Molecular signalling during cross talk between gut brain axis regulation and progression of irritable bowel syndrome: A comprehensive review

Table 1 Types of regulation of serotonergic (5-Hydroxytryptamine) pathway by specific enteric microbiota in gastrointestinal tract

Microbiota spp.	5-HT pathway	Mechanisms of action and observations	Ref.
Akkermansia muciniphila (Amuc_1100)	Upregulation	Promote intestinal 5-HT biosynthesis and extracellular availability through TLR2 signalling	[129]
Akkermansia muciniphila (extracellular vesicles)	Upregulation	Increase expression of the Htr4 gene, and decreases expression of the Htr2B, Htr3B, and Htr7 genes	[129]
Bacteriodes thetaiotaomicron	Upregulation	Restore 5-HT+ EC cells and shape EC networks in the GI tract of GF mice by producing SCFAs	[130]
Bifidobacterium dentium	Upregulation	Increase intestinal 5-HT level; expressions of 5-HTra receptors 2a and 4, and SERT by producing acetate	[131]
Bifidobacterium longum and	Downregulation	Upregulate SERT expression	[132]
Lactobacillus acidophilus
Bifidobacterium pseudolongum	Downregulation	Diminish EC cells	[133]
Clostridium ramosum	Upregulation	Promote 5-HT synthesis in colonic EC cells and program differentiation of intestinal stem progenitors toward a secretory 5-HT-producing lineage	[134]
Corynebacterium spp., Enterococcus spp., Streptococcus spp.	Upregulation	Enable the direct production of 5-HT	[135]
Escherichia coli Nissle 1917	Upregulation	Enhance 5-HT bioavailability in ileal tissue through interaction with compounds secreted from host tissue	[136]
Indigenous spore-forming bacteria	Upregulation	Enhance colonic 5-HT pathway by upregulation of Htr4	[137]
Lactobacillus acidophilus	Down regulation	Upregulate SERT expression	[138]
Lactobacillus plantarum IS-10506	Upregulation	Increase gut 5-HT production along with brain 5-HTT, neurotrophin, and brain-derived neurotrophic factor	[139]
Lactobacillus plantarum PS128	Upregulation	Increase 5-HT+ cells in the gut and alter expression levels of Tph1, Chga, Slc6a4, and Htr4	[140]
Lactobacillus rhamnosus	Down regulation	Upregulate gene and protein level of SERT	[141]
SadA-expressing Staphylococci, Trichinella spiralis and Campylobacter jejuni (pathogens)	Upregulation	Promote converting 5-HTP into 5-HT; increase EC cell number and reduce SERT expression	[141]

5-HT: 5-Hydroxytryptamine; 5-HTP: 5-Hydroxytryptophan; EC: Enterochromaffin cell; SERT: Serotonin transporters.

Table 2 Various therapies prescribed for the treatment of irritable bowel syndrome along with their possible mode of action

Therapy	Description	Proposed mechanism(s) of action
Prebiotics	Ingested compounds targeted to stimulate gut microbiota	Mechanism of action undefined, but may include: Anti-inflammatory effects; inhibition of pathogen adherence; and growth of intestinal mucosal layer
Probiotics	Ingested microorganisms (e.g., bacteria)	Mechanism of action undefined, but may include: Inhibition of pathogenic microorganism colonization; support intestinal barrier integrity and function; production of beneficial micronutrients; and activation and augmentation of the enteric nervous system
Rifaximin	Nonabsorbable, bile-soluble antibiotic indicated for the treatment of adults with IBS-D	Antibacterial against Gram-positive and Gram-negative bacteria: Modulation of gut-immune signalling; inhibition of bacterial translocation; SIBO eradication (in some patients); causing decreases in GI methane concentrations in combination; and with the antibiotic neomycin (in patients with IBS-C)
SBI	Prescription medical food for patients with IBS-D	Modulation of gut microbiota: Causing decreases in GI permeability
SYN-010	Derivative of the HMG-CoA reductase inhibitor lovastatin lactone; currently in development for the treatment of patients with IBS-C	Inhibition of methane production by Methanobrevibacter smithii
Dietary modification	Variable; one example is the low FODMAP diet	Causing decreases in GI gas production
		Causing decreases in intra-luminal fluid production

FODMAP: Fermentable oligo-, di-, monosaccharides and polyols; GI: Gastrointestinal; HMG-CoA: 3-hydroxy-3-methylglutaryl-coenzyme A; IBS-C: Constipation-predominant irritable bowel syndrome; IBS-D: Diarrhea-predominant irritable bowel syndrome; SBI: Serum-derived bovine immunoglobulin; SIBO: Small intestinal bacterial overgrowth.