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Gut Microbiota-Derived Short-Chain Fatty Acids Promote Prostate Cancer Growth via IGF1 Signaling. | LitMetric

AI Article Synopsis

  • Excessive consumption of animal fat is linked to obesity and increased risk of prostate cancer, prompting research into the gut microbiota's role in this connection.
  • Using a prostate cancer model, researchers found that antibiotics altered gut microbiota composition, inhibited cancer cell growth, and reduced insulin-like growth factor-1 (IGF1) levels, which are crucial for tumor proliferation.
  • The study reveals that gut microbes, through short-chain fatty acids, can regulate IGF1 production, promoting prostate cancer cell growth, suggesting that modifying gut microbiota may help in preventing and treating prostate cancer.

Article Abstract

Excessive intake of animal fat and resultant obesity are major risk factors for prostate cancer. Because the composition of the gut microbiota is known to change with dietary composition and body type, we used prostate-specific knockout mice as a prostate cancer model to investigate whether there is a gut microbiota-mediated connection between animal fat intake and prostate cancer. Oral administration of an antibiotic mixture (Abx) in prostate cancer-bearing mice fed a high-fat diet containing a large proportion of lard drastically altered the composition of the gut microbiota including and , inhibited prostate cancer cell proliferation, and reduced prostate expression and circulating insulin-like growth factor-1 (IGF1) levels. In prostate cancer tissue, MAPK and PI3K activities, both downstream of the IGF1 receptor, were suppressed by Abx administration. IGF1 directly promoted the proliferation of prostate cancer cell lines DU145 and 22Rv1 . Abx administration also reduced fecal levels of short-chain fatty acids (SCFA) produced by intestinal bacteria. Supplementation with SCFAs promoted tumor growth by increasing IGF1 levels. In humans, IGF1 was found to be highly expressed in prostate cancer tissue from obese patients. In conclusion, IGF1 production stimulated by SCFAs from gut microbes influences the growth of prostate cancer via activating local prostate MAPK and PI3K signaling, indicating the existence of a gut microbiota-IGF1-prostate axis. Disrupting this axis by modulating the gut microbiota may aid in prostate cancer prevention and treatment. SIGNIFICANCE: These results suggest that intestinal bacteria, acting through short-chain fatty acids, regulate systemic and local prostate IGF1 in the host, which can promote proliferation of prostate cancer cells.

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Source
http://dx.doi.org/10.1158/0008-5472.CAN-20-4090DOI Listing

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