Altered gut microbiota of obesity subjects promotes colorectal carcinogenesis in mice

Kang, Xing; Ng, Siu-Kin; Liu, Changan; Lin, Yufeng; Zhou, Yunfei; Kwong, Thomas; Ni, Yun‐Bi; Lam, Thomas Y.; Wu, William Ka Kei; Wei, Hong; Sung, Joseph J.Y.; Yu, Jun; Wong, Sunny Hei

doi:10.1016/j.ebiom.2023.104670

Cited by 9 publications

(4 citation statements)

References 41 publications

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“…FISH was performed as described in previous reports [ 24 , 25 ]. Colon tissues were washed with PBS, fixed with 10% formalin solution, embedded in paraffin, and cut into 5 μm-thick slices, which were incubated overnight at 50 °C with a fluorescein-conjugated probe against S. moorei (5′–CCT TAC AAA CAA GAG CTT TTA CA–3′).…”

Section: Methodsmentioning

confidence: 99%

“…Colon tissues slices were stained with hematoxylin and eosin for histologic diagnosis by an experienced pathologist who was unaware of the treatment allocation of the mice. Inflammation was assessed by infiltration of inflammatory cells into the epithelium, whereas dysplasia was defined by the presence of hyperchromasia, nuclear pleomorphism, increased nuclear-to-cytoplasmic ratios, and atypical mitotic figures [ 24 , 25 ].…”

Section: Methodsmentioning

confidence: 99%

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Solobacterium moorei promotes the progression of adenomatous polyps by causing inflammation and disrupting the intestinal barrier

Yu,

Wang,

et al. 2024

J Transl Med

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Background Adenomatous polyps (APs) with inflammation are risk factors for colorectal cancer. However, the role of inflammation-related gut microbiota in promoting the progression of APs is unknown. Methods Sequencing of the 16S rRNA gene was conducted to identify characteristic bacteria in AP tissues and normal mucosa. Then, the roles of inflammation-related bacteria were clarified by Spearman correlation analysis. Furthermore, colorectal HT-29 cells, normal colon NCM460 cells, and azoxymethane-treated mice were used to investigate the effects of the characteristic bacteria on progression of APs. Results The expression levels of inflammation-related markers (diamine oxidase, d-lactate, C-reactive protein, tumor necrosis factor-α, interleukin-6 and interleukin-1β) were increased, whereas the expression levels of anti-inflammatory factors (interleukin-4 and interleukin-10) were significantly decreased in AP patients as compared to healthy controls. Solobacterium moorei (S. moorei) was enriched in AP tissues and fecal samples, and significantly positively correlated with serum inflammation-related markers. In vitro, S. moorei preferentially attached to HT-29 cells and stimulated cell proliferation and production of pro-inflammatory factors. In vivo, the incidence of intestinal dysplasia was significantly increased in the S. moorei group. Gavage of mice with S. moorei upregulated production of pro-inflammatory factors, suppressed proliferation of CD4+ and CD8+cells, and disrupted the integrity of the intestinal barrier, thereby accelerating progression of APs. Conclusions S. moorei accelerated the progression of AP in mice via activation of the NF-κB signaling pathway, chronic low-grade inflammation, and intestinal barrier disruption. Targeted reduction of S. moorei presents a potential strategy to prevent the progression of APs.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Solobacterium moorei promotes the progression of adenomatous polyps by causing inflammation and disrupting the intestinal barrier

Yu,

Wang,

et al. 2024

J Transl Med

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“…The proportion of Hafnia alvei belonging to the Proteobacteria phylum and that of Akkermansia muciniphila belonging to the Verrucomicrobia phylum increase in obesity and CRC patients 24 . In a recent study, AOM-treated APC Min/ + mice transplanted with feces from obese individuals exhibited increased colon tumor formation 25 . This observation implies that alterations in the gut microbial composition induced by obesity may impact the susceptibility to colorectal cancer.…”

Section: Introductionmentioning

confidence: 94%

Sex differences in colonic gene expression and fecal microbiota composition in a mouse model of obesity-associated colorectal cancer

Chang,

Kang,

Lee

et al. 2024

Sci Rep

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This study investigated the sex-specific correlation between obesity and colorectal cancer emphasizing a more pronounced association in males. Estrogen, chromosomal genes, and gut bacteria were assessed in C57BL6/J male, female and ovariectomized (OVX) female mice, subjected to either a low-fat diet (LFD) or high-fat diet (HFD) for 14 weeks. Induction of colon tumor involved azoxymethane (10 mg/kg) administration, followed by three cycles of dextran sulfate sodium. Male mice on HFD exhibited higher final body weight and increased colon tumors compared to females. Colonic mucin 2 expression was significantly higher in females. HFD-modulated differentially expressed genes numbered 290 for males, 64 for females, and 137 for OVX females. Only one up-regulated gene (Gfra3) overlapped between females and OVX females, while two down-regulated genes (Thrsp and Gbp11) overlapped between males and OVX females. Genes up-regulated by HFD in males were linked to cytokine-cytokine interaction, HIF-1 signaling pathway, central carbon metabolism in cancer. Sex-specific changes in gut microbial composition in response to HFD were observed. These findings suggest a male-specific vulnerability to HFD-induced colon tumor formation, implicating key genes and colonic bacteria in colon tumorigenesis.

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“…A. muciniphila is negatively associated with obesity, diabetes, cardiovascular disease, and low-grade inflammation ( Plovier et al, 2017 ; Depommier et al, 2019 ; Yang et al, 2019 ; Yoon et al, 2021 ). In recent years, it has been discovered that various bacteria are associated with the development and treatment of CRC ( Zheng et al, 2019 ; Jiang et al, 2023 ; Kang et al, 2023 ). A. muciniphila is considered one of the most promising bacteria for suppressing tumors in CRC due to its multiple mechanisms of colorectal cancer inhibition.…”

Section: Facultative Anaerobes-based Drug Delivery Systemsmentioning

confidence: 99%

Advances in anti-tumor based on various anaerobic bacteria and their derivatives as drug vehicles

Song,

Yang,

Chen

et al. 2023

Front. Bioeng. Biotechnol.

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Cancer therapies, such as chemotherapy and radiotherapy, are often unsatisfactory due to several limitations, including drug resistance, inability to cross biological barriers, and toxic side effects on the body. These drawbacks underscore the need for alternative treatments that can overcome these challenges and provide more effective and safer options for cancer patients. In recent years, the use of live bacteria, engineered bacteria, or bacterial derivatives to deliver antitumor drugs to specific tumor sites for controlled release has emerged as a promising therapeutic tool. This approach offers several advantages over traditional cancer therapies, including targeted drug delivery and reduced toxicity to healthy tissues. Ongoing research in this field holds great potential for further developing more efficient and personalized cancer therapies, such as E. coli, Salmonella, Listeria, and bacterial derivatives like outer membrane vesicles (OMVs), which can serve as vehicles for drugs, therapeutic proteins, or antigens. In this review, we describe the advances, challenges, and future directions of research on using live bacteria or OMVs as carriers or components derived from bacteria of delivery systems for cancer therapy.

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Altered gut microbiota of obesity subjects promotes colorectal carcinogenesis in mice

Cited by 9 publications

References 41 publications

Solobacterium moorei promotes the progression of adenomatous polyps by causing inflammation and disrupting the intestinal barrier

Solobacterium moorei promotes the progression of adenomatous polyps by causing inflammation and disrupting the intestinal barrier

Sex differences in colonic gene expression and fecal microbiota composition in a mouse model of obesity-associated colorectal cancer

Advances in anti-tumor based on various anaerobic bacteria and their derivatives as drug vehicles

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