Shifts in the Human Gut Microbiota Structure Caused by Quadruple Helicobacter pylori Eradication Therapy

Abstract

The human gut microbiome plays an important role both in health and disease. Use of antibiotics can alter gut microbiota composition, which can lead to various deleterious events. Here we report a whole genome sequencing metagenomic/genomic study of the intestinal microbiota changes caused by Helicobacter pylori (HP) eradication therapy. Using approaches for metagenomic data analysis we revealed a statistically significant decrease in alpha-diversity and relative abundance of Bifidobacterium adolescentis due to HP eradication therapy, while the relative abundance of Enterococcus faecium increased. We have detected changes in general metagenome resistome profiles as well: after HP eradication therapy, the ermB, CFX group, and tetQ genes were overrepresented, while tetO and tetW genes were underrepresented. We have confirmed these results with genome-resolved metagenomic approaches. MAG (metagenome-assembled genomes) abundance profiles have changed dramatically after HP eradication therapy. Focusing on ermB gene conferring resistance to macrolides, which were included in the HP eradication therapy scheme, we have shown a connection between antibiotic resistance genes (ARGs) and some overrepresented MAGs. Moreover, some E. faecium strains isolated from stool samples obtained after HP eradication have manifested greater antibiotic resistance in vitro in comparison to other isolates, as well as the higher number of ARGs conferring resistance to macrolides and tetracyclines.

Long‐term changes in the gut microbiota after 14‐day bismuth quadruple therapy in penicillin‐allergic children

“…We searched PubMed using the terms “Helicobacter”, “eradication” and “microbiota” for papers published from January 1, 2000, to March 12, 2020, in English. Sixteen studies using high‐throughput sequencing to assess alterations in the gut microbiota before and after H pylori eradication are summarized in Table 17‐32 . 10 publications focus on the impact of standard triple therapy and 5 studies address the long‐term (at least one year) effect after treatment.…”

Helicobacter pylori infection and eradication: Exploring their impacts on the gastrointestinal microbiota

“…Similarly, other researchers recorded alpha diversity at weeks 0, 2, 8, and 48 reporting that the value was recovered at week 8 as well 53 . In accordance with these reports, most studies gathering follow‐up information within 2 months showed a decreased alpha diversity, whereas studies gaining information thereafter frequently reported no significant differences with baseline 9,50,51,53‐57 . Nevertheless, one study reported that both Sobs index and Chao index kept decreasing from week 0 to week 6 and week 26, though statistical significance was not reached 34 .…”

Using Probiotics as Supplementation for Helicobacter pylori Antibiotic Therapy

“…Another challenge for the antibiotic therapy of H. pylori are side effects. These may occur in some patients, the combination of two antibiotics causes more damage to the host gastrointestinal microbiota and leads to the imbalanced microbial population associated with the proliferation of gastrointestinal pathogens [56][57][58]. Additionally, PPI induction decreases in gastric acid secretion may increase the mobility of these pathogens, enable them to circulate in the gastrointestinal tract [59,60].…”

“…H. pylori infection alters both the gastric and intestinal microflora [110]. At the same time, the bactericidal effect of antibiotic use and the pH change caused by PPI can lead to more severe disorders [56][57][58][59][60]. Clinical studies have confirmed that H. pylori infection reduces the diversity of the stomach microbiota in children and adults, and this microbiota may not be restored after eradicating the pathogen [15,111].…”

“…Lactobacillus spp.in the stomach dramatically decreased after penicillin was administered to a mouse model [15]. In an infected population treated with quadruple therapy, the alpha diversity and B. adolescentis abundance in the gut microbiota was significantly decreased, and some E. faecalis strains acquired even greater antibiotic resistance [57]. Intake of probiotics may produce positive effects in terms of protecting and recovering the gastrointestinal microbiota [112].…”