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

Figures & data

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.^12–15 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.^71–73

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.

Table 1. Summary of studies examining the effects of probiotic co-supplementation to H. pylori eradication on the human gut microbiota.

Studies	Design	Eradication therapy	Probiotic strain/placebo	Methodology	Post-therapy evaluation (week after baseline)	Group specific alteration in the gut microbiota
						Antibiotic/placebo group	Probiotic group
Oh et al., 2016^Citation184	10 subjects in each group	Amoxicillin 1 g bid, clarithromycin 500 mg bid, lansoprazole 30 mg bid, 14 days	Streptococcus faecium 9 × 10^8, Bacillus subtilis 1 × 10^8, twice daily, 14 days	16S rRNA gene-pyrosequencing (V1-V3)	2 weeks	Citrobacter, Klebsiella, Pseudomonas, and Escherichia	NS
Oh et al., 2016^Citation185	Age: 44–55 3 subjects in each group	Amoxicillin 1 g bid, clarithromycin 500 mg bid, lansoprazole 30 mg bid, 14 days	Streptococcus faecium 9 × 10^8, Bacillus subtilis 1 × 10^8, twice daily, 14 days	Whole metagenome sequencing. Miseq platform (Illumina)	2 weeks	Klebsiella pneumoniae, Prevotella stercorea ↑	Lactobacillus ruminis, Escherichia coli, Bacteroides coprocola ↑
Chen et al., 2018^Citation99	Age: 18–70 Antibiotic group: 32 subjects Probiotic group: 31 subjects	Amoxicillin 1 g bid, colloidal bismuth pectin 400 mg bid, furazolidone 100 mg bid, pantoprazole 40 mg bid, 14 days	Clostridium butyricum CBM 588 40 mg tid, 14 days	16S rRNA gene (V3-V4). Miseq platform (Illumina)	2 weeks	Lentisphaerae ↓ Proteobacteria, Cyanobacteria ↑ Lactococcus raffinolactis, Lactobacillus sakei, Acinetobacter baumannii NIPH60 ↑	Fusobacteria, Tenericutes ↓ Actinobacteria, Cyanobacteria ↑
					8 weeks	NS	NS
Wu et al., 2019^Citation186	Age: 18–65 20 subjects with dudenal ulcer in each group	Amoxicillin 1 g bid, clarithromycin 500 mg bid, esomeprazole 20 mg bid, 14 days	Bacillus subtilis and Enterococcus faecium coated capsules 500 mg tid, 6 weeks following eradication	16S rDNA (V4)	2 weeks	Dialister	Actinomadura, Atopobium, Brevundimonas, Butyrivibrio, Coprococcus, Coraliomargarita, Corynebacterium, Desulfobacca, Desulfobulbus, Eggerthella, Faecalibacterium, GOUTA19, Helicobacter, Lewinella, Oscillospira, Rhodobacter, Rhodoplanes, Roseburia, Roseomonas, Rubrivivax, Thauera, Thiobacillus
					6 weeks	Dialister, Plesiomonas	Actinomadura, Anaerofilum, Candidatus Nitrososphaera, Candidatus Solibacter, Coprococcus, Coraliomargarita, Dechloromonas, Desulfomonile, Desulfobulbus, Dok59, Dorea, Leuconostoc, Luteimonas, Lewinella, Luteolibacter, Neisseria, Nitrosopumilus, Oscillospira, Parapedobacter, Planctomyces, Thauera, Syntrophobacter, Syntrophomonas, T78, Thermomonas, Thiobacillus
					10 weeks	Dialister	Achromobacter, Actinomyces, Cupriavidus, Bradyrhizobium, Candidatus Solibacter, Coprococcus, Chelativorans, Cetobacterium, Thiobacillus, Leuconostoc
Cárdenas et al., 2020^Citation187	Age: 18–55 Antibiotic group: 22 Probiotic group:16	Amoxicillin 1 g tid, tinidazole 1 g qd, omeprazole 40 mg bid, 14 days	Saccharomyces boulardii CNCM I-745 750 mg qd, 14 days	16S rRNA. Miseq platform (Illumina)	2 weeks	NS	Prevotella, Lachnospira, Ruminococcus ↓ Gammaproteobacteria ↑
					6 weeks	NS	Prevotella, Lachnospira, Ruminococcus ↓ Gammaproteobacteria ↑
Kakiuchi et al., 2020^Citation188	Antibiotic group: 26 Probiotic group: 23	Amoxicillin 750 mg bid, clarithromycin 400 mg bid, vonoprazan 20 mg bid, 7 days	BFR tid, 7 days	16S rDNA (V3-V4). Miseq platform (Illumina)	1 week	Collinsella, Bifidobacterium ↓	Blautia ↑
Tang et al., 2020^Citation189	Age: 18–65 Placebo group: 74 Probiotic group: 77	Amoxicillin 1 g bid, bismuth potassium citrate 220 mg bid, furazolidone 100 mg bid, esomeprazole 20 mg bid, 14 days	Enterococcus faecium 4.5 × 10^8 and Bacillus subtilis 5.0 × 10^7, or maltodextrin tid, 4 weeks	16S rRNA (V3-V4). Miseq platform (Illumina)	2 weeks	Dialister, Anaerotruncus, Megasphaera	Oscillospira, Citrobacter, Enterococcus
					4 weeks	Collinsella, Sutterella, Ruminococcus	Thermomonas, Bacillus, Lactobacillales, Enterococcus
					6 weeks	Coprococcus	Bulleidia, Anaerofustis
					8 weeks	Faecalibacterium	Phascolarctobacterium
Guillemard et al., 2021^Citation190	Age: 18–65 68 subjects in each group	Amoxicillin 1 g bid, clarithromycin 500 mg bid, pantoprazole 40 mg bid, 14 days	Lacticaseibacillus paracasei CNCM I-1518, Lacticaseibacillus paracasei CNCM I-3689, Lacticaseibacillus rhamnosus CNCM I-3690, Streptococcus thermophilus (CNCM I-2773, CNCM I-2835, CNCM I-2778), Lactobacillus delbrueckii subsp bulgaricus CNCM I-2787, 28 days	16S rRNA (V3-V4)	2 weeks	Enterorhabdus, Escherichia-Shigella, Roseburia, Leuconostoc, Akkermansia	Parasutterella, Howardella, Slackia, Desulfovibrio, Streptococcus, Lactobacillus, Alloprevotella, Succiniclasticum
					4 weeks	Enterorhabdus, Escherichia-Shigella, Roseburia, Megaphaera	Lactobacillus, Streptococcus, Butyricimonas, Methanobrevibacter, Pediococcus, Parasutterella, Howardella, Slackia, Desulfovibrio
					6 weeks	Enterorhabdus, Escherichia-Shigella, Roseburia, Megaphaera, Klebsiella, Succiniclasticum	Pediococcus, Parasutterella, Howardella, Slackia, Desulfovibrio, Megamonas, Lachnospira, Catenibacterium, Butyricimonas
Yang et al., 2021^Citation191	Age: 18–70 94 subjects in each group	Amoxicillin 1 g bid, clarithromycin 500 mg bid, esomeprazole 20 mg bid, 14 days	Non-viable Lactobacillus reuteri DSM17648 2 × 10^10 bid, 2 weeks pre-treatment	16S rRNA (V3-V4)	2 weeks	Proteobacteria Escherichia-Shigella	Bacteroidota Bacteroides, Fusicatenibacter
					8 weeks	NS	Faecalibacterium, Subdoligranulum
Yuan et al., 2021^Citation192	Age: 18–30 Antibiotic group: 34 Probiotic group: 31	Amoxicillin 1 g bid, clarithromycin 500 mg bid, potassium bismuth citrate 200 mg bid, esomeprazole 20 mg bid, 14 days	Bifidobacterium tetravaccine tablets included B. infantis >0.5 × 10^6 CFU/tablet, L. acidophilus >0.5 × 10^6 CFU/tablet, E. faecalis >0.5 × 10^6 CFU/tablet, B. cereus >0.5 × 10^5 CFU/tablet, three tablets each time, three times a day, 14 days	16S rRNA (V3-V4). Miseq platform (Illumina)	10 weeks	Gastric mucosa: Erysipelatoclostridium, Ralstonia	Gastric mucosa: Lachnospiraceae UCG 006
						Gastric juice: Proteobacteria was more abundnt than Firmicutes Fusobacterium, Mycoplasma (Tenericutes), Leptotrichia, Campylobacter	Gastric juice: Firmicutes was more abundnt than Proteobacteria Ruminococcaceae UCG014, Eubacterium ventriosum

qd, once a day; bid, twice a day; tid, three times a day; NS, not significant

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Data availability statement

Data sharing is not applicable to this article as no new data were created or analyzed in this work.