Colorectal cancer (CRC) is a growing public health concern due to its rising incidence and high rate of cancer-associated deaths. Emerging evidence suggests that gut microbiota and their metabolites are critically involved in the initiation and advancement of CRC. These metabolites, which originate from the breakdown of nutrients from food and host-related substances through microbial activity in the gut, can profoundly influence tumor formation. In addition to well-studied compounds such as short-chain fatty acids (SCFAs), bile acids (BAs), tryptophan metabolites, and polyamines, this review highlights emerging metabolites—including hydrogen sulfide (H₂S) and formate—that have recently drawn attention for their roles in colorectal carcinogenesis. We also incorporate recent mechanistic insights, such as butyrate-induced ferroptosis and H₂S-mediated protein persulfidation, to illustrate how microbial metabolites influence cancer cell metabolism. Moreover, the potential of microbial metabolites as biomarkers for early diagnosis and prognosis of CRC is discussed. Therapeutic strategies targeting microbial metabolites—such as dietary modulation, combination therapies, fecal microbiota transplantation (FMT), and phage therapy—are also reviewed. By providing a comprehensive and up-to-date overview of microbial metabolic networks associated with CRC, this review underscores the critical functions of gut microbial metabolites in tumorigenesis, offering novel insights into their utility as diagnostic and prognostic biomarkers, as well as promising therapeutic targets.

Objective: To examine the causal effect of potentially modifiable risk factors contributing to migraine pathogenesis.Methods: We performed Mendelian randomization analyses and acquired data from United Kingdom Biobank, FinnGen Biobank, and the MRC IEU OpenGWAS data infrastructure. An inverse-variance weighted (IVW) model was used to examine the relationship between 51 potentially modifiable risk factors and migraine in 3215 participants with migraine without aura (MwoA), 3541 participants with migraine with aura (MwA), and 176,107 controls. We adopted a Bonferroni-corrected threshold of p = 9.8 × 10–4 (.05 divided by 51 exposures) as a sign of significant effect, and a p < .05 was considered as the sign of a suggestive association.Results: More years of schooling significantly correlated with lower odds of MwoA pathogenesis (OR .57 [95%CI .44 to .75], p < .0001). More vitamin B12 intake (OR .49 [95%CI .24 to .99], p = .046) and lower level of stress [OR 8.17 (95%CI 1.5 to 44.36), p = .015] or anxiety disorder (OR 1.92 × 109 [95%CI 8.76 to 4.23*1017], p = .029) were suggestive to be correlated lower odds of MwoA pathogenesis. More coffee intake (OR .39 [95%CI .22 to .7], p = .001), lower level of eicosapentaenoic acid status (OR 2.54 [95%CI 1.03 to 6.26], p = .043), and more light physical activity (OR .09 [95%CI .01 to .94], p = .046) were suggestive to be associated with lower odds of MwA.Conclusion: The years of schooling, light physical activity, vitamin B12 intake, and coffee intake were the protective factors for migraine; stress, anxiety, and eicosapentaenoic acid status were harmful factors. Interventions could be developed based on modifying these factors for migraine prophylaxis.

Objective: Previous systematic reviews demonstrated a potentially beneficial effect of probiotics on irritable bowel syndrome (IBS). However, these studies are either affected by the inclusion of insufficient trials or by the problem of dependent data across multiple outcomes, and an overall effect size has not been provided. We aimed to determine the effect of probiotics on IBS through a three-level meta-analysis and clarify potential effect moderators. Methods: We searched MEDLINE, Embase, and Web of Science, screening for randomized controlled trials (RCTs) that examine the effect of probiotics on IBS. The primary outcome was the improvement in the severity of global IBS symptoms at the end of treatment. The secondary outcomes were the improvement in abdominal pain and the quality of life. The effect sizes of the probiotics were measured by using the standardized mean difference (SMD) and pooled by a three-level meta-analysis model. Results: We included 72 RCTs in the analysis. The meta-analysis showed significantly better overall effect of probiotics than placebo on the global IBS symptoms (SMD −0.55, 95% CI −0.76 to −0.34, P<0.001), abdominal pain (SMD −0.89, 95% CI −1.29 to −0.5, P<0.001) and quality of life (SMD 0.99, 95% CI 0.45 to 1.54, P<0.001), respectively. Moderator analysis found that a treatment duration shorter than 4 weeks was associated with a larger effect size in all the outcomes, and Bacillus probiotics had better improvement on the abdominal pain. Conclusions: Probiotics had a short-term effect and a medium effect size on the global IBS symptoms. Treatment duration and types of probiotics affected the effect size of probiotics, and shorter durations and Bacillus probiotics were associated with better treatment effects. Registration: Open Science Framework.

Background: Probiotic and low fermentable oligosaccharide, disaccharide, monosaccharide, and polyol (FODMAP) diet are two commonly used management approaches for patients with irritable bowel syndrome (IBS). We aimed to evaluate the most effective combinations and components among different probiotics or low FODMAP diet through component network meta-analysis (NMA).Methods: We searched Embase, Ovid Medline, and Web of Science from inception to 21 January 2021. Randomized controlled trials (RCTs) examining the efficacy of probiotics and low FODMAP diet for IBS were included, with placebo, sham diet, or conventional treatments as controls. Binary outcomes were compared among treatments using the relative ratio (RR). A minimally contextualized framework recommended by the GRADE group was used to evaluate the certainty of evidence. The primary efficacy outcome was the relief of global IBS symptoms, and the secondary efficacy outcome was the reduction in IBS symptom scores or abdominal pain scores.Key Results: We included 76 RCTs (n = 8058) after screening 1940 articles. Eight RCTs were classified as low risk of bias. Standard network meta-analysis (NMA) showed that Lactobacillus (RR 1.74, 95% CI 1.22–2.48) and Bifidobacterium (RR 1.76, 95% CI 1.01–3.07) were the most effective for the primary efficacy outcome (high certainty evidence); component NMA showed that Bacillus (RR 5.67, 95% CI 1.88 to 17.08, p = 0.002) and Lactobacillus (RR 1.42, 95% CI 1.07 to 1.91, p = 0.017) were among the most effective components. The results of standard NMA and CNMA analysis of the improvement of overall IBS symptom scores or abdominal pain scores were consistent with this finding.Conclusion:Lactobacillus was the most effective component for the relief of IBS symptoms; Bifidobacterium and Bacillus were possibly effective and need further verification.Systematic Review Registration: website, identifier registration number.