Background: Extensive evidence suggests that gut microbiota may interact with the kidneys and play central roles in the pathogenesis of disease. However, the association of gut microbiota-kidneys in diarrhea remains unclear. Methods: A diarrhea mouse model was constructed by combining adenine with Folium sennae. We analyzed the characteristics of the gut content microbiota and short chain fatty acids (SCFAs); and explored the potential link between gut content microbiota, SCFAs, intestinal inflammatory response and kidney function. Results: Characteristic bacteria Lactobacillus intestinalis and Bacteroides acidifaciens were enriched in the gut contents of mice. The productions of SCFAs were remarkably inhibited. Model mice presented an increased trend of creatinine (Cr), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), a decreased trend of blood urea nitrogen (BUN) and secretory immunoglobulin A (SIgA). The pathological analysis proved obvious damage to the kidney structure. Lactobacillus intestinalis and Bacteroides acidifaciens exisited in the correlations with acetic acid, intestinal inflammatory response and kidney function. Conclusions: Adenine combined with Folium sennae-induced diarrhea, altered the structure and function of the gut content microbiota in mice, causing the enrichment of the characteristic bacteria Lactobacillus intestinalis and Bacteroides acidifaciens. The interactions between Lactobacillus intestinalis, Bacteroides acidifaciens and acetic acid, intestinal inflammation, and kidney function might be involved in the process of gut-kidney impairment in adenine, combined with Folium sennae-induced diarrhea.

Gut microbiota-derived trimethylamine N-oxide (TMAO) has been implicated in both intestinal and renal diseases; however, its specific role in modulating gut–kidney interactions remains unclear. This study aimed to investigate the effects of TMAO on gut–kidney crosstalk using a mouse model of diarrhea. Mice were divided into four groups: normal, model, TMAO, and TMAO + model. The normal group received sterile water, while the other groups were administered adenine + Folium sennae, TMAO, or a combination of TMAO and adenine + Folium sennae. Samples were collected to assess morphological changes in the colon and kidney, evaluate the colonic mucosal barrier and renal function, and measure NLRP3 inflammasome activity and inflammatory cytokine levels in colonic and renal tissues. TMAO levels and the gut microbiota composition were analyzed using 16S rRNA sequencing. The model group exhibited altered stool morphology, which was further aggravated by TMAO intervention. Both the model and TMAO + model groups exhibited significant damage to intestinal and renal tissues, along with compromised intestinal mucosal barriers and impaired renal function compared to controls. Inflammatory markers were elevated in these groups, with the TMAO + model group showing the most pronounced increases. Correlation analysis indicated significant relationships among TMAO levels, inflammasome activation, and inflammatory cytokines. The genera Mucispirillum and Anaerotruncus negatively correlated with TMAO, whereas Parabacteroides and Parasutterella genera positively correlated with TMAO. In conclusion, TMAO plays a critical role in modulating gut–kidney crosstalk by promoting inflammation, disrupting mucosal and renal integrity, and altering the gut microbial ecosystem.

The dried ripe seeds and pericarp of Areca catechu L., a palm species, possess significant economic value. Masticating betel nut is also a long-standing and widely prevalent lifestyle habit rooted in history, known for its stimulating effect. This effect stems primarily from arecoline, the principal active compound in betel nut. This study investigates the potential mechanisms underlying the stimulating effects of arecoline, focusing on neurotransmitters, neurotrophic factors, and the microecosystem in multi-ecological intestinal sites. After arecoline intervention in mice, significant changes were observed in locomotor activity. The levels of dopamine (DA) in liver tissue and 5-hydroxytryptamine (5-HT) in brain tissue were significantly reduced. There was a significant increase in microbial activity in the feces and in the level of n-valeric acid in the intestinal content. At the genus level, the relative abundance of Clostridium was significantly reduced, whereas the relative abundances of Helicobacter and Aquincola were markedly increased. Helicobacter, Aquincola, Faecalibaculum, and Liquorilactobacillus were signature genera in the arecoline-treated group. The 5-HT level was significantly negatively correlated with the abundance of the signature genera Aquincola, Helicobacter, and Liquorilactobacillus in the arecoline group. The ingestion of arecoline can alter the behavioral patterns of mice, causing significant changes in the 5-HT levels in brain tissue and exerting regulatory effects on the microecosystem in multi-ecological intestinal sites. These findings will provide a reference for the future development and utilization of betel nut.