Abstract
Immune checkpoint inhibitors (icis) are increasingly being used in clinical practice, improving outcomes for cancer patients. Preclinical models showed significant interaction between the gut microbiome (gm) and response to icis. However, that interaction remains unclear in clinical practice. We performed a systematic review in medline to determine■ whether antibiotics affect ici efficacy,■ whether baseline gm composition and ici efficacy show any correlations,■ whether baseline gm composition and emergence of immune-related adverse events (iraes) show any correlations, and■ whether gm manipulation can alleviate the iraes.Included publications had to be written in English or French and had to describe a quantifiable link between gm composition or its modification and the response to icis or the occurrence of iraes, or both. Of 1451 articles published before December 2018, 13 publications met the inclusion criteria. Five full-text articles and two abstracts highlighted a negative effect of antibiotics on ici efficacy. The composition of the gm was associated with ici efficacy in five full-text articles and one abstract, and with iraes in two full-text articles. In 2 cases, fecal microbiota transplantation was reported to reduce immune colitis. If possible, antibiotics should be avoided before ici treatment because of their negative effect on ici anticancer efficacy. No specific commensal bacterium was associated with ici efficacy, but an intact gm with high bacterial diversity and a good ratio of "responder-associated" bacteria to "non-responder-associated" bacteria seem to be correlated with better patient outcomes. Fecal microbiota transplantation is a promising technique for reducing ici-associated colitis.
Highlights
The human gut microbiome is composed of more than 100 trillion bacteria[1]
If possible, antibiotics should be avoided before ici treatment because of their negative effect on ici anticancer efficacy
No specific commensal bacterium was associated with ici efficacy, but an intact gm with high bacterial diversity and a good ratio of “responder-associated” bacteria to “non-responder-associated” bacteria seem to be correlated with better patient outcomes
Summary
The human gut microbiome (gm) is composed of more than 100 trillion bacteria[1]. The gm is highly individual, but can be affected by several external factors such as diet[2], antibiotics[3,4], and treatment with proton-pump inhibitors[5].The composition of the gm is known to play a key role in the development of multiple diseases[6,7] including inflammatory bowel disease[8,9], diabetes mellitus[10], and obesity[2]. The human gut microbiome (gm) is composed of more than 100 trillion bacteria[1]. The gm is highly individual, but can be affected by several external factors such as diet[2], antibiotics[3,4], and treatment with proton-pump inhibitors[5]. The gm composition has been implicated in the development of cancers such as colorectal cancer[11]: the presence of certain bacteria, such as Fusobacterium nucleatum appears to be a predictive factor in colorectal cancer development[12,13]. Immune checkpoint inhibitors (icis) are increasingly being used in clinical practice, improving outcomes for cancer patients. Preclinical models showed significant interaction between the gut microbiome (gm) and response to icis. That interaction remains unclear in clinical practice
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