Antibiotic Treatment Affects Intestinal Permeability and Gut Microbial Composition in Wistar Rats Dependent on Antibiotic Class.

Antibiotics are frequently administered orally to treat bacterial infections not necessarily related to the gastrointestinal system. This has adverse effects on the commensal gut microbial community, as it disrupts the intricate balance between specific bacterial groups within this ecosystem, potentially leading to dysbiosis. We hypothesized that modulation of community composition and function induced by antibiotics affects intestinal integrity depending on the antibiotic administered. To address this a total of 60 Wistar rats (housed in pairs with 6 cages per group) were dosed by oral gavage with either amoxicillin (AMX), cefotaxime (CTX), vancomycin (VAN), metronidazole (MTZ), or water (CON) daily for 10-11 days. Bacterial composition, alpha diversity and caecum short chain fatty acid levels were significantly affected by AMX, CTX and VAN, and varied among antibiotic treatments. A general decrease in diversity and an increase in the relative abundance of Proteobacteria was observed for all three antibiotics. Additionally, the relative abundance of Bifidobacteriaceae was increased in the CTX group and both Lactobacillaceae and Verrucomicrobiaceae were increased in the VAN group compared to the CON group. No changes in microbiota composition or function were observed following MTZ treatment. Intestinal permeability to 4 kDa FITC-dextran decreased after CTX and VAN treatment and increased following MTZ treatment. Plasma haptoglobin levels were increased by both AMX and CTX but no changes in expression of host tight junction genes were found in any treatment group. A strong correlation between the level of caecal succinate, the relative abundance of Clostridiaceae 1 family in the caecum, and the level of acute phase protein haptoglobin in blood plasma was observed. In conclusion, antibiotic-induced changes in microbiota may be linked to alterations in intestinal permeability, although the specific interactions remain to be elucidated as changes in permeability did not always result from major changes in microbiota and vice versa.

Dietary xylo-oligosaccharide stimulates intestinal bifidobacteria and lactobacilli but has limited effect on intestinal integrity in rats.

BACKGROUND: Consumption of prebiotics may modulate gut microbiota, subsequently affecting the bacterial composition, metabolite profile, and human health. Previous studies indicate that also changes in intestinal integrity may occur. In order to explore this further we have investigated the effect of the putative prebiotic xylo-oligosaccharides (XOS) on the gut microbiota and intestinal integrity in male Wistar rats. As changes in intestinal integrity may be related to the expected bifidogenic effect of XOS, we additionally addressed effects of supplementation with a commensal Bifidobacterium pseudolongum (BIF) isolated from the same breed of laboratory rats. RESULTS: Changes in faecal and caecal bacterial composition determined by 16S rRNA gene sequencing and quantitative PCR for selected bacterial groups revealed that the overall bacterial composition did not differ markedly between the control (CON), XOS, and BIF groups, when correcting for multiple comparisons. However as hypothesised, the relative abundance of Bifidobacterium spp. was increased in XOS-fed rats as compared to CON in faecal samples after the intervention. Also Lactobacillus spp. was increased in both the XOS and BIF groups in caecum content compared to CON. Intestinal permeability determined in vivo by FITC-dextran permeability and in vitro using extracted caecum water in trans-epithelial resistance (TER) assay showed no effect on intestinal integrity in either the XOS or the BIF groups. However, the expression of occludin, which is part of the tight junction complex, was increased in the XOS group compared to the CON group. CONCLUSIONS: Supplementation with XOS or a commensal Bifidobacterium pseudolongum had very limited effects on intestinal integrity in rats as only significant change in expression of a single tight junction protein gene was found for the XOS group.