; euthanized by CO2 inhalation followed by cervical dislocation in 1, 14 or 56 days after antibiotic withdrawal. We found increased cecum weight and sustained changes in microbiota composition after ceftriaxone treatment with increased number of conditionally pathogenic enterobacteria, E. coli, Clostridium, Staphylococcus spp. and hemolytic bacteria even at 56 days after antibiotic withdrawal. The concentration of SCFAs was decreased after ceftriaxone withdrawal. We found decreased immunoreactivity of the FFA2, FFA3 receptors, SMCT1 and increased MCT1 & MCT4 transporters of SCFAs in colon mucosa. These changes evoked a significant shift in colonic mucosal homeostasis: the disturbance of oxidant-antioxidant balance; activation of redox-sensitive transcription factor HIF1? and ERK1/2 MAP kinase; increased colonic epithelial permeability and bacterial translocation to blood; morphological remodeling of the colonic tissue. Ceftriaxone pretreatment significantly reinforced inflammation during experimental colitis 56 days after ceftriaxone withdrawal, which was confirmed by increased histopathology of colitis, Goblet cell dysfunction, colonic dilatation and wall thickening, and increased serum levels of inflammatory cytokines (TNF-? and IL-10). Since the recognition of the importance of microbiota metabolic activity rather than their composition in the development of inflammatory disorders, e.g. IBD, the present study is the first report on the role of the SCFA system in the long lasting side effects of antibiotic treatment and its implication in IBD development.

SUBMITTER: Holota Y

PROVIDER: S-EPMC6705842 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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The long-term consequences of antibiotic therapy: Role of colonic short-chain fatty acids (SCFA) system and intestinal barrier integrity.

Holota Yuliia Y Dovbynchuk Taisa T Kaji Izumi I Vareniuk Igor I Dzyubenko Natalia N Chervinska Tetiana T Zakordonets Liudmyla L Stetska Viktoria V Ostapchenko Liudmyla L Serhiychuk Tetiana T Tolstanova Ganna G

PloS one 20190822 8

Epidemiological studies revealed that antibiotics exposure increases a risk of inflammatory bowel diseases (IBD) development. It remained largely unknown how antibiotic-induced dysbiosis confers the risk for enhanced inflammatory response. The aim of the present study was to test the hypothesis that SCFAs, their receptors and transporters mediate the antibiotic long-term effects on the functional state of colonic mucosa and susceptibility to the experimental colitis. Male Wistar rats were treate ...[more]

PMID: 31437166

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Project description:Impaired intestinal barrier plays an important role in the pathogenesis of hypertension primarily through promoting the development of chronic low-grade inflammation. Baicalin is the major flavonoid component of Scutellaria baicalensis Georgi, a medicinal plant commonly used for the treatment of inflammatory intestinal disorders and hypertension in traditional Chinese medicine. However, it remains to be elucidated whether baicalin alleviates hypertension-associated intestinal barrier impairment. The current study thus investigated the effects of baicalin on the intestinal barrier integrity, the intestinal expression of genes encoding proinflammatory factors and tight junction proteins, the serum levels of the inflammatory markers, the amount of fecal short-chain fatty acids (SCFAs) and the abundance of SCFAs-producing bacteria in the spontaneously hypertensive rats (SHRs). The results showed that baicalin alleviated the pathological lesions in the ilium and the proximal colon in the SHRs. Baicalin treatment resulted in decreased ileal and colonic expression of proinflammatory genes in the SHRs. In addition, baicalin treatment attenuated hypertension-associated intestinal hyperpermeability and decreased the serum levels of inflammatory indicators such as high-sensitivity C-reactive protein (hs-CRP), interleukin 1 beta, and IL-6 in the SHRs. The protective effect of baicalin on the intestinal integrity was also supported by well-preserved intestinal ultrastructure and increased intestinal expression of genes encoding tight junction proteins such as zonula occludens-1 (ZO-1), cingulin, and occludin in the SHRs. Lastly, baicalin treatment increased the amount of fecal SCFAs and the abundance of SCFAs-producing bacteria in the SHRs. In conclusion, the work here provides for the first time the morphological, biochemical, and molecular evidence supporting the protective effects of baicalin on the intestinal integrity in the SHRs, which may help better understand the therapeutic effects of S. baicalensis Georgi in the treatment of hypertension.

Dataset Information

The long-term consequences of antibiotic therapy: Role of colonic short-chain fatty acids (SCFA) system and intestinal barrier integrity.

Publications

The long-term consequences of antibiotic therapy: Role of colonic short-chain fatty acids (SCFA) system and intestinal barrier integrity.

Similar Datasets

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