A probiotic Limosilactobacillus fermentum GR-3 mitigates colitis-associated tumorigenesis in mice via modulating gut microbiome

Bacterial therapy for colorectal cancer (CRC) represents a burgeoning frontier. The probiotic Limosilactobacillus fermentum GR-3, derived from traditional food “Jiangshui”, exhibited superior antioxidant capacity by producing indole derivatives ICA and IPA. In an AOM/DSS-induced CRC mouse model, GR-...

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Published in:NPJ science of food 2024-09, Vol.8 (1), p.61-16, Article 61
Main Authors: Zhou, Tuoyu, Wu, Jingyuan, Khan, Aman, Hu, Tianxiang, Wang, Yiqing, Salama, El-Sayed, Su, Shaochen, Han, Huawen, Jin, Weilin, Li, Xiangkai
Format: Article
Language:English
Subjects:
631/326/2565/2134
631/326/41/2533
631/67/1504
Acids
Antioxidants
Apoptosis
Ascorbic acid
Bile acids
Cancer therapies
Chemistry
Chemistry and Materials Science
Chemistry/Food Science
Colitis
Colon
Colorectal cancer
Colorectal carcinoma
Digestive system
Fermented food
Food
Food Microbiology
Food Science
Gastrointestinal tract
Indoles
Inflammatory bowel disease
Intestinal microflora
Limosilactobacillus fermentum
Metabolites
Metagenomics
Microbiomes
Microbiota
Nutrition
Oxidative stress
Probiotics
Radiation therapy
Strain analysis
Surgery
Traditional foods
Tumorigenesis
Vitamin C
Weight loss
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Summary:Bacterial therapy for colorectal cancer (CRC) represents a burgeoning frontier. The probiotic Limosilactobacillus fermentum GR-3, derived from traditional food “Jiangshui”, exhibited superior antioxidant capacity by producing indole derivatives ICA and IPA. In an AOM/DSS-induced CRC mouse model, GR-3 treatment alleviated weight loss, colon shortening, rectal bleeding and intestinal barrier disruption by reducing oxidative stress and inflammation. GR-3 colonization in distant colon induced apoptosis and reduced tumor incidence by 51.2%, outperforming the control strain and vitamin C. The beneficial effect of GR-3 on CRC was associated with gut microbiome modulation, increasing SCFA producer Lachnospiraceae NK4A136 group and suppressing pro-inflammatory strain Bacteroides . Metagenomic and metabolic analyses revealed that GR-3 intervention upregulated antioxidant genes ( xseA , ALDH ) and butyrate synthesis gene ( bcd ), while increasing beneficial metabolites (SCFAs, ICA, IPA, VB12 and VD3) and reducing harmful secondary bile acids. Overall, GR-3 emerges as a promising candidate in CRC therapy, offering effective gut microbiome remediation.
ISSN:2396-8370
2396-8370
DOI:10.1038/s41538-024-00307-5