Understanding and mitigating the side effects of chemotherapy is a central goal of cancer research, as managing treatment-related toxicity directly affects the ability to maintain therapies over time at the intended doses. Among the organs most affected by chemotherapy is the intestine: gastrointestinal complications can significantly impair patients’ quality of life and, in more severe cases, require treatment modifications or dose reductions. One of the most common manifestations is intestinal mucositis, an inflammatory condition that damages the intestinal mucosa and disrupts the integrity of the intestinal barrier, leading to gastrointestinal symptoms and reducing treatment tolerability.

A new study published in the journal Gut Microbes investigated how rifaximin, a non-absorbable antibiotic, may help protect the intestine during chemotherapy through modulation of the microbiota. The study identified Muribaculum, a microorganism naturally present in the gut, as a potential mediator of the protective effects observed on the intestinal barrier.

The study was conducted by researchers from the Humanitas Research Hospital. The first authors are Carmen Correale, Technician at Humanitas Research Hospital, and Martina Morandi, who was pursuing her PhD at the same institution during the study. The corresponding authors are Paola Brescia, Senior Postdoctoral Researcher at Humanitas Research Hospital and Assistant Professor at Humanitas University, and Maria Rescigno, Professor of General Pathology at Humanitas University, Head of the Mucosal Immunology and Microbiota Laboratory at Humanitas Research Hospital, and Scientific Director of the CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences in Vienna.

“For a long time, the intestinal side effects of chemotherapy were considered an unavoidable consequence of treatment. Today, however, we know that the microbiota can significantly influence the intestine’s ability to respond and adapt to these stresses. Understanding these mechanisms opens the door to new strategies for protecting patients without compromising the effectiveness of anticancer therapies,” says Maria Rescigno.

Protecting the intestinal barrier during chemotherapy

One of the key questions addressed by the study was whether it is possible to protect the intestine from the harmful effects of chemotherapy without interfering with the activity of anticancer drugs.

To investigate this, the researchers used an experimental model of intestinal injury induced by 5-fluorouracil (5-FU), one of the most widely used chemotherapy agents in oncology, and evaluated the potential protective role of rifaximin.

The results showed that pretreatment with rifaximin can reduce inflammation and damage to the intestinal mucosa, helping preserve the integrity of the intestinal barrier and limiting the passage of potentially harmful substances into the bloodstream, without affecting the antitumor activity of 5-FU.

“What makes this finding particularly interesting is the possibility of improving treatment tolerability without altering its anticancer efficacy,” explains Paola Brescia. “It is a delicate but essential balance when considering support strategies that can be truly beneficial in clinical practice.”

The microbiota as a mediator of the protective effect

To determine whether the observed effects might also be relevant in humans, the researchers used an ex vivo culture system of human intestinal tissue (EVOC), which preserves the architecture and key functional characteristics of the intestinal mucosa. In this model, rifaximin demonstrated the ability to maintain tissue structure even under inflammatory stimulation, preserving mucus homeostasis and the function of the cellular junctions that regulate the intestinal barrier.

At the same time, the study further explored the role of the microbiota to determine whether these effects could also be linked to changes in its composition. The analysis revealed that rifaximin does not merely exert a direct effect on the tissue but also reshapes the intestinal microbial community, preventing the loss of certain species associated with a healthy state, including Muribaculum and Parasutterella. This suggests that the observed benefits may be at least partly mediated by the microbiota.

In this context, a particularly interesting finding concerns Muribaculum intestinale. Supplementation with this bacterium reduced intestinal damage induced by 5-fluorouracil, suggesting that specific members of the microbiota may contribute to intestinal barrier protection during chemotherapy.

“One of the most interesting aspects of the study is that supplementation with Muribaculum intestinale was able to reproduce some of the protective effects observed with rifaximin,” says Carmen Correale. “This finding encourages us to reconsider the role of specific microbial species, not only as components of a complex ecosystem but also as contributors to intestinal barrier protection during chemotherapy and provides the basis for further research in this area.”

Research opening new perspectives

Taken together, the study’s findings identify Muribaculum as a microbial contributor to intestinal mucosal protection during chemotherapy and suggest that the microbiota could represent a strategic target for interventions aimed at improving the tolerability of cancer treatments.

This evidence opens new perspectives for the development of supportive approaches capable of preserving intestinal function during chemotherapy, with potential clinical implications for the management of cancer patients.