Probiotics Rebuild the Gut and Stomach Microbiome After H. pylori Eradication Therapy

Antibiotics that cure one of the world’s most common bacterial infections may leave the digestive system in ecological ruins, but a new study in mice suggests that a carefully timed probiotic regimen can help restore the damage. In research published in the journal Gut Pathogens, a team at the First Affiliated Hospital of Nanchang University in China reports that supplementation with two specific probiotic strains significantly accelerates the recovery of both the gastric and intestinal microbiota after standard eradication therapy for Helicobacter pylori, the bacterium that causes most peptic ulcers and raises the risk of stomach cancer.

The study addresses a persistent clinical dilemma. Triple therapy, the standard combination of a proton pump inhibitor such as omeprazole with the antibiotics clarithromycin and metronidazole, is effective at clearing H. pylori, but it delivers a broad antimicrobial assault on the trillions of microbes that inhabit the gastrointestinal tract. Previous work has documented dysbiosis after eradication, yet most studies have examined either the stomach or the gut in isolation. The new research takes a paired approach, sequencing microbial communities from both compartments in the same animals to capture how the two ecosystems interact and recover together.

The researchers used C57BL/6 mice, a standard laboratory strain, divided into five experimental groups. One group remained uninfected as controls. A second was infected with H. pylori PMSS1, a well-characterized laboratory strain. A third received two weeks of triple therapy after infection. A fourth was allowed to recover spontaneously for four weeks after eradication, while the fifth received probiotic supplementation during the recovery period using Enterococcus faecium R0026 and Bacillus subtilis R0179, two strains with documented safety records. The team then performed 16S rRNA gene sequencing on paired gastric and fecal samples, constructing cross-compartment co-occurrence networks and predicted functional profiles to map the microbial landscape in detail.

The baseline findings confirmed that H. pylori infection itself is not a passive presence. The bacterium reshaped both the gastric and intestinal microbiota, with the more pronounced perturbation occurring in the stomach, its primary niche. This matters because the gastric microbiota has historically been understudied, long dismissed as too acidic to host a meaningful community. The results reinforce a growing consensus that the stomach maintains a distinct microbial ecosystem, one that can be destabilized by both pathogens and the drugs used to eliminate them.

The most dramatic disruption, however, came not from the infection but from its cure. Eradication therapy triggered severe, compartment-specific dysbiosis that predominantly damaged the intestine. The researchers observed a near-complete depletion of Bacteroidota, one of the dominant bacterial phyla in a healthy mammalian gut, alongside a striking expansion of Escherichia-Shigella and Klebsiella, groups that include opportunistic pathogens and are often associated with antibiotic-driven blooms. This pattern of losing beneficial, fiber-fermenting taxa while resistant and potentially pathogenic organisms fill the vacuum is a classic signature of antibiotic dysbiosis, and the study shows it can be exceptionally severe after H. pylori treatment.

Recovery on its own proved slow and incomplete. Four weeks after the end of therapy, mice left to recover spontaneously had not returned to their pre-treatment microbial state. This finding carries weight for the millions of people who undergo eradication therapy each year, since it suggests that the ecological cost of treatment may linger well beyond the course of antibiotics, potentially contributing to post-treatment digestive complaints and, in theory, longer-term metabolic and immune consequences.

Probiotic supplementation changed that trajectory substantially. Mice receiving E. faecium R0026 and B. subtilis R0179 showed significantly accelerated restoration of the gastrointestinal microbiome, with effects that preferentially shaped the intestinal community. In the stomach, the probiotics helped replenish depleted dominant taxa, including Pseudomonas, members of the Muribaculaceae family, and Ligilactobacillus, a lactic acid-producing genus. In the gut, the intervention enriched Bacteroidota and boosted short-chain fatty acid producers such as Lachnospiraceae_FCS020_group and Ligilactobacillus. Short-chain fatty acids are microbial metabolites with wide-ranging effects, from nourishing the cells lining the colon to regulating immune responses and maintaining the integrity of the intestinal barrier.

Perhaps the most novel contribution of the study lies in its analysis of shared microbial taxa between the stomach and the intestine. By sequencing paired samples, the researchers could identify amplicon sequence variants, or ASVs, present in both compartments, a measure of trans-compartment connectivity. Eradication therapy severely disrupted this shared pool, effectively severing the microbial links between the two organs. Probiotic administration restored this connectivity, and the rebuilt network proved more stable than before. The authors interpret this as evidence that probiotics do not merely patch one compartment locally but actively orchestrate a synergistic recovery across the gastrointestinal tract, re-establishing the ecological dialogue between stomach and gut.

The functional predictions added another layer of support. Microbial communities in the probiotic-treated mice showed enrichment of predicted pathways related to short-chain fatty acid metabolism and immune modulation, and these shifts coincided with improved intestinal barrier integrity. In other words, the microbial recovery was not just a matter of which species were present, but of what the restored community appeared to be doing, with the predicted functions aligning with a healthier, more resilient gut environment. The researchers also note that the work was supported by funding from the National Natural Science Foundation of China and provincial research programs in Jiangxi Province.

As with all preclinical work, important caveats apply. The findings come from mice, and the strains, doses, and timing used in the study cannot be directly translated into clinical recommendations without human trials. The probiotic strains tested are specific formulations, and probiotic effects are notoriously strain- and context-dependent, meaning that results cannot be generalized to all products on pharmacy shelves. Nevertheless, the study provides what the authors describe as compelling preclinical evidence for probiotics as an adjunctive strategy to counter eradication-induced dysbiosis. Given that H. pylori infects roughly half the world’s population and eradication campaigns are expanding in many countries, strategies that soften the ecological collateral damage of treatment could have broad public health relevance, and this paired, network-based approach offers a template for testing them rigorously.

Subject of Research: Probiotic modulation of gastric and intestinal microbiota recovery after Helicobacter pylori eradication therapy

Article Title: Probiotics modulate the interactions between gastric and intestinal microbiota after Helicobacter pylori eradication

Article References: Huang, C., Peng, C., Ouyang, Y., Xu, X., Lu, N., & He, C. (2026). Probiotics modulate the interactions between gastric and intestinal microbiota after Helicobacter pylori eradication. Gut Pathogens. https://doi.org/10.1186/s13099-026-00889-3

Image Credits: AI Generated

DOI: 10.1186/s13099-026-00889-3

Keywords: Helicobacter pylori, probiotics, microbiota, dysbiosis, triple therapy, gastric microbiome, gut microbiome, short-chain fatty acids, 16S rRNA sequencing, Bacteroidota, intestinal barrier, microbial ecology