The gut microbiota associated with high‐Gleason prostate cancer

Abstract

We have found that intestinal bacteria and their metabolites, short‐chain fatty acids (SCFAs), promote cancer growth in prostate cancer (PCa) mouse models. To clarify the association between gut microbiota and PCa in humans, we analyzed the gut microbiota profiles of men with suspected PCa. One hundred and fifty‐two Japanese men undergoing prostate biopsies (96 with cancer and 56 without cancer) were included in the study and randomly divided into two cohorts: a discovery cohort (114 samples) and a test cohort (38 samples). The gut microbiota was compared between two groups, a high‐risk group (men with Grade group 2 or higher PCa) and a negative + low‐risk group (men with negative biopsy or Grade group 1 PCa), using 16S rRNA gene sequencing. The relative abundances of Rikenellaceae, Alistipes, and Lachnospira, all SCFA‐producing bacteria, were significantly increased in high‐risk group. In receiver operating characteristic curve analysis, the index calculated from the abundance of 18 bacterial genera which were selected by least absolute shrinkage and selection operator regression detected high‐risk PCa in the discovery cohort with higher accuracy than the prostate specific antigen test (area under the curve [AUC] = 0.85 vs 0.74). Validation of the index in the test cohort showed similar results (AUC = 0.81 vs 0.67). The specific bacterial taxa were associated with high‐risk PCa. The gut microbiota profile could be a novel useful marker for the detection of high‐risk PCa and could contribute to the carcinogenesis of PCa.

The Effects and Mechanisms of Flavonoids on Cancer Prevention and Therapy: Focus on Gut Microbiota

“…The previous study revealed an increased in the count of proinflammatory Bacteroides and Streptococcus in patients with prostate cancer compared with healthy controls 95 . The numbers of Alistipes , Lachnospira , Rikenellaceae and SCFA-producing bacteria were positively associated with a high risk of prostate cancer 96 . It is likely that dysbiosis of gut microbiota may cause inflammation and neoplastic events even at a systemic level.…”

Prostate diseases and microbiome in the prostate, gut, and urine

“…Due to racial differences and heterogeneity in the microbiome among patients, its role in prostate carcinogenesis remains unclear, especially in Asian men. Several comparative analyses using stool samples or rectal swabs proved the compositional differences in bacteria between patients with PCa and healthy controls ( Table 3 ) 46 , 47 , 48 , 49 , 50 , 51 . Liss et al.…”

“…evaluated rectal swabs from 21 patients with PCa and demonstrated that Ruminococcaceae and Akkermansia muciniphila were more abundant in men taking oral androgen receptor axis-targeted therapies such as abiraterone acetate and enzalutamide 48 . A Japanese report found that Rikenellaceae , Alistipes , and Lachnospira (all short-chain fatty acid-producing bacteria) were significantly higher in those at a high risk (grade group ≥2) of PCa 50 . The same group previously reported that a high-fat diet and obesity promoted local prostate inflammation and cancer proliferation and that short-chain fatty acids and major metabolites of intestinal bacteria promoted PCa growth via the insulin growth factor-1 signaling pathway in a preclinical model.…”

“…The gut microbiota profile can be a novel tool for the detection of high-risk PCa. 50 Liu et al. (2020) Stool samples before and after castration-resistance 21 men with PCa treated with ADT 16S rRNA gene amplicon sequencing Differences in microbiota were determined with α/β-diversity and LefSe analysis.…”

Connecting the Dots Between the Gut–IGF-1–Prostate Axis: A Role of IGF-1 in Prostate Carcinogenesis

“…The examination of mice treated with antibiotics has revealed the absence of members of the family Rikenellaceae, order Clostridiales in the gut microbiota. Examination of the gut microbiota of men with a high-risk of PCa has revealed the increased abundance of genus Alistipes belonging to Rikenellaceae and the genus Lachnospira compared to men at low risk of PCa and those who are PCa-free (80). These bacterial taxa are associated with SCFA content in the stool and are SCFA-producing bacteria (81)(82)(83)(84)(85)(86).…”