Abstract
Background/AimsEnterochromaffin cells (EC cells) constitute the largest population of enteroendocrine cells and release serotonin (5-HT) in response to mechanical and chemical cues of the gastrointestinal tract (GIT). How EC cells respond to altered microbiota such as due to antibiotic treatments remain poorly understood. We hypothesized that the pacemaker channel HCN2 might contribute to the regulation of EC cells functions and their responses to antibiotics-induced changes in intestinal flora.MethodsMice were given either penicillin or streptomycin or both in drinking water for 10 consecutive days. The changes in the profile of short chain fatty acids (SCFAs) in the cecum following penicillin or streptomycin treatments were tested by GC-MS. Serum 5-HT content, whole intestinal transit time, fecal water content, cecum weight and expression of HCN2 and TPH1 in cecal mucosa were measured. Ivabradine (a HCN channels blocker) was used to explore the role of HCN2 in penicillin-induced changes in 5-HT availability and intestinal motility.ResultsHCN2 immunofluorescence was detected on intestinal EC cells. Both penicillin and streptomycin caused significant reduction in total SCFAs in the cecum, with the penicillin-treated group showing greater reductions in butyrate, isobutyrate and isovalerate levels than the streptomycin group. The expression of HCN2 was increased in the mice treated with penicillin, whereas TPH1 expression was increased in the mice treated with streptomycin. Mice treated with antibiotics all had larger and heavier cecum, elevated serum 5-HT level and increased fecal water content. Besides, mice treated with penicillin had prolonged intestinal transit time. Intraperitoneal injection of Ivabradine attenuated the effect of penicillin on serum 5-HT level, cecum size and weight, intestinal motility, and fecal water content.ConclusionDisruptions of the intestinal flora structure due to oral administration of penicillin may significantly increase serum 5-HT level and inhibit intestinal motility, at least partially through up-regulating the expression of HCN2. Oral administration of streptomycin may alter 5-HT availability by up-regulating TPH1 expression thus increasing synthesis of 5-HT. Alterations of intestinal flora composition due to exposure to different antibiotics may regulate 5-HT availability and intestinal motility through different mechanisms.
Highlights
The human gastrointestinal tract (GIT) is inhabited with tens of trillions of microorganisms (Kau et al, 2011)
There exist some Hyperpolarization-activated cyclic AMP-gated cation channel-2 (HCN2) positive cells in close proximity to 5-HT positive cells. This is consistent with previous findings that other enteroendocrine cells (e.g., GLP-1-secreting L cells) may express HCN2
These results suggest that the pacemaker channel HCN2 may play a role in regulation of 5-HT release from EC cells
Summary
The human gastrointestinal tract (GIT) is inhabited with tens of trillions of microorganisms (Kau et al, 2011). Increasing evidence suggest that the intestinal flora exert major influences on the host homeostasis. It was reported that the great majority of EC cells are scattered in the small intestine and colon in human beings; in rats, EC cells are mainly located in cecum and proximal colon (Qin et al, 2019). Recent data suggest that 5-HT released from EC cells to the lumen may modulate bacterial colonization in the gut (Fung et al, 2019). These data suggest that EC cells may be an important interface between the intestinal flora and the host
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