3D illustration of Clostridium scindens in the intestine.
3D illustration of Clostridium scindens in the intestine.
Researchers have identified a specific gut bacterium that could transform treatment approaches for ulcerative colitis by restoring the colon’s ability to heal itself—potentially offering relief to millions suffering from this debilitating inflammatory bowel disease.
The study, published March 10 in EMBO Molecular Medicine, reveals how a bacterium called Clostridium scindens converts primary bile acids into specialized compounds that accelerate intestinal healing after injury. This represents a significant shift from conventional treatments that focus primarily on suppressing inflammation rather than promoting tissue repair.
“Our findings highlight the potential of microbiome-targeted strategies to modulate bile acid metabolism and promote gut healing,” said Antoine Jalil, the study’s first author from EPFL (École Polytechnique Fédérale de Lausanne).
Missing Molecules in Gut Disease
Ulcerative colitis affects approximately 1 million Americans and millions more worldwide, with rates rising globally. The condition causes painful inflammation and ulceration of the large intestine’s lining, leading to symptoms that can severely impact quality of life.
Despite advances in treatment, about 25% of cases remain poorly controlled, often requiring immunosuppressive medications that carry significant risks including serious infections and increased cancer susceptibility.
The research teams, led by Kristina Schoonjans and Rizlan Bernier-Latmani at EPFL, discovered that ulcerative colitis patients typically have lower levels of special bile acids that are processed by gut bacteria—specifically, compounds called 7α-dehydroxylated bile acids.
These molecules aren’t produced directly by the body but instead result from bacterial metabolism in the gut. Previous research had shown their levels are notably reduced in patients with ulcerative colitis, but the implications weren’t fully understood.
The Bacterial Healer
The researchers focused on Clostridium scindens, a human gut bacterium that specializes in converting primary bile acids produced by the liver into these 7α-dehydroxylated varieties. Using various mouse models, they tested whether introducing this bacterium could improve recovery from experimentally induced colitis.
The results were remarkable. Mice receiving Clostridium scindens showed significantly faster recovery, maintained better colon integrity, and demonstrated enhanced intestinal barrier function compared to control groups. Body weight, a key indicator of disease severity, returned to normal more quickly in treated mice.
Microscopic examination revealed that the treated mice had increased numbers of proliferating cells in their colonic crypts—evidence of active tissue regeneration and repair. This regenerative effect was observed both when the bacterium was administered before colitis induction (preventative approach) and when given after damage had occurred (therapeutic approach).
Receptor-Mediated Healing
To understand the mechanism behind these effects, the team conducted experiments using mice lacking a specific receptor called TGR5, which responds to bile acids. The protective effects of Clostridium scindens disappeared in these mice, confirming that the bacterium works through this signaling pathway.
“Clostridium scindens colonization protected Tgr5 wild-type, but not Tgr5 knock-out mice from chemically-induced epithelial injury,” the researchers noted in their study synopsis.
The researchers also performed detailed analysis of gene expression in both mouse models and human data. They found that in ulcerative colitis patients, genes involved in intestinal cell renewal and differentiation showed a strong positive correlation with 7α-dehydroxylated bile acid levels, providing further evidence for the link between these bacterial products and gut healing.
A New Therapeutic Approach
What makes this discovery particularly promising is that it offers a fundamentally different approach to treating ulcerative colitis. Current treatments primarily target inflammation, while this approach focuses on enhancing the gut’s natural healing processes.
Previous attempts to develop drugs targeting the TGR5 receptor have been hampered by unwanted side effects like gallbladder swelling and cardiovascular issues. The researchers suggest that using bacteria to produce TGR5-activating compounds directly in the gut could provide more targeted therapy with fewer systemic effects.
The bacteria-based approach also addresses the disrupted microbiome (dysbiosis) that characterizes ulcerative colitis, potentially restoring a more balanced microbial environment while simultaneously promoting healing.
From Lab to Treatment
While the findings are promising, translating them into clinical applications will require further research. The researchers were able to successfully colonize mice with Clostridium scindens, but noted that this often required pretreatment with antibiotics to create space in the gut ecosystem—suggesting that practical application in humans might be complex.
However, the researchers point to a human phase 1b trial that showed improved colonization and effectiveness of a Firmicute-based biotherapeutic product when combined with vancomycin preconditioning to induce remission in mild to moderate ulcerative colitis patients. This suggests that similar approaches might be viable for Clostridium scindens-based therapies.
The potential benefits extend beyond ulcerative colitis to other conditions involving intestinal damage, including Crohn’s disease and potentially gut injuries from radiation therapy or certain medications.
“Administration of Clostridium scindens could therefore be a promising biotherapeutic strategy to foster mucosal healing following colon 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 understanding the complex relationships between gut bacteria and human health could lead to novel treatment approaches that work with the body’s natural processes rather than against them.
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