Gut Liver. 2024;18(4):654-666.

The Possible Preventative Role of Lactate- and Butyrate-Producing Bacteria in Colorectal Carcinogenesis.

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제1저자 송진희 · 교신저자 김나영

PMID 38030382 PMC11249946 DOI 10.5009/gnl230385 IF 4.1 소화기내과

소속 (4)

Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Viral Immunology Laboratory, Institut Pasteur Korea, Seongnam, Korea.
Department of Biological Sciences and Institute of Microbiology, Seoul National University, Seoul, Korea.

Abstract

BACKGROUND/AIMS : The gut microbiome has emerged as a key player that mechanistically links various risk factors to colorectal cancer (CRC) etiology. However, the role of the gut microbiome in CRC pathogenesis remains unclear. This study aimed to characterize the gut microbiota in healthy controls (HCs) and patients with colorectal adenoma (AD) and CRC in subgroups based on sex and age.

METHODS : Study participants who visited the hospital for surveillance of CRC or gastrointestinal symptoms were prospectively enrolled, and the gut microbiome was analyzed based on fecal samples.

RESULTS : In terms of HC-AD-CRC sequence, commensal bacteria, including lactate-producing (Streptococcus salivarius) and butyrate-producing (Faecalibacterium prausnitzii, Anaerostipes hadrus, and Eubacterium hallii) bacteria, were more abundant in the HC group than in the AD and CRC groups. In the sex comparison, the female HC group had more lactate-producing bacteria (Bifidobacterium adolescentis, Bifidobacterium catenulatum, and Lactobacillus ruminis) than the male HC group. In age comparison, younger subjects had more butyrate-producing bacteria (Agathobaculum butyriciproducens and Blautia faecis) than the older subjects in the HC group. Interestingly, lactate-producing bacteria (B. catenulatum) were more abundant in females than males among younger HC group subjects. However, these sex- and age-dependent differences were not observed in the AD and CRC groups.

CONCLUSIONS : The gut microbiome, specifically lactate- and butyrate-producing bacteria, which were found to be abundant in the HC group, may play a role in preventing the progression of CRC. In particular, lactate-producing bacteria, which were found to be less abundant in healthy male controls may contribute to the higher incidence of CRC in males.

Keywords

Age distributionBiomarkersColorectal neoplasmsGastrointestinal microbiomeSex

Figures

**Fig. 1** Analysis scheme. Gut microbiome data were obtained from fecal samples of 56 participants, including 21 healthy controls, 21 patients with colorectal adenoma, and 14 patients with colorectal cancer. Patients were further classified into two groups based on sex (male and female) and age (≤55 and >55 years).

**Fig. 2** Distribution of gut microbiome features according to sex in the HC, AD, and CRC subjects. (A-D) Gut microbiota compositions at the phylum level. (A) Bar graph for taxonomic composition. (B-D) Scatter plots for relative taxonomic abundance in HC (B), AD (C), and CRC (D) groups. Data are expressed as the mean±SEM. (E-G) Linear discriminant analysis (LDA) effect size (LEfSe) analysis according to sex in the HC (E), AD (F), and CRC (G) groups. HC, healthy control; AD, colorectal adenoma; CRC, colorectal adenocarcinoma; SEM, standard error of the mean; F/B, Firmicutes to Bacteroidetes. *Lactate-producing bacteria; ^†Butyrate-producing bacteria.

**Fig. 3** Identification of taxonomic biomarkers. Linear discriminant analysis (LDA) effect size (LEfSe) analysis according to age in the HC (A), AD (B), and CRC (C) groups. HC, healthy control; AD, colorectal adenoma; CRC, colorectal adenocarcinoma. *Lactate-producing bacteria; ^†Butyrate-producing bacteria.

**Fig. 4** Distribution of gut microbiome features according to the HC-AD-CRC sequence in all participants. (A) Beta diversity of gut microbiota. (B-G) Gut microbiota compositions at the phylum level. Bar graph for taxonomic composition (B) and scatter plots for relative taxonomic abundance (C-G). Data are expressed as the mean±SEM. HC, healthy control; AD, colorectal adenoma; CRC, colorectal adenocarcinoma; SEM, standard error of the mean; NS, not significant. *p<0.01, ^†q<0.01.

**Fig. 5** Venn diagrams based on linear discriminant analysis (LDA) effect size (LEfSe) data (Supplementary Figs. 5-7). (A) Identification of bacteria exhibiting changes after colorectal disease progression compared to HC control in all participants. (B) Identification of bacteria exhibiting changes between male subjects with colorectal disease progression and male HCs. (C) Identification of bacteria exhibiting changes between female subjects with colorectal disease progression and female HCs. HC, healthy control; AD, colorectal adenoma; CRC, colorectal adenocarcinoma. *Lactate-producing bacteria; ^†Butyrate-producing bacteria.

**Fig. 6** Linear discriminant analysis (LDA) effect size (LEfSe) analysis according to sex in younger healthy control (HC) than 55 years of age. (A) Analysis scheme. (B) LEfSe analysis according to sex in younger HC subjects. *Lactate-producing bacteria.

**Fig. 7** Summary of the gut microbiome features depending on sex, age, and colorectal carcinogenesis progression based on human fecal sample analysis.

그림 출처: PubMed Central 공개 논문 (PMC11249946)

Conflict of interest statement

CONFLICTS OF INTEREST . No potential conflict of interest relevant to this article was reported.

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