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. 2025 Feb 5;25(1):54.
doi: 10.1186/s12876-025-03631-6.

Helicobacter pylori CagA+ strains modulate colorectal pathology by regulating intestinal flora

Shasha Cui  1 , Xinqiang Liu  2 , Fengxia Han  1 , Lu Zhang  2 , Jingjing Bu  1 , Sainan Wu  1 , Jiafen Wang  3
Affiliations

Helicobacter pylori CagA+ strains modulate colorectal pathology by regulating intestinal flora

Shasha Cui et al. BMC Gastroenterol. .

Abstract

Aim: This article aims to investigate the role of Helicobacter Pylori (HP) CagA+ strains affected colorectal lesion via gut microbiota.

Method: 6-week C57BL/6J mice were divided into: (a) HP CagA+ group undergoing HP CagA+ strains administration by gavage at 0.2 mL for 10 days; (b) HP CagA- group undergoing HP CagA- strains administration by gavage at 0.2 mL for 10 days; (c) control group intragastrically given 0.2 mL of brian heart infusion (BHI) medium for 10 days. Gastric mucosa was collected for Giemsa staining, and colorectal mucosa was for hematoxylin and eosin (H&E) staining, 16 S ribosomal RNA (rRNA) sequencing and immunohistochemistry for Major Histocompatibility Complex (MHC). Colon tissues and serum from caudal vein was collected for quantification of interleukin (IL)-6, IL-8, IL10 and tumor necrosis factor (TNF-α).

Results: Mice with HP CagA+ infection developed loss of some resident cells and inflammation infiltration in colorectal mucosa, and increased Giemsa-positive cells in gastric tissue. Also, MHC II-positive cells were increased in colorectal tissue in HP CagA+ strains infection. HP CagA+ infection cause increase of TNF-α, IL-6, IL-8 and IL-10 in the serum. Meanwhile, HP CagA+ stainis evoked gut microbiota dysbiosis which was characterized by altered microbiome distribution, reduction in Front-to-Back (F/B ratio), decreased α-diversity metric (Chao1 and Shannon). In β-diversity, gut microbiota in control and HP CagA+ groups showed the significant distance based on UniFrac distance. Cag group was enriched a higher abundance of Staphylococcus and Corynebacterium, while control subjects were enriched in Marinifilaceae and Odoribacter.

Conclusion: HP CagA+ strains are capable of causing gut microbiota dysbiosis to develop destruction of intestinal barrier, and it may affect the development of colorectal cancer by increasing colonization of Staphylococcus and Corynebacterium.

Keywords: CagA+; Colorectal lesion; Gut microbiota; Helicobacter pylori.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: Animal experiments have been approved by the Medical Committee of Binzhou People’s Hospital ((2020) No. 249). Human studies at Binzhou People’s Hospital are endorsed by the Medical Committee of Binzhou People’s Hospital ((2020) No. 249), implementing Helsinki Declaration principles. Written informed consent is produced from patients. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Role of HP CagA+ strains in serum cytokines. A-D, HP-CagA+ strains increased TNF-α (A), IL-6 (B), IL-8 (C) and IL-10 (D) in the serum and colon tissues. Control group (n = 10), mice administrated with BHI medium by gavage; HP CagA+ group (n = 10), mice infected by HP CagA+ strains via intragastric administration; HP CagA- group (n = 10), mice infected by HP CagA- strains via intragastric administration. Data represent means ± SD, **p < 0.01
Fig. 2
Fig. 2
Role of HP CagA+ strains in gastric and colorectal tissues. A, HP CagA+ infection induced histopathological lesion in gastric (stained by Giemsa) and colorectal tissue (stained by H&E staining). B, HP CagA+ infection increased MHC II expression in colorectal tissue. Control group (n = 10), mice administrated with BHI medium by gavage; HP CagA+ group (n = 10), mice infected by HP CagA+ strains via intragastric administration; HP CagA- group (n = 10), mice infected by HP CagA- strains via intragastric administration. Data represent means ± SD, **p < 0.01
Fig. 3
Fig. 3
Role of HP CagA+ strains in α-diversity in gut microbiota. A-D, HP CaA+ strains altered gut microbiota composition at the phylum (A), class (B), family (C) and genus (D). E&F, HP CagA+ strains decreased α-diversity indexes including Shannon (E) and Chao1 (F). Control group (n = 10), mice administrated with BHI medium by gavage; HP CagA+ group (n = 10), mice infected by HP CagA+ strains via intragastric administration
Fig. 4
Fig. 4
Role of HP CagA+ infection in β-diversity in gut microbiota. A, Unifrac distance. B, PCoA analysis. C,Adnosis analysis. Control group (n = 10), mice administrated with BHI medium by gavage; HP CagA+ group (n = 10), mice infected by HP CagA+ strains via intragastric administration
Fig. 5
Fig. 5
Identification and functional analysis for signature gut microbiota. A-F, MetaStat Analysis. G, Histogram of LDA Score distribution. The difference of species abundance between two groups. H, Results of the functional annotations in the Control group and Cag group based on the KO database
See this image and copyright information in PMC

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