The gut microbiota associated with high-Gleason PCa

[pjoshea13]

New Japanese study below [1].

Raises questions:

- what might be the role of pro- & pre- biotics in the management of PCa?

- how might circulating short-chain fatty acids affect progression?

-Patrick

"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 analysed the gut microbiota profiles of men with suspected PCa. 152 Japanese men undergoing prostate biopsies (96 with cancer and 56 without cancer) were included in the study and randomly divided into two cohorts: discovery cohort (114 samples) and 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{ceae}, all {short-chain fatty acid}-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 the carcinogenesis of PCa."

[1] Cancer Sci

. 2021 May 29. doi: 10.1111/cas.14998. Online ahead of print.

The gut microbiota associated with high-Gleason prostate cancer

Makoto Matsushita 1 , Kazutoshi Fujita 1 2 , Daisuke Motooka 3 , Koji Hatano 1 , Shota Fukae 4 , Norihiko Kawamura 5 , Eisuke Tomiyama 1 , Yujiro Hayashi 1 , Eri Banno 2 , Tetsuya Takao 5 , Shingo Takada 4 , Shinichi Yachida 6 , Hirotsugu Uemura 2 , Shota Nakamura 3 , Norio Nonomura 1

Affiliations collapse

Affiliations

1 Department of Urology, Osaka University, Graduate School of Medicine, Suita, Japan.

2 Department of Urology, Kindai University, Faculty of Medicine, Osakasayama, Japan.

3 Department of Infection Metagenomics, Research Institute for Microbial Diseases, Osaka University, Suita, Japan.

4 Department of Urology, Osaka Police Hospital, Osaka, Japan.

5 Department of Urology, Osaka General Medical Center, Osaka, Japan.

6 Department of Cancer Genome Informatics, Osaka University, Graduate School of Medicine, Suita, Japan.

PMID: 34051009 DOI: 10.1111/cas.14998

Free article

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 analysed the gut microbiota profiles of men with suspected PCa. 152 Japanese men undergoing prostate biopsies (96 with cancer and 56 without cancer) were included in the study and randomly divided into two cohorts: discovery cohort (114 samples) and 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 SCFAs-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 the carcinogenesis of PCa. Supporting Information Document S1: Mathematical structure of the FMPI.

Keywords: bacteria; biomarkers; gastrointestinal microbiome; metagenomics; prostate cancer.

This article is protected by copyright. All rights reserved.

[MateoBeach]

I too have been wondering about prebiotic and probiotic interventions to generate a favorable gut microbiome and what impact this could have on the progression of PC. I don’t know about the strength of the unfamiliar statistical approach to validate their index. Sounds sketchy. But this does suggest a connection to higher grade PC with a SCFA producing microbiome. Any thoughts on dietary or supplements to help? Thanks for posting it.

[pjoshea13 in reply to MateoBeach]

I'm rethinking inulin [1] as a prebiotic. I had been iterested in it a dozen or so years ago because it might result in a therapeutic level of butyrate [2].

"Triglycerides of butyric acid compose 3–4% of butter. When butter goes rancid, butyric acid is liberated from the glyceride by hydrolysis.[11] It is one of the fatty acid subgroup called short-chain fatty acids." (Wiki)

Ultimately, I was warned off by those who discusssed the unpredictability of the bacterial colonies promoted by inulin as a food source. Depends on the baseline populations, & perhaps it's essential to start inulin with probiotics. Others here will be more knowledgeable.

I was dealing with C-diff at the time & ditched the idea.

Some years later, I started using sodium butyrate.

I posted on the subject 5 years ago. Not much response back then [3].

Seems that much has been written since then. Here is the Abstract of the most recent paper [4]:

"Following cancer, cells in a particular tissue can no longer respond to the factors involved in controlling cell survival, differentiation, proliferation, and death. In recent years, it has been indicated that alterations in the gut microbiota components, intestinal epithelium, and host immune system are associated with cancer incidence. Also, it has been demonstrated that the short-chain fatty acids (SCFAs) generated by gut microbiota are vitally crucial in cell homeostasis as they contribute to the modulation of histone deacetylases (HDACs), resulting effected cell attachment, immune cell immigration, cytokine production, chemotaxis, and the programmed cell death. Therefore, the manipulation of SCFA levels in the intestinal tract by alterations in the microbiota structure can be potentially taken into consideration for cancer treatment/prevention. In the current study, we will explain the most recent findings on the detrimental or protective roles of SFCA (particularly butyrate, propionate, and acetate) in several cancers, including bladder, colon, breast, stomach, liver, lung, pancreas, and prostate cancers."

-Patrick

[1] en.wikipedia.org/wiki/Inulin

[2] en.wikipedia.org/wiki/Butyr...

[3] healthunlocked.com/advanced...

[4] pubmed.ncbi.nlm.nih.gov/339...

[kainasar in reply to pjoshea13]

Thank you for presenting study and some useful insights.I have used butyrate for radiation proctitis, and am fascinated to hear its use may be related to effects of SFCA's in other ways.

[Turt713171 in reply to pjoshea13]

Excellent information

[jdm3 in reply to MateoBeach]

For what it's worth, my naturopathic oncologist is big on gut biome and recommended this one a few times a week. Also, fermented foods - sauerkraut, kimchi, etc..

nhc.com/ther-biotic-complet...

[Hidden in reply to jdm3]

I'm a huge supporter of eating fermented foods like sauerkraut and kimchi...I read a paper that reported that fermented cabbage had more absorbable glusconates than regular cabbage..Either way, raw organic Sauerkraut and kimchi is an excellent addition to any diet.

[Purple-Bike in reply to jdm3]

I saw an analysis saying in excess of about 20 billion CFU daily was not likely to give any benefits in general. But your naturopath oncologist may know better, in the case of prostate cancer....

[jdm3 in reply to Purple-Bike]

Yeah. I don't know. She's very bright, well read, a Fellow of the American Board of Naturopathic Oncology, etc.. and early on (five years ago for me) recommended several of the supplements (D3, DIM, melatonin, MCP,.....) discussed in these forums as well as a probiotic. I actually stopped taking a probiotic last year because I read they were worthless and that for healthy gut just eat fermented foods. I just did a six-month check in with her last week and she asked if I was still taking the probiotic. Uh... no. She chided me and said again it was very important as a healthy gut microbiome is essential to our wellbeing.

[MateoBeach in reply to jdm3]

Thanks. That is a good tip. 👍

[CSHobie]

I was very interested in reading the article, but a quick search came up with this article, that says SCFAs are literally made by the so called healthy foods.

healthline.com/nutrition/sh...

Eating healthy, staying fit, keeping active, these are the things that bring PCa??? LOL.

[ck722]

Sauerkraut (home-made), yogurt, pickles and other ferments. No food with paragraph after paragraph of crazy chemicals that preserve freshness.

[Don_1213]

While the claim is made that "metabolites, short-chain fatty acids (SCFAs), promote cancer growth in prostate cancer (PCa) mouse models. " from this they make the jump to implying a causative effect of the same gut chemistry on human PCa. What isn't proven to my satisfaction is if the increased "metabolites and SCFAs" are the cause of PCa or the result of PCa. There does seem to be some correlation between PCa and these gut components, and that might be useful for diagnosis - but even that seems questionable since they stated: "we analysed the gut microbiota profiles of men with suspected PCa" - it seems the group they looked at were already at risk of PCa. A more valid study might take a larger number of men, not preselected by "suspected PCa" - just everyday men of perhaps a certain age - and then analyze their gut contents and test them for suspected PCa and see if there is a correlation.

I think drawing conclusions that certain probiotics are useful based on this study is really questionable, especially considering the number of contrary papers claiming that these same SCFAs are of value in fighting various health issues including some types of cancer.