Possible role of the gut microbiome in mediating the beneficial effects of the six-herbal formulation STW 5-II on digestive health.

BACKGROUND: STW 5-II is a combination of six herbal extracts with clinically proven efficacy in functional dyspepsia (FD) and irritable bowel syndrome (IBS). STW 5-II contains a wide variety of secondary plant constituents that may interact with the human gut microbiome. In addition to complex carbohydrates, secondary plant metabolites, such as polyphenols, are known to exert prebiotic-like effects. PURPOSE: This study aimed to assess the bidirectional interactions between STW 5-II and the human gut microbiome. METHODS: STW 5-II was incubated with human fecal microbiota in a short-term colonic model. In the samples, the impact of STW 5-II on microbial fermentation capacity (pH, gas production), short chain fatty acid (SCFA) production, and microbial composition (Illumina 16S rRNA gene sequencing) was analyzed. In addition, the biotransformation of STW 5-II constituents by the fecal microbiota was assessed by UHPLCHRMS-based metabolite profiling. Furthermore, Caco-2/THP1 co-culture assay was used to explore the effect on gut barrier integrity and inflammatory markers. RESULTS: Fermentation of STW 5-II by fecal microbiota led to consistent changes in pH and gas production and increased production of SCFAs (acetate, propionate, and butyrate). STW 5-II promoted the enrichment of Bifidobacteriaceae, Lachnospiraceae, Ruminococcaceae, Erysipelotrichaceae, and Eggerthellaceae and suppressed the growth of pathogenic species from the Enterobacteriaceae family. In Caco2/THP1 culture, treatment with STW 5-II-incubated samples resulted in significantly increased transepithelial electrical resistance, indicating enhanced barrier function. Among inflammatory markers, STW 5-II-incubated samples increased LPS-induced secretion of the anti-inflammatory cytokine IL-10, as well as NF-κB activity, and significantly decreased the secretion of the pro-inflammatory chemokine MCP-1. UHPLCHRMS analysis identified 110 constituents of STW 5-II with changed levels during incubation with fecal microbiota: 63 constituents that were metabolized, 22 intermittently increased metabolites, and 25 final metabolites, including compounds with established anti-inflammatory activity, such as 18ß-glycyrrhetinic acid. CONCLUSION: These findings indicate a microbiome-mediated digestive health-promoting effect of STW 5-II via three different routes, namely enhanced microbial SCFA production, microbial production of potentially bioactive metabolites from STW 5-II constituents, and prebiotic-like action by promoting the proliferation/growth of beneficial bacteria.

Dual opposing actions of STW 5 on TRP receptors mediate neuronal desensitisation in vitro.

AIMS: STW 5 is an herbal drug combination used for the treatment of functional gastrointestinal disorders (FGIDs) with visceral hypersensitivity as the therapy-resistant hallmark. STW 5 has been clinically proven to alleviate visceral hypersensitivity-related symptoms, including abdominal pain, bloating, nausea, and early satiety. However, the molecular and cellular mechanisms underlying the antinociceptive action of STW 5 remain unknown. Here, we investigate the role of STW 5 in the calcium mobilisation of dorsal root ganglion (DRG) sensory neurons. MAIN METHODS: Calcium imaging experiments were performed with freshly dissociated cultured murine DRG neurons isolated from mice by microfluorometry. TRPA1-deficient DRGs, TRPV1-deficient DRGs, TRPA1/V1 double-deficient DRGs, and wild-type DRGs have been used to investigate the role of TRPs ion channels in mediating STW 5 action. KEY FINDINGS: STW 5 (1.74 and 5.8 mg/ml) induced calcium ion influx into DRG neurons in a concentration-dependent manner. Calcium transients were desensitised during repeated exposure to STW 5, an effect that was facilitated in TRPA1-deficient DRGs and less pronounced in TRPV1-deficient DRGs compared to wild-type (WT) DRGs. SIGNIFICANCE: Repeated exposure to STW 5 induced desensitisation of sensory neurons and may ultimately contribute to its proven clinical efficacy against sensory-related symptoms in patients with FGID, including abdominal pain, bloating, nausea, and early satiety. This effect is modulated by the two prominent irritant sensors in nociceptors, TRPA1 and TRPV1.

Simvastatin Use in Patients with Type 2 Diabetes Mellitus: The Effects on Oxidative Stress.

OBJECTIVES: Studies have shown that people with type 2 diabetes mellitus (T2DM) may develop atherosclerosis due to the disturbance in oxidative control and progressive dyslipidemia. Our study aimed to highlight the benefits of simvastatin treatment in improving serum lipids and reducing oxidative damage in patients with T2DM. METHODS: Our randomized control trial included 56 patients with T2DM and dyslipidemia. The participants were on glibenclamide (5mg/day) during the period of the study. The patients were divided into two study groups (groups 1 and 2). Group 1 was the control group and consisted of 31 patients. Group 2 consisted of 25 participants, who were given simvastatin 20mg tablet once daily for 12 weeks. The control group did not receive simvastatin. Both groups were followed-up for measurement of blood pressure, pulse rate, serum lipids, and parameters of oxidative stress. RESULTS: The simvastatin treated group showed a significant improvement with reduced erythrocyte glutathione compared to the control group (p<0.001). This was also associated with a significant reduction in erythrocyte malondialdehyde in the simvastatin treated group compared to the control group (p<0.001). Serum lipids reflected a similar improvement in the levels of erythrocyte malondialdehyde. CONCLUSION: Our study highlights the beneficial role of simvastatin in improving the degree of oxidative stress in patients with T2DM through its effects on serum lipids and lipid peroxidation.