H. pylori eradication therapy may alter human gut virome

Helicobacter pylori eradication therapy not only resulted in transient alteration of gut microbiota, but also significantly altered the gut virome, researchers from the University of Hong Kong (HKU) have found.

H. pylori infection is the major cause of gastric cancer and peptic ulcer disease, with a markedly high global prevalence rate of 58.2 percent in 1980–1990. A recent meta-analysis (n=2,979,179) showed a steadily declining global prevalence rate over the last 40 years, reaching 43.1 percent in 2011–2022. [Lancet Gastroenterol Hepatol 2023;doi:10.1016/S2468-1253(23)00070-5]

“The decline in global prevalence is attributed to successful H. pylori eradication in infected patients and reduction in the acquisition of new infections, including reinfection,” noted the researchers. However, previous findings suggested that gut microbiota was altered following H. pylori eradication therapy. While most researchers focused on the changes in gut microbiota, the HKU researchers sought to examine changes in the gut virome in H. pylori–infected patients (n=44) at 6 weeks and 6 months after eradication therapy. [Nat Commun 2023;14:2196]

Twenty-one treatment-naïve patients were given clarithromycin-based triple therapy, while 23 patients with refractory H. pylori infection were given levofloxacin- or bismuth-based quadruple therapy or other combinations, depending on their previous treatment regimens.

Using metagenomic sequencing, the researchers identified 3,581 different viral species in the patients’ faecal samples. The viral species found in >50 percent, 20–50 percent and <20 percent of the samples were defined as core viruses (n=12), common viruses (n=66) and unique viruses (n=3,503), respectively.

Core virus richness was found to be diminished 6 weeks after treatment (false discovery rate [FDR], 0.002) and gradually restored at 6 months (FDR, 0.382), while common and unique viruses significantly decreased at both 6 weeks (FDR, 0.001 and 5.44 x 10^-5, respectively) and 6 months (FDR, 0.003 and 1.34 x 10^-4, respectively) after H. pylori eradication.

Notably, the gut virome community was reshaped after H. pylori eradication therapy, with total virus richness significantly reduced at both 6 weeks (FDR, 4.74 x 10^-05) and 6 months (FDR, 1.94 x 10^-04) vs baseline. In addition, the baseline virome community was distinct from that at 6 months after H. pylori eradication (PERMANOVA; FDR, 0.012).

“Unlike changes in gut bacteria composition, which can typically be restored at 6 months, the contraction in virus community persisted for more than 6 months, indicating that the gut microbiota community was more resilient and easier to recover vs the gut virome community after H. pylori eradication therapy,” highlighted lead researcher, Professor Wai-Keung Leung from the Department of Medicine, HKU.

In addition, treatment-refractory patients showed a significantly lower virome diversity vs treatment-naïve patients at baseline, 6 weeks and 6 months (all p<0.05). “The findings indicated that multiple courses of eradication therapies could have a more profound effect on the gut virome,” pointed out the researchers.

The impact of H. pylori eradication treatment in reshaping the gut virome, as shown in the study, could negatively affect individuals’ health as gut virome may contribute to development of diseases such as diabetes and irritable bowel syndrome. [FEMS Microbiol Rev 2022;doi:10.1093/femsre/fuac027]