Metaproteomic assessment of gut microbial and host functional perturbations in Helicobacter pylori-infected patients subjected to an antimicrobial protocol

ABSTRACT

The impact of therapeutic interventions on the human gut microbiota (GM) is a clinical issue of paramount interest given the strong interconnection between microbial dynamics and human health. Orally administered antibiotics are known to reduce GM biomass and modify GM taxonomic profile. However, the impact of antimicrobial therapies on GM functions and biochemical pathways has scarcely been studied. Here, we characterized the fecal metaproteome of 10 Helicobacter pylori-infected patients before (T0) and after 10 days (T1) of a successful quadruple therapy (bismuth, tetracycline, metronidazole, and rabeprazole) and 30 days after therapy cessation (T2), to investigate how GM and host functions change during the eradication and healing processes. At T1, the abundance ratio between microbial and host proteins was reversed compared with that at T0 and T2. Several pathobionts (including Klebsiella, Proteus, Enterococcus, Muribaculum, and Enterocloster) were increased at T1. Therapy reshaped the relative contributions of the functions required to produce acetate, propionate, and butyrate. Proteins related to the uptake and processing of complex glycans were increased. Microbial cross-feeding with sialic acid, fucose, and rhamnose was enhanced, whereas hydrogen sulfide production was reduced. Finally, microbial proteins involved in antibiotic resistance and inflammation were more abundant after therapy. Moreover, a reduction in host proteins with known roles in inflammation and H. pylori-mediated carcinogenesis was observed. In conclusion, our results support the use of metaproteomics to monitor drug-induced remodeling of GM and host functions, opening the way for investigating new antimicrobial therapies aimed at preserving gut environmental homeostasis.

KEYWORDS:

• Antibiotics
• fecal sample
• gut microbiota
• human metaproteome
• infection
• microbial functions

Acknowledgments

The Laboratory of Proteomics-UMG at the University of Catanzaro (Italy) is acknowledged for LC-MS/MS analyses.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The mass spectrometry proteomics data (including peptide identification, quantification and annotation tables) have been deposited to the ProteomeXchange Consortium via the PRIDE⁷⁹ partner repository with the dataset identifier PXD042946.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/19490976.2023.2291170

Additional information

Funding

This work was supported by the Italian MIUR (Project PON04a2_00557 to SU) and by Fondazione di Sardegna/University of Sassari (Bando Fondazione di Sardegna 2018-2020 e 2021/Progetti di Ricerca di Base Dipartimentali D.R. 2397/2021 to SU, Fondo di Ateneo per la Ricerca 2020 to SU and AT).