Cascading effects of combining acid suppressants with anti-tuberculosis therapy on the microbiome and clinical outcomes: narrative review
Combining acid suppressants (especially PPIs) with anti-tuberculosis drugs exacerbates gut dysbiosis through a dual independent mechanism, with a biologically plausible — but clinically unquantified — impact on tuberculosis treatment efficacy.
| Population | Patients with active tuberculosis on standard anti-tuberculosis regimens |
|---|---|
| Intervention | Co-administration of acid suppressants (PPIs or H2 receptor antagonists) alongside anti-tuberculosis therapy |
| Comparator | Anti-tuberculosis therapy without acid suppressants |
| Outcome | Gut microbiome alpha diversity during ATD; Abundance of SCFA producers (Faecalibacterium, Roseburia, Ruminococcus); PPI-induced oral-to-gut translocation (Streptococcus, Rothia); Proliferation of opportunistic pathogens (Bacteroides fragilis, Enterococcus); Clinical anti-tuberculosis treatment efficacy (cure, sputum conversion) under dual exposure; Pulmonary immune function mediated by the gut–lung axis; Incidence of gastrointestinal reactions during ATD |
Summary of findings
| Outcome | Effect | 95% CI | Certainty | Clinical relevance | Notes |
|---|---|---|---|---|---|
| Gut microbiome alpha diversity during ATD | consistent decrease reported across multiple studies; in the pooled effect size or 95% CI available | — | Low | — | |
| Abundance of SCFA producers (Faecalibacterium, Roseburia, Ruminococcus) | directional decrease reported; in the pooled OR/RR or 95% CI available | — | Low | — | |
| PPI-induced oral-to-gut translocation (Streptococcus, Rothia) | directional enrichment reported in observational/metagenomic studies; in the pooled effect size or 95% CI available | — | Low | — | |
| Proliferation of opportunistic pathogens (Bacteroides fragilis, Enterococcus) | directional increase reported; in the pooled effect size or 95% CI available | — | Low | — | |
| Clinical anti-tuberculosis treatment efficacy (cure, sputum conversion) under dual exposure | no direct clinical data reported; causal inference only | — | Very low | — | |
| Pulmonary immune function mediated by the gut–lung axis | mechanistic inference from animal and indirect human data; in the direct effect size available | — | Very low | — | |
| Incidence of gastrointestinal reactions during ATD | 71.8% incidence reported (single cited clinical dataset); in the 95% CI or comparative effect size available | — | Low | — | 1 studies |
Context
Gastrointestinal adverse reactions occur in up to 71.8% of patients on standard anti-tuberculosis therapy (2HRZE/4HR), routinely prompting co-prescription of acid suppressants. Both drug classes disrupt the gut microbiome through distinct and potentially additive mechanisms. Direct evidence linking combined-regimen-induced dysbiosis to tuberculosis treatment outcomes is lacking.
What the study showed
Standard anti-tuberculosis regimens consistently reduce gut microbiome alpha diversity, deplete SCFA producers (Ruminococcus, Faecalibacterium, Roseburia), and increase opportunistic pathogens (Bacteroides fragilis, Enterococcus). PPIs add dysbiosis via a distinct mechanism — elevated gastric pH enabling oral-to-gut translocation of Streptococcus and Rothia — with additional depletion of Faecalibacterium and Roseburia. The review provides no original clinical data comparing cure rates, sputum conversion, or mortality between patients who did or did not use acid suppressants.
How it was done
Narrative (non-systematic) review synthesising observational studies, clinical trials, animal studies, and metagenomic analyses on the effects of anti-tuberculosis drugs and acid suppressants on the gut microbiome and the gut–lung axis in tuberculosis. No PRISMA-compliant systematic search, standardised data extraction, or formal risk-of-bias assessment was reported.
Effect magnitude
Not applicable: the review reports no consolidated effect size for any primary clinical outcome. Supporting data cite a 71.8% incidence of gastrointestinal reactions during ATD and persistent microbial diversity reduction, but without a unified 95% CI or effect size for the PPI + ATD combination.
Risk of bias
Narrative review with no registered protocol, no systematic search, and no risk-of-bias assessment (AMSTAR-2 formally inapplicable; absence of PRISMA criteria is a critical limitation). Causality between combined dysbiosis and tuberculosis clinical outcomes is inferred, not demonstrated. Heterogeneity of cited studies (animal models, human studies across diverse settings) precludes quantitative synthesis.
What this study does NOT prove
This study does not prove that combining PPIs with anti-tuberculosis drugs worsens clinical tuberculosis outcomes in humans; the entire causal chain of dysbiosis → immunity → therapeutic efficacy remains inferred from indirect and mechanistic evidence. Conclusions cannot be generalised to populations with comorbidities (HIV, diabetes, malnutrition) without population-specific data.
In clinical practice
Clinicians should weigh the risk–benefit profile when co-prescribing PPIs in tuberculosis patients: there is a biological basis for concern about additive dysbiosis, but no direct clinical evidence of worsened outcomes. H2 receptor antagonists show less documented microbiome impact and may be preferred when acid suppression is necessary. Microbiome support strategies (probiotics, dietary interventions) warrant prospective evaluation in this population.
Limitations
Narrative review with no registered protocol, no systematic search, and no risk-of-bias assessment (AMSTAR-2 formally inapplicable; absence of PRISMA criteria is a critical limitation). Causality between combined dysbiosis and tuberculosis clinical outcomes is inferred, not demonstrated. Heterogeneity of cited studies (animal models, human studies across diverse settings) precludes quantitative synthesis.
What is still missing
Prospective clinical studies — ideally RCTs — comparing sputum conversion, cure, and relapse outcomes between tuberculosis patients receiving or not receiving acid suppressants, with longitudinal metagenomic microbiome analysis as an intermediate endpoint.
Technical appendix
Version history
- 1.0 · 2026-10-16 — Auto-generated under Evidence Standard v1.0