The double-edged sword of probiotic supplementation on gut microbiota structure in Helicobacter pylori management

Abstract

As Helicobacter pylori management has become more challenging and less efficient over the last decade, the interest in innovative interventions is growing by the day. Probiotic co-supplementation to antibiotic therapies is reported in several studies, presenting a moderate reduction in drug-related side effects and a promotion in positive treatment outcomes. However, the significance of gut microbiota involvement in the competence of probiotic co-supplementation is emphasized by a few researchers, indicating the alteration in the host gastrointestinal microbiota following probiotic and drug uptake. Due to the lack of long-term follow-up studies to determine the efficiency of probiotic intervention in H. pylori eradication, and the delicate interaction of the gut microbiota with the host wellness, this review aims to discuss the gut microbiota alteration by probiotic co-supplementation in H. pylori management to predict the comprehensive effectiveness of probiotic oral administration.Abbreviations: acyl-CoA- acyl-coenzyme A; AMP- antimicrobial peptide; AMPK- AMP-activated protein kinase; AP-1- activator protein 1; BA- bile acid; BAR- bile acid receptor; BCAA- branched-chain amino acid; C2- acetate; C3- propionate; C4- butyrate; C5- valeric acid; CagA- Cytotoxin-associated gene A; cAMP- cyclic adenosine monophosphate; CD- Crohn's disease; CDI- C. difficile infection; COX-2- cyclooxygenase-2; DC- dendritic cell; EMT- epithelial-mesenchymal transition; FMO- flavin monooxygenases; FXR- farnesoid X receptor; GPBAR1- G-protein-coupled bile acid receptor 1; GPR4- G protein-coupled receptor 4; H2O2- hydrogen peroxide; HCC- hepatocellular carcinoma; HSC- hepatic stellate cell; IBD- inflammatory bowel disease; IBS- irritable bowel syndrome; IFN-γ- interferon-gamma; IgA immunoglobulin A; IL- interleukin; iNOS- induced nitric oxide synthase; JAK1- janus kinase 1; JAM-A- junctional adhesion molecule A; LAB- lactic acid bacteria; LPS- lipopolysaccharide; MALT- mucosa-associated lymphoid tissue; MAMP- microbe-associated molecular pattern; MCP-1- monocyte chemoattractant protein-1; MDR- multiple drug resistance; mTOR- mammalian target of rapamycin; MUC- mucin; NAFLD- nonalcoholic fatty liver disease; NF-κB- nuclear factor kappa B; NK- natural killer; NLRP3- NLR family pyrin domain containing 3; NOC- N-nitroso compounds; NOD- nucleotide-binding oligomerization domain; PICRUSt- phylogenetic investigation of communities by reconstruction of unobserved states; PRR- pattern recognition receptor; RA- retinoic acid; RNS- reactive nitrogen species; ROS- reactive oxygen species; rRNA- ribosomal RNA; SCFA- short-chain fatty acids; SDR- single drug resistance; SIgA- secretory immunoglobulin A; STAT3- signal transducer and activator of transcription 3; T1D- type 1 diabetes; T2D- type 2 diabetes; Th17- T helper 17; TLR- toll-like receptor; TMAO- trimethylamine N-oxide; TML- trimethyllysine; TNF-α- tumor necrosis factor-alpha; Tr1- type 1 regulatory T cell; Treg- regulatory T cell; UC- ulcerative colitis; VacA- Vacuolating toxin A.

Keywords: Helicobacter pylori; gastric cancer; gastrointestinal microbiota; gut metabolome; intestinal homeostasis; metabolic disorder; probiotic supplementation.

Figure 1.

The main genera and total abundance of bacteria vary along the gastrointestinal tract. The colon is characterized by low levels of oxygen as well as the presence of enormous numbers and species of bacteria. On the other hand, the microbial composition and metabolite concentration of stool samples are distinguished from gut biopsies, in which the bacteria and the fungi constitute the majority and minority of total fecal DNA, respectively. Fecal concentration of SCFAs are also demonstrated as they might be considered key regulators of the intestinal homeostasis.

Figure 2.

The interplay between the gut metabolome, H. pylori, and the host immune system. H. pylori induces chronic gastric inflammation through the activation of transcriptional factors such as NF-κB. By stimulating the production of BCAA from the gut microbiota, H. pylori activates the mTORC1 complex and ultimately inhibits autophagic response. H. pylori further disrupts the integrity of the gastric epithelial barrier by suppressing the expression of tight junction proteins. On the other hand, microbiota production of SCFAs and secondary bile acids modulate gastric inflammation and immune system activation by reducing NF-κB activation, promoting the secretion of anti-inflammatory cytokines, AMPs, and IgA, and preserving the integrity of the gut barrier.

Figure 3.

The progression of chronic gastritis toward gastric carcinoma has been characterized by the reduction in the Helicobacter genus, overgrowth of opportunistic bacteria, increased apoptosis, necrosis, and collagen production, changes in the cytoskeleton and polarity of the gastric epithelium, and gradual suppression of gastric acidity. The main mechanisms of action through which H. pylori virulence factors promote the risk of developing gastric cancer are further depicted.

Figure 4.

The interplay between probiotic strains, H. pylori, and the host immune system. Several probiotic strains can directly eliminate H. pylori cells by producing bacteriocins, siderophore, hydrogen peroxide, biosurfactant, lactic acid, and SCFAs. Probiotic bacteria can retain the activity of the gut barrier by stimulating the production of mucin and tight junction proteins. Certain probiotic species preserve the inherent structure of the gut microbiota by increasing the concentration of AMPs, peptidoglycan hydrolase, and exopolysaccharides. Furthermore, several probiotic bacteria regulate the host inflammatory response and prevent the development of chronic inflammation.