Abstract
Abstract
Purpose
Gut resilience and systemic homeostasis are interrelated dynamic functions. A gut that fails to regulate intestinal barrier integrity, metabolite production, and immune regulation will lead to systemic pathogenic invasion and susceptibility to infections. Gut resilience withstands stressors that can induce gut failure, and even when disturbances occur, it quickly restores its composition and functions. There is a paucity of data on the microbiome of people living in low- and middle-income settings. We therefore assessed the local and systemic conditions of gut resilience following neomycin treatment in individuals with intestinal soil-transmitted helminth infections.
Methods
A randomised, placebo-controlled, participant-blinded study was conducted in adults up to 40 years with known soil-transmitted helminth infections (STH) living in Lambaréné, Gabon. Participants were randomly assigned to the intervention or placebo groups. The intervention group received neomycin 2000 mg per os (p.o) three times daily for 10 days and fluconazole 150 mg p.o once weekly for two weeks. On day 90, all study participants were treated with 400 mg of albendazole for three days. Outcome measures included egg counts of
Ascaris lumbricoides
,
Necator americanus
and
Trichuris trichiura
, a dual marker of gut barrier permeability and metabolite production (FABP2), incidence of adverse events, and assessment of pathogen proliferation.
Results
Thirty-eight participants were enrolled and followed up for 180 days. At the gut level, the intestinal STH egg counts decreased on day 7 after neomycin administration. From day 14 onward, intestinal STH egg counts began to increase, reaching the initial counts by day 90. There was no difference in FABP2 marker concentration between the two groups. Adverse events occurred more frequently in the intervention group, most commonly side effects of neomycin and fluconazole. There was no pathogen proliferation.
Conclusion
Broad-spectrum antibiotic-induced changes in laying of STH helminth eggs in STH-infected adults, which occurred at the peak of the drug concentration observed in the blood, corresponding to a high availability in the gut. These changes support that the antibiotic-induced changes were transient and did not induce occurrence of clinical peripheral changes. The local resilience of the gut translated into peripheral-maintained homeostasis.
Trial registration
The study was registered at the Pan African Clinical Trial Registry (https//pactr.samrc.ac.za/) database with identification numberPACTR201707002361207.