Altered Gut Microbiota and Short-Chain Fatty Acids After Vonoprazan-Amoxicillin Dual Therapy for Helicobacter pylori Eradication

Yi Hu, Xin Xu, Yao-Bin Ouyang, Cong He, Nian-Shuang Li, Chuan Xie, Chao Peng, Zhen-Hua Zhu, Xu Shu, Yong Xie, Nong-Hua Lu, Yin Zhu, Yi Hu, Xin Xu, Yao-Bin Ouyang, Cong He, Nian-Shuang Li, Chuan Xie, Chao Peng, Zhen-Hua Zhu, Xu Shu, Yong Xie, Nong-Hua Lu, Yin Zhu

Abstract

The combination of vonoprazan (VPZ) and amoxicillin (VA therapy) has been shown to achieve acceptable eradication rates for Helicobacter pylori (H. pylori). Herein, our aim was to explore the short-term effect of VA therapy on the gut microbiota and short-chain fatty acids (SCFAs) using human fecal samples. A total of 119 H. pylori-positive patients were randomized into low- or high-dose VA therapy (i.e., amoxicillin 1 g b.i.d. or t.i.d. and VPZ 20 mg b.i.d.) for 7 or 10 days. Thirteen H. pylori-negative patients served as controls. Fecal samples were collected from H. pylori-positive and H. pylori-negative patients. The gut microbiota and SCFAs were analyzed using 16S rRNA gene sequencing and gas chromatography-mass spectrometry, respectively. The gut microbiota in H. pylori-positive patients exhibited increased richness, diversity, and better evenness than matched patients. Fifty-three patients studied before and after H. pylori eradication were divided into low (L-VA) and high (H-VA) amoxicillin dose groups. The diversity and composition of the gut microbiota among L-VA patients exhibited no differences at the three time points. However, among H-VA patients, diversity was decreased, and the microbial composition was altered immediately after H-VA eradication but was restored by the confirmation time point. The decreased abundance of Anaerostipes, Dialister, and Lachnospira induced by H-VA was associated with altered SCFA levels. VA dual therapy for H. pylori eradication has minimal negative effects on gut microbiota and SCFAs.

Keywords: Helicobacter pylori; amoxicillin; eradication; gut microbiota; short-chain fatty acids; vonoprazan.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2022 Hu, Xu, Ouyang, He, Li, Xie, Peng, Zhu, Shu, Xie, Lu and Zhu.

Figures

Figure 1
Figure 1
The flowchart of this study and diversity of the gut microbiota between H. pylori-positive patients and normal controls. (A) Overview of the study design. Bacterial alpha diversity estimated by Chao1 (B), Shannon (C), and Pielou indices (D) between H. pylori-positive patients and normal controls. (E) Bacterial beta diversity estimated by PCoA between H. pylori-positive patients and normal controls. L-VA: dual therapy consisting of a low dose of amoxicillin (1000 mg b.i.d.) and VPZ (20 mg b.i.d.); H-VA: dual therapy consisting of a high dose of amoxicillin (1000 mg t.i.d.) and VPZ (20 mg b.i.d.); SCFAs, short-chain fatty acids; Hp, H. pylori-positive; Control, H. pylori-negative; PCoA, principal coordinate analysis. *P < 0.05, **P < 0.01.
Figure 2
Figure 2
The composition and predicted functional differences between H. pylori-positive patients and normal controls. (A) The composition of the gut microbiota between H. pylori-positive patients and normal controls at the phylum level (the abundance of the top 10 is shown). (B) Differences in specific bacterial taxa between H. pylori-positive and normal controls by LEfSe. (C) Significant signaling pathways associated with H.pylori infection according to KEGG pathway analysis. Ecological co-occurrence network between H. pylori-positive (D), and normal controls (E) Hp: H.pylori-positive; Control: H. pylori-negative.
Figure 3
Figure 3
Analysis of SCFAs in H. pylori-positive patients and normal controls. (A) Heatmap of SCFA differences across different samples in H. pylori-positive and normal control groups. The quantification of total SCFAs (B), acetic acid (C), propionic acid (D), butyric acid (E), isobutyric acid (F), isovaleric acid (G), valeric acid (H), and hexanoic acid (I) in the H. pylori-positive patients and normal control groups. Hp: H. pylori-positive; Control: H. pylori-negative.
Figure 4
Figure 4
The diversity of the gut microbiota between the L-VA and H-VA therapy groups. Bacterial alpha diversity estimated by Chao1 (A), Shannon (B), and Pielou indices (C) at the three time points of L-VA therapy. The Chao1 (D), Shannon (E), and Pielou indices (F) at the three time points of H-VA therapy. Bacterial beta diversity estimated by PCoA at three time points of L-VA (G) and H-VA (H) therapy. L-VA: dual therapy consisting of a low dose of amoxicillin (1000 mg b.i.d.) and VPZ (20 mg b.i.d.); H-VA: dual therapy consisting of a high dose of amoxicillin (1000 mg t.i.d.) and VPZ (20 mg b.i.d.); L-1: the time point before eradication in the L-VA group; L-2: the time point after eradication in the L-VA group; L-3: the time point of confirmation in the L-VA group; H-1: the time point before eradication in the H-VA group; H-2: the time point after eradication in the H-VA group; H-3: the time point of confirmation in the H-VA group; * P<0.05.
Figure 5
Figure 5
Composition differences at the three time points in L-VA and H-VA therapy. The composition of the gut microbiota between L-VA (A) and H-VA (B) therapy at the phylum level (the abundance of Top 10 are shown). Differences in specific bacterial taxa when comparing L-1 and L-2 (C), L-2 and L-3 (D), H-1 and H-2 (E), and H-2 and H-3 (F) by LEfSe. L-1: the time point before eradication in the L-VA group; L-2: the time point after eradication in the L-VA group; L-3: the time point of confirmation in the L-VA group; H-1: the time point before eradication in the H-VA group; H-2: the time point after eradication in the H-VA group; H-3: the time point of confirmation in the H-VA group.
Figure 6
Figure 6
SCFA analysis of L-VA therapy. Heatmap of SCFA differences across different samples at the three time points of L-VA therapy (A for L-1 and L-2, B for L-2 and L-3, C for L-1 and L-3). The quantification of total SCFAs (D) and acetic acid (E) at the three time points of L-VA therapy. Red represents a positive association, and blue represents a negative association. L-1: the time point before eradication in the L-VA group; L-2: the time point after eradication in the L-VA group; L-3: the time point of confirmation in the L-VA group; * P<0.05.
Figure 7
Figure 7
SCFA analysis of H-VA therapy. Heatmap of SCFA differences across different samples at the three time points of H-VA therapy (A for H-1 and H-2, B for H-2 and H-3, C for H-1 and H-3), red represents a positive association, and blue represents a negative association. The quantification of total SCFAs (D), acetic acid (E), propionic acid (F), and valeric acid (G) at the three time points of H-VA therapy. (H) Integrated analysis of SCFA alterations associated with gut microbiota among the H-VA group, blue represents a positive association, and red represents a negative association. H-1: the time point before eradication in the H-VA group; H-2: the time point after eradication in the H-VA group; H-3: the time point of confirmation in the H-VA group; * P<0.05.

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