Roles of short-chain fatty acid in antibiotic-associated diarrhea and its mechanism

Objective To investigate the effect of short-chain fatty acid (SCFAs) on antibiotic-associated diarrhea(AAD) and its mechanism.

Methods AAD models were established by giving lincomycin injection fluid by gavage and randomly divided into AAD group, low dose SCFAs group and high dose SCFAs group. The normal rats were included in control group, with 6 rats in per group. The control and AAD groups were treated with 10 mL/(kg·d) normal saline, while the low dose and high dose SCFAs groups were gavaged SCFAsa mixture of acetic acid, propionic acid and butyric acid, at a ratio of 3∶1∶1 for 100 mg/(kg·d) for 100, 150 mg/(kg·d), respectively. All groups were treated for 15 days. The diarrhea, changes of colonic tissue, levels of inflammatory factors and gut microbiota were recorded and compared in each group.

Results The rats in the control group were normal in water and food intake, and had normal stools and urine. The rats in the AAD group showed increased water intake, decreased food intake, loose and irregular feces. The rats in the low dose SCFAs group and high dose SCFAs group had less intake of diet, normal water intake and occasional soft stools. There was a statistically significant difference in body weight among these groups at 15 d after treatment(P<0.05). The colonic tissue showed that the mucosal epithelial structure was intact. Severe inflammatory cell infiltration in mucous lamina propria was observed in the AAD group, and the mucosal epithelium structure was intact in low dose SCFAs group and high dose SCFAs group, and inflammatory cell infiltration was less than that in the AAD group. Compared with the control group, the colon length, the number of Goblet cell and the proportion of Gram-negative bacilli in the colon tissue of the AAD group were decreased, while the relative expression of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-1β(IL-1β) mRNA, spleen index, and proportion of Gram-positive bacilli were increased in the AAD group(P<0.05). Compared with AAD group, the length of colon, the number of Goblet cell in colon tissue of the low dose and high dose SCFAs groups were increased, the spleen index was decreased, and IL-6, TNF-α, IL-1β mRNA were reduced (P<0.05), showing a SCFA dose-dependent trend.

Conclusion SCFAs is helpful to promote the recovery of intestinal barrier function of AAD, which may be related to functions of SCFA, including regulating inflammatory cytokines, changing the composition of Gut microbiota and alleviating the intestinal mucosal damage caused by AAD.