Long complicated paper on gut microbi... - Advanced Prostate...

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Long complicated paper on gut microbiome and PCa, human and mouse studies.

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The gut microbiome-prostate cancer crosstalk is modulated by dietary polyunsaturated long-chain fatty acids

Nature Communications volume 15, Article number: 3431 (2024)

PMID: 38654015 PMCID: PMC11039720 DOI: 10.1038/s41467-024-45332-w

Some snippets from the paper:

”Hypercaloric diets, such as high-fat diet (HFD), stimulate the proliferation and activity of gut microbes, increase intestinal permeability, and are associated with bacteria-derived molecule leakage (endotoxemia) ultimately contributing to chronic inflammation12,13,14. ”

“In the present study we found a systematic reduction in gut microbiota diversity correlating with increasing PCa volume and aggressiveness in two distinct clinical scenarios of patients without ADT.”

“We also observed reduced gut microbiota diversity in the two distinct mouse models that grew the largest tumours, in particular those with loss of both Pten and Rb1, an alteration frequently observed in metastatic PCa patients28,29.”

“Transplantation to mice of human fecal microbiota (FMT) from patients with high tumour volume promoted the growth of the TRAMP-C2 tumours suggesting a bi-directional PCa and gut microbiota crosstalk. ”

“Clinical studies conducted on healthy individuals have reported different beneficial impacts of short-term omega-3 supplementation on the gut microbiota based on improved alpha diversity indexes or the transient augmentation of beneficial bacteria such as Bifidobacterium or Lactobacillus62,65,66. However, here we report the effect of omega-3 supplements on the gut microbiota of PCa patients and mouse models associated with potentially beneficial effect on cancer.”

“The gut microbiota was shown to affect the dynamic of circulating immune cells independently of immunotherapy treatments71,72, supporting that commensal bacteria can educate the immune system and modulate its anti-cancer activity. ”

“Overall, our studies revealed the existence of a crosstalk between PCa growth and the host gut microbes particularly those involved in the metabolism of LCFA. Supplementation with LCn3 resulted in a reduction of cancer growth in mouse models and reduction of upgrading in pre-prostatectomy patients associated with a reduction of gut Ruminococcaceae and fecal butyrate levels. It identifies one potential mechanism to explain the beneficial effect of diet rich in LCn3 in reducing the initial diagnosis and progression of PCa. This conceptual advance is important since targeting the microbiota via the diet is non-invasive, applicable to most cancer patients and could limit cancer progression in stages of the diseases where patients are not receiving other treatments.”

Notes

Long chain fatty acids (LCFA)

eicosapentaenoic acid monoacylglyceride (MAG-EPA)

docosahexaenoic acid monoglyceride (MAG-DHA)

Omega-3 polyunsaturated fatty acids from oily fish (long-chain omega-3 (LCn3)

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