Gut Microbiota #15

GUT MICROBIOTA MODULATES RESPONSE TO PROSTATE CANCER TREATMENT

^{Pernigoni N, Zagato E, Calcinotto A, et al. Commensal bacteria promote endocrine resistance in prostate cancer through androgen biosynthesis. Science 2021 Oct 8;374(6564):216-224.}

Prostate cancer (PC) is one of the most common cancers in males. Because tumors growth and progression depend on androgen levels, androgen deprivation therapy (ADT), surgical or chemical castration is used to treat patients with PC. However, some of them develop a castration- resistant prostate cancer (CRPC) which result in tumor progression and new treatment strategy are under investigation. Since recent studies have highlighted the role of microbiota in both cancer development and therapy success, the authors used PC mouse models and patient data to examine the role of gut microbiota in PC carcinogenesis. Enrichment of Ruminococcus spp. and Bacteroides acidifaciens was detected after development of CRPC but gut microbiota ablation slowed tumor growth in CRPC mice. Castration resistant (CR) fecal microbiota transplantation (FMT) from castration-resistant (CR) mice and R. gnavus administration led to increased circulating androgen levels and increased PC growth and CRPC development. PC growth was controlled by FMT from hormone sensitive PC individuals and Prevotella stercorea administration. CRPC patients had enrichment of Ruminococcus and Bacteroides genera associatied with poor outcome while hormone- sensitive PC patients had higher abundance of Prevotella genus linked with more favorable outcome.

Commensal gut microbiota in androgen- deprived patients and mice produce androgens that promote PC growth and the development of CRPC via systemic circulation. Modulation of gut microbiota could theoretically be used as additional therapy for PC.

THE ASSOCIATION BETWEEN GUT DYSBIOSIS AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE

^{Li N, Dai Z, Wang Z, et al. Gut microbiota dysbiosis contributes to the development of chronic obstructive pulmonary disease. Respir Res 2021 Oct 25;22(1):274.}

Chronic obstructive pulmonary disease (COPD) refers to lung diseases (emphysema, bronchitis and asthma) characterized by progressive respiratory distress. Recent studies have revealed changes in the gut microbiota linked to disease development in the lungs. While primarily considered a respiratory disease, COPD commonly co-occurs with chronic gastrointestinal tract diseases. In the present study, the authors took an interest in the the gut-lung axis linked to COPD. Stool analyses have revealed that patients with severe COPD had lower abundance of Bacteroidetes but higher abundance of Firmicutes. Of bacterial families, Prevotellaceae abundance was higher in mild COPD, whereas Bacteroidaceae and Fusobacteriaceae abundancies were lower in severe COPD compared to healthy controls. Short chain fatty acid (SCFA) levels were significantly lower in severe COPD. Fecal microbiota transfer (FMT) to mice from COPD patients caused a significant weight reduction and airway mucus hypersecretion in mice. Acceleration of lung function decline was detected in FMT mice during biomass smoke exposure. This study revealed that COPD patients have gut microbiota dysbiosis with reduced SCFA levels. These changes are possibly linked to airway inflammation and COPD progression.

THE IMPACT OF COMEDICATION ON THE TREATMENT EFFICACY OF IMMUNE CHECKPOINT INHIBITORS

^{Kostine M, Mauric E, Tison A, et al. Baseline co-medications may alter the anti-tumoural effect of checkpoint inhibitors as well as the risk of immune-related adverse effects. Eur J Cancer 2021 Nov;157:474-484.}

Immune checkpoint inhibitors (ICI) have dramatically improved the prognosis of several advanced cancers. Evidence have shown that gut microbiota may modulate the treatment response for ICI, and may also be involved in the pathogenesis of immune-related adverse events (IRAE). While antibiotics are known to deteriorate the prognosis of ICI treated cancer patients, little is known about the effect on the microbiota of various co-medications when given at ICI initiation. In the present study, the authors examined the effect of co-medications given 1 month before or after administration of ICI therapy on the treatment results and the occurrence of IRAE.

The use of antibiotics, glucocorticoids (daily dose > 10 mg), proton pump inhibitors, psychotropic drugs, morphine and insulin were associated with significantly shortened survival and decreased tumor response. Combination therapy with these drugs decreased survival more than monotherapy. These medications were also associated with decreased incidence of IRAE. Co-administration of statins, angiotensin-converting enzyme inhibitors and/or angiotensin II receptor blockers, non-steroidal anti-inflammatory drugs, aspirin and oral antidiabetic drugs did not impact patient survival. The present study showed that co-medication influences both to the response and IRAE of ICI treatment. The impact of co-medication may be mediated via microbiota or other immunomodulatory mechanisms. In clinical practice, baseline co-medications should be carefully assessed when ICI therapy is planned. Drugs with negative impact on ICI therapy should be avoided when possible.