Scientists use bile to transform bacteria to cure damaged colon

Researchers have identified a specific gut bacteria that can alter treatments for ulcerative colitis by restoring the colon’s ability to heal itself, thereby alleviating this debilitating inflammatory bowel disease.

The study, published on March 10 in EMBO Molecular Medicine, reveals how bacteria are called Clostridium Convert primary bile acids into special compounds that accelerate intestinal healing after injury. This represents a significant shift in conventional treatments that focus primarily on suppressing inflammation rather than promoting tissue repair.

“Our findings highlight the potential of microbiome-targeted strategies to regulate bile acid metabolism and promote gut healing,” said Antoine Jalil, the first author of the study.

Loss in intestinal diseases

Ulcerative colitis affects about 1 million Americans worldwide, adding millions of dollars to the world. This condition can cause pain, inflammation and ulcers in the lining of the large intestine, causing symptoms to seriously affect the quality of life.

Despite treatment progress, about 25% of cases remain under control and often require immunosuppressive drugs that pose significant risks, including severe infections and increased sensitivity to cancer.

A team led by Kristina Schoonjans and Rizlan Bernier-Latmani of EPFL found that patients with ulcerative colitis often have lower special bile acids, which are compounds that are made of gut bacteria, specifically called 7α-deoxydeoxydeoxybilic acids.

These molecules are not produced directly by the human body, but are caused by bacterial metabolism in the intestines. Previous studies have shown that the levels of patients with ulcerative colitis have significantly decreased, but their levels are not fully understood.

Bacterial Therapist

Researchers focus on ClostridiumIt is a human intestinal bacteria that specializes in converting primary bile acids produced by the liver into these 7α-hydroxylated varieties. Using various mouse models, they tested whether introducing the bacteria could improve recovery from experimentally induced colitis.

The results are excellent. Received mouse Clostridium Compared with the control group, it showed significantly faster recovery, maintained better colon integrity, and showed enhanced intestinal barrier function. Weight is a key indicator of disease severity and returns to normal faster in treated mice.

Microscopy showed that the number of proliferating cells in the treated mice increased in colonic crypts – evidence of active tissue regeneration and repair. This regenerative effect was observed when the bacteria were given before the induction of colitis (preventive method) and after the occurrence of injury (treatment method).

Receptor-mediated healing

To understand the mechanisms of these effects, the team conducted experiments using mice lacking a specific receptor called TGR5, which responds to bile acids. Protective effect Clostridium Disappeared in these mice, confirming that bacteria act through this signaling pathway.

“Clostridium Colonization protected TGR5 wild-type rather than knocking out TGR5 knockout mice from chemically induced epithelial lesions. ” The researchers noted in their research summary.

The researchers also conducted detailed analysis of gene expression in mouse models and human data. They found that in patients with ulcerative colitis, genes involved in intestinal cell renewal and differentiation had a strong positive correlation with 7α-dehydroxylated bile acid levels, providing further evidence for the link between these bacterial products and intestinal healing.

A new treatment

Making this finding particularly promising is that it provides a fundamentally different approach to treat ulcerative colitis. Current treatments focus primarily on inflammation, and this approach focuses on enhancing the natural healing process of the intestine.

Previous attempts to develop drugs targeting TGR5 receptors have been hampered by unnecessary side effects such as swelling of the gallbladder and cardiovascular problems. The researchers suggest that using bacteria to produce TGR5-activated compounds directly in the gut can provide a more targeted treatment with less systemic effects.

Bacterial-based approaches also address the destruction of microbiome (malnutrition) characteristics of ulcerative colitis, and may also restore a more balanced microbial environment while promoting healing.

From laboratory to treatment

Although the findings are promising, translating them into clinical applications will require further research. Researchers were able to successfully colonize mice Clostridiumbut noted that this often requires pretreatment with antibiotics to create space in the gut ecosystem, which makes practical applications in humans likely complex.

However, the researchers noted that when combined with pretreatment of vancomycin, colonization and effectiveness of hard-based biological treatment products improved the human phase 1B trial in patients with mild to moderate ulcerative colitis. This suggests that a similar approach may be feasible ClostridiumBased on therapy.

The potential benefits go beyond ulcerative colitis until other diseases involving intestinal damage, including Crohn’s disease and potential intestinal damage to radiation therapy or certain drugs.

“manage Clostridium Therefore, it may be a promising biotherapeutic strategy that can promote mucosal healing after colonic injury by restoring bile acid homeostasis. ” the researchers concluded.

As researchers continue to explore the therapeutic potential of microbiome-based interventions, this work highlights how to understand the complex relationship between gut bacteria and human health may lead to novel treatments related to the natural processes of the human body, rather than conducting them.