Cattolica-Gemelli

Cancer: can antibiotics affect the effectiveness of immunotherapy?

Study highlights a 49 per cent higher risk of mortality. Possible link to the gut microbiota: but for now, it is impossible to prove a cause-and-effect relationship

by Health Editorial Team

27 October 2026

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5' min read

Translated by AI

Versione italiana

Key points

One in three patients is prescribed antibiotics during immunotherapy
The window of opportunity: two months before treatment
Is it down to antibiotics or the frailty of the patients?
The role of the gut microbiota
From research to treatment: what changes for patients

5' min read

Translated by AI

Versione italiana

Antibiotics are life-saving medicines, but they may also be a significant negative factor in the response to cancer immunotherapy. This is suggested by one of the most extensive meta-analyses conducted to date on the subject, which examined 116 patient cohorts, comprising a total of 97,850 people with cancer, treated with immunotherapy across 29 countries. The findings, published in the prestigious scientific journal *Cancer Cell*, document a significant association between exposure to antibiotics and poorer cancer outcomes. This is a sign that warrants attention, but it does not justify concluding that antibiotics are responsible for reduced treatment efficacy.

The study, entitled “Antibiotics and outcomes of cancer immunotherapy: an updated meta-analysis and clinical applications”, is the result of an international collaboration involving, amongst others, Professor Gianluca Ianiro, a researcher in Gastroenterology at the Catholic University of the Sacred Heart and a senior consultant at the CEMAD Clinical Unit of the A. Gemelli University Polyclinic Foundation IRCCS, who is the senior co-author and corresponding author of the paper alongside Professor Laurence Zitvogel of the Gustave Roussy Institute in Paris. The authors also include numerous researchers from the Gemelli and the Catholic University, amongst whom Dr Serena Porcari, co-first author, Professor Antonio Gasbarrini, Professor of Internal Medicine at the Catholic University of the Sacred Heart and Scientific Director of the Gemelli University Hospital Foundation IRCCS, and Professor Giampaolo Tortora, Professor of Oncology at the Catholic University and Director of the Gemelli Comprehensive Cancer Centre.

One in three patients is prescribed antibiotics during immunotherapy

The analysis shows that almost one in three patients receives antibiotics during the course of immunotherapy. In the population analysed, 31.2 per cent of patients had been exposed to these drugs shortly before the start of cancer treatment. Compared with patients who had not been exposed to antibiotics, those treated with them had a 49 per cent higher risk of death (hazard ratio, HR, 1.49) and a 44 per cent higher risk of disease progression or death (HR 1.44) during the observation period. “These figures,” explains Professor Gasbarrini-, “must be interpreted with care. This is a relative risk: it indicates that, during the observation period, the risk of death among patients exposed to antibiotics was approximately one and a half times that of those not exposed. It does not mean that antibiotics increase the absolute probability of dying by 49 per cent. To give an example, if, over a certain period, 10 out of 100 patients in the unexposed group died, approximately 14–15 would die in the exposed group: a real difference, but of just a few percentage points, not 49 per cent. Similarly, the figure does not indicate that immunotherapy is 49 per cent less effective: the comparison relates to different groups of patients, not the efficacy of the drug, and measures an association, not a cause-and-effect relationship.”

The time frame to consider: two months before treatment

One of the most interesting aspects concerns the timing of antibiotic administration. The association with adverse outcomes was particularly marked in patients who had received antibiotic treatment in the 60 days prior to the start of immunotherapy: in this subgroup, the risk of reduced survival or more rapid disease progression reached 79 per cent and 57 per cent respectively.

“This finding suggests the existence of a potentially particularly critical time window,” observes Professor Ianiro, “but it does not allow us to determine whether bringing forward, postponing or avoiding a course of antibiotics might alter the oncological prognosis for these patients. The differences observed between the various periods of exposure could, in fact, also be influenced by patient characteristics and methodological biases inherent in retrospective studies.”

Is it down to antibiotics or the frailty of the patients?

The key question the researchers sought to address is whether the cause lies with antibiotics or with the patients’ greater frailty. Those who require antibiotics may have infections, more complex clinical conditions or greater general frailty – all factors that can adversely affect survival, regardless of the efficacy of immunotherapy.

To explore this possibility, the authors carried out a specific analysis of 7,684 patients in good general health (classified as having an ECOG performance status of 0–1). In this group, too, the association remained evident, with an HR of 1.43 for both overall survival and progression-free survival.

“The fact that this association persists even in patients in good general health,” continues Ianiro, “suggests that clinical frailty may not be the only explanation. However, this finding does not prove a causal effect of antibiotics. It is a factor that makes it all the more important to investigate the possible biological mechanisms in greater depth.”

The role of the gut microbiota

One of the most fascinating theories regarding the interpretation of these findings concerns the billions of microorganisms that inhabit our gut. We now know that the microbiota not only performs digestive and metabolic functions, but also helps to regulate the immune system, including certain mechanisms involved in the response to cancer treatments.

Antibiotics can profoundly alter this ecosystem, reducing certain bacterial populations that may be beneficial to the immune response whilst promoting others. Experimental studies have identified several mechanisms through which these alterations could interfere with the activity of immune checkpoint inhibitors (immunotherapy), drugs that help the immune system to recognise and combat cancer cells.

The proposed mechanisms include changes in the gut microbiota, alterations in T-cell activation, and changes in the intestinal blood-gut barrier and in the production of microbial metabolites, all of which are capable of influencing anti-tumour immunity.

It is, however, essential to distinguish between experimental evidence and clinical findings. This meta-analysis did not include direct measurements of the composition of patients’ microbiota and cannot therefore demonstrate that antibiotic-induced alterations are responsible for the lower survival rates observed. It also remains possible that direct effects of the drugs or other factors that were not adequately measured may be at play.

From research to treatment: what changes for patients

“For the time being, there is no reason to stop using antibiotics when they are necessary,” explains Professor Tortora. “In cancer patients, bacterial infections can be a serious complication requiring prompt treatment, which is sometimes essential for survival. The message that emerges from this study is rather to promote the appropriate use of antibiotics, avoiding unnecessary prescriptions and favouring, where clinically possible, targeted treatments, in accordance with the principles of antibiotic stewardship. However, based on this meta-analysis, there is insufficient evidence to identify one class of antibiotics as safer than another with regard to the outcomes of immunotherapy: the available data did not allow for reliable comparisons by individual class, route of administration or duration of treatment.”

This research therefore opens up an important avenue of inquiry, whilst not yet providing definitive answers. To understand whether antibiotics are simply an indicator of more unfavourable clinical conditions or whether, on the other hand, they directly contribute to altering the response to immunotherapy, future prospective studies will be needed that are capable of following patients over time, accurately documenting antibiotic treatments and analysing changes in the composition of the gut microbiota.

“This is precisely the direction in which research at the Policlinico Gemelli is heading – reveals Professor Ianiro – where a cohort study involving cancer patients is currently being prepared, with the aim of characterising the changes in the microbiota associated with exposure to antibiotics and correlating them with the outcomes of immunotherapy.”

“Above all, this work gives rise to new research hypotheses,” concludes Professor Gasbarrini. “We have identified a significant association, confirmed across a very large sample size, but we still need to understand to what extent these results depend on the patients’ conditions and to what extent, if at all, on a direct biological effect of the antibiotics. The next step will be to study the microbiota directly and track its evolution during treatment, to ascertain whether this association conceals a mechanism that can be targeted. The future aim is to understand whether protecting or restoring the balance of the microbiota could become a complementary strategy for improving the response to immunotherapy. This is a promising hypothesis, to be verified through appropriate clinical trials, which could help open up a new frontier in personalised cancer medicine.”