The Effect of Probiotics Supplementation on Gut Microbiota After Helicobacter pylori Eradication: A Multicenter Randomized Controlled Trial

Abstract

Introduction Helicobacter pylori eradication therapy may lead to the perturbation of gut microbiota. We aim to investigate the impact of probiotics on eradication rate and gut microbiota during eradication therapy. Methods A total of 162 patients receiving bismuth quadruple therapy were enrolled and randomly assigned to groups given probiotics ( n = 83) or placebo ( n = 79) for 4 weeks. Fecal samples were collected before treatment and 2, 4, 6, and 8 weeks after eradication therapy. Gut microbiota was analyzed by 16S rRNA high-throughput sequencing. Results The eradication rates in the placebo and probiotics group were 82.43% and 87.01%, respectively ( P > 0.05). Compared with baseline, alpha and beta diversity was significantly altered 2 weeks after eradication in both groups, which was restored at week 8. There were no significant differences in diversity between the two groups. H. pylori eradication therapy resulted in enrichment of some detrimental bacteria taxa such as Shigella , Klebsiella , and Streptococcus , while probiotics supplementation could rapidly restore these taxa levels after eradication and increase the taxa of Bacillus and Lactobacillales. Functional analysis revealed that lipopolysaccharide biosynthesis and polymyxin resistance pathways were significantly enriched after eradication, while probiotics supplementation mainly enriched the cofactors and vitamins metabolism pathways. Increased relative abundances of Roseburia and Dialister were associated with the positive eradication outcome. Conclusions Probiotics supplementation might help to construct a beneficial profile of gut microbiota after eradication therapy. Specific bacteria taxa are associated with H. pylori eradication outcome. These findings may be of value in rational use of probiotics during H. pylori eradication. Trial Registration Chinese Clinical Trial Registry, ChiCTR1900022116. Electronic supplementary material The online version of this article (10.1007/s40121-020-00372-9) contains supplementary material, which is available to authorized users.

Gut Microbiota: The Missing Link Between Helicobacter pylori Infection and Metabolic Disorders?

“…Quadruple therapy with bismuth during 10 or 14 days also led to decreased bacterial diversity but not all the studies found a total recovery of bacterial diversity evaluated from 6 weeks to 1 year posttreatment (16,36,38,44). By contrast, concomitant therapy of three antibiotics (amoxicillin, clarithromycin, metronidazole) without bismuth for 14 days decreased bacterial diversity, but it was fully (35) or partly restored (36) at 2 months or 1 year posttreatment, respectively.…”

“…There is growing evidence that antibiotic-based therapies for H. pylori eradication promote alterations in the gut microbiota (10,11,16,17,24,(35)(36)(37)(38)(39)(40)(41)(42)(43)(44), but different antibiotic combinations can exert differential effects on microbial community (166) (Table 2). In addition, proton pump inhibitors (PPI) which is usually administered together antibiotics for H. pylori eradication also contributes to bacterial shifts in the intestine (167).…”

“…Many studies have reported changes in specific bacterial taxa, but most of these findings remains controversial (10,11,16,17,24,(35)(36)(37)(38)(39)(40)(41)(42)(43)(44). While some studies have observed a decrease in Firmicutes, Bacteroidetes, and an increase in Proteobacteria 2 weeks after triple (41), quadruple (17,36,38,44) or concomitant (35) therapies, other studies have shown an increase in Bacteroidetes (11) and a decrease in Proteobacteria (11, 24) after triple therapy. The phylum Actinobacteria (24,40,43,44) and members belonging to this phylum as Bifidobacteriales (43), Bifidobacterium (39), Bifidobacteria (40), and Bifidobacterium adolescentis (37) also remained decreased at 1 or 2 weeks post-treatment regardless of the therapy used.…”

“…On the contrary, the relative abundance of several putative detrimental bacteria which can release harmful factors for host's health, such as Escherichia, Proteus, Morganella (35,44), Serratia (44), Klebsiella (17,35,38,44) and Streptococcus (38,44) augmented upon antibiotic administration (quadruple or concomitant therapy) (Table 2).…”

“…Therapies for H. pylori eradication are based on the use of different antibiotic combinations (27)(28)(29) which are well known to have profound effects on the composition and diversity of the gut microbiota (30) and might also be related to adiposity and insulin resistance (31)(32)(33)(34). Although an increasing number of studies have emerged analyzing the effects of the various antibiotic eradication therapies for H. pylori eradication on the composition of the gut microbiota (10,11,16,17,24,(35)(36)(37)(38)(39)(40)(41)(42)(43)(44), few of them have related these changes with patients' metabolic traits (10,(22)(23)(24). Within this context, our group has recently focused on analyzing how gut microbial changes promoted by H. pylori and its treatment can relate to metabolic traits.…”