Role of Gut Microbial Dysbiosis, Subsequent Metabolite Secretion, and Signalling Pathways Focusing on Gut - Brain Axis and Pro-Inflammatory Cytokine Secretion in Infection - Constipation or Diarrhoea as the Initial Presenting Symptom - A Systematic Review

Abstract

The indigenous gut microbiota plays an important role in the maintenance of gut homeostasis. Dysbiosis, leading to the disruption of gut and overall homeostasis, leads to GI manifestations that hold key implications from One health perspective also. Here, we conducted a systematic review and meta-analysis of 35 horizontal studies investigating the association between gut microbiota, metabolites and signalling pathways and symptoms. In constipation, we observed correlation between increased fecal short chain fatty acids with Coprococcus, Fecalobacterium and Roseburia, increased ghrelin with H.pylori, increased methane with Methanobrevibacter and Methanogens and increased serotonin with Candida species. In diarrhoea, we observed correlation between increased fecal bile acids with increased Clostridia, decreased Blautia, Ruminococcaceae, increased Zonulin with E.coli and other Enterobactericiae, increased calprotectin with increased Hemophilus, Veillonella, decreased Clostridia, increased RA factor and Prevotella copri, increased purine/uric acid with Shigella and Enterococcus, increased leptin associated with E.histolytica and Strongyloides increased TNF-alpha, IL6, CRP and decreased IL10 with all pathobionts and increased Acetylcholine with B.subtilis rather than E.coli or S.aureus. Our study highlights the significance of gut microbial dysbiosis in infection-associated constipation or diarrhoea. It also emphasizes the need for multi-omics studies to overcome the shortcomings of the existing GI pathogen and GI microbiome panels. Additional longitudinal and interventional studies are warranted to develop additional diagnostic tools and novel therapeutic interventions for a holistic approach to maintain gut health and overall well-being.