ADT & the gut microbiome.

[pjoshea13]

New study from Japan below [1].

Not good, & presumably worse for the more efficient Abiraterone than Lupron, say.

First, some terms:

(a) "The α- and ß-diversity of gut microbiota"

alpha diversity pertains to richness/variety

beta diversity is based on a before-after comparison

(b) "microbiota" versus "microbiome"

sometimes used interchangeably but not quite the same: microbiome refers to total genomes, biota to the microorganisms.

(c} "dysbiosis"

what happens in the gut while deprived of androgen.

***

A "24-week observational study investigated the relationship between testosterone levels and changes in gut microbiota in Japanese patients with prostate cancer undergoing ADT. Sequential faecal samples were collected 1 and 2 weeks before ADT, and 1, 4, 12, and 24 weeks after ADT."

"In total, 23 patients completed the study.

"The α- and ß-diversity of gut microbiota decreased significantly at 24 weeks after ADT ...

"Relative abundances of Proteobacteria, Gammaproteobacteria, Pseudomonadales, Pseudomonas, and concentrations of urea, lactate, butyrate, 2-hydroxyisobutyrate and S-adenosylmethionine changed significantly after ADT ...

"There was a significant positive correlation between the abundance of Proteobacteria, a known indicator of dysbiosis, and the concentration of lactate ..."

"The decline in testosterone levels resulted in detrimental changes in gut microbiota. This dysbiosis may contribute to an increase in frailty and an increased risk of adverse outcomes in patients with prostate cancer."

-Patrick

[1] pubmed.ncbi.nlm.nih.gov/354...

Prostate Cancer Prostatic Dis

. 2022 Apr 13. doi: 10.1038/s41391-022-00536-3. Online ahead of print.

Gut environment changes due to androgen deprivation therapy in patients with prostate cancer

Akimasa Kure 1 2 3 , Tomoya Tsukimi 2 4 , Chiharu Ishii 2 4 , Wanping Aw 2 4 , Nozomu Obana 3 , Gaku Nakato 5 , Akiyoshi Hirayama 2 4 , Haruna Kawano 1 , Toshiyuki China 1 , Fumitaka Shimizu 1 , Masayoshi Nagata 1 , Shinji Isotani 1 , Satoru Muto 1 6 , Shigeo Horie 7 8 , Shinji Fukuda 9 10 11 12

Affiliations collapse

Affiliations

1 Department of Urology, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.

2 Institute for Advanced Biosciences, Keio University, 246-2 Mizukami, Kakuganji, Tsuruoka, Yamagata, 997-0052, Japan.

3 Transborder Medical Research Centre, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.

4 Systems Biology Programme, Graduate School of Media and Governance, Keio University, 5322 Endo, Fujisawa, Kanagawa, 252-0882, Japan.

5 Kanagawa Institute of Industrial Science and Technology, Life Science & Environment Research Centre (LiSE) 4th floor Room 4C-6, 3-25-13 Tonomachi, Kawasaki-ku, Kawasaki-shi, Kanagawa, 210-0821, Japan.

6 Department of Advanced Informatics for Genetic Diseases, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.

7 Department of Urology, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan. [e-mail].

8 Department of Advanced Informatics for Genetic Diseases, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan. [e-mail].

9 Institute for Advanced Biosciences, Keio University, 246-2 Mizukami, Kakuganji, Tsuruoka, Yamagata, 997-0052, Japan. [e-mail].

10 Transborder Medical Research Centre, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan. [e-mail].

11 Systems Biology Programme, Graduate School of Media and Governance, Keio University, 5322 Endo, Fujisawa, Kanagawa, 252-0882, Japan. [e-mail].

12 Kanagawa Institute of Industrial Science and Technology, Life Science & Environment Research Centre (LiSE) 4th floor Room 4C-6, 3-25-13 Tonomachi, Kawasaki-ku, Kawasaki-shi, Kanagawa, 210-0821, Japan. [e-mail].

PMID: 35418210 DOI: 10.1038/s41391-022-00536-3

Abstract

Background: It is estimated that by 2040 there will be 1,017,712 new cases of prostate cancer worldwide. Androgen deprivation therapy (ADT) is widely used as a treatment option for all disease stages. ADT, and the resulting decline in androgen levels, may indirectly affect gut microbiota. Factors affecting gut microbiota are wide-ranging; however, literature is scarce on the effects of ADT on gut microbiota and metabolome profiles in patients with prostate cancer.

Methods: To study the changes of gut microbiome by ADT, this 24-week observational study investigated the relationship between testosterone levels and changes in gut microbiota in Japanese patients with prostate cancer undergoing ADT. Sequential faecal samples were collected 1 and 2 weeks before ADT, and 1, 4, 12, and 24 weeks after ADT. Blood samples were collected at almost the same times. Bacterial 16 S rRNA gene-based microbiome analyses and capillary electrophoresis-time-of-flight mass spectrometry-based metabolome analyses were performed.

Results: In total, 23 patients completed the study. The α- and ß-diversity of gut microbiota decreased significantly at 24 weeks after ADT (p = 0.017, p < 0.001, respectively). Relative abundances of Proteobacteria, Gammaproteobacteria, Pseudomonadales, Pseudomonas, and concentrations of urea, lactate, butyrate, 2-hydroxyisobutyrate and S-adenosylmethionine changed significantly after ADT (p < 0.05). There was a significant positive correlation between the abundance of Proteobacteria, a known indicator of dysbiosis, and the concentration of lactate (R = 0.49, p < 0.01).

Conclusions: The decline in testosterone levels resulted in detrimental changes in gut microbiota. This dysbiosis may contribute to an increase in frailty and an increased risk of adverse outcomes in patients with prostate cancer.

© 2022. The Author(s), under exclusive licence to Springer Nature Limited.

[Graham49]

Perhaps people on ADT should work harder to keep good diversity of microbiota, e.g. probiotics, prebiotics and diversity of plant foods?

[Hidden]

Contrary to what I would have expected it was found that increases in (speculative) PCa therapeutic gut bacteria were noted in men who took Zytiga.

Abiraterone acetate preferentially enriches for the gut commensal Akkermansia muciniphila in castrate-resistant prostate cancer patients | Nature Communications

nature.com/articles/s41467-...

[PhilipSZacarias in reply to Hidden]

Bang on! Cheers, Phil

[pjoshea13 in reply to PhilipSZacarias]

The Japanese study refers to "ADT". I don't care for the term since it is now used in most papers to mean "classic" ADT. I don't know if that was the case here.

The study followed the men for 24 weeks. Typically, not long enough for CRPC. 24 weeks was long enough to establish that 'ADT' causes dysbiosis, but I doubt that was the end of the story.

Incidentally, wasn't there a study that discovered that the microbiome of some CRPC men was manufacturing androgen?

Best, -Patrick

[Hidden in reply to pjoshea13]

I think there are a couple of them. sperlingprostatecenter.com/...

[PhilipSZacarias in reply to pjoshea13]

That is correct and abiraterone inhibiting the production of the androgens. Cheers, Phil

[Spyder54]

Thank you again Patrick,It’s probably true for many of us. Certainly more than the 23 patients who completed the study.

So…what do we do to improve the Microbiota in the gut?? Probiotics ?

Mike

[pjoshea13 in reply to Spyder54]

Mike,

"... what do we do to improve the Microbiota in the gut?"

Testosterone [T]! LOL

When I was on repeated cycles of 3 months castration followed by 3 months of high-normal T (my PCa golden years), I suppose there was a reversal during the latter half. Perhaps only partial - & I probably should have been using pro- & pre- biotics throughout.

Real answer: It wouldn't hurt to use probiotics (& inulin, a prebiotic) IMO. The Japanese lab should repeat the study with a probiotic intervention. Perhaps they could throw in some Akkermansia?

-Patrick

[Hidden in reply to Spyder54]

Akkermansia might help with PCa. Hasn't been proven though.

I have had my gut microbiota tested and supposedly it is excellent for cancer therapeutics. I'm not sure how much stock to put in that and, at this time, I don't try to change what nature is doing in my gut.

19. Akkermansia is speculated to be a PCa beneficial gut bacteria: Strategies to promote abundance of Akkermansia muciniphila, an emerging probiotic in the gut, evidence from dietary intervention studies - PMC

ncbi.nlm.nih.gov/pmc/articl...

20. Akkermansia is speculated to be a PCa beneficial gut bacteria: Abiraterone acetate preferentially enriches for the gut commensal Akkermansia muciniphila in castrate-resistant prostate cancer patients | Nature Communications

nature.com/articles/s41467-...

My MO and I think that metformin and Zytiga are beneficial for me so I take both of them. I don't have a baseline measurement of Akkermansia and therefore don't know if it was increased by metformin or Zytiga. But it's high for now.

Akkermansia is in the Verrucomicrobiaceae family. My results are about 20 times the average.

[SteveTheJ]

Interesting. I started taking kefir every morning. I don't know if it's helping or not but I'm continuing to take it.

[Farmhand]

aGood probiotic : I use Klaire Labs….Expensive but worthwhile

[Currumpaw]

Hey pjoshea13,

Some Green Vibrance and a sauerkraut from the refrigerated section of Whole Foods is usually all I take. The sauerkraut people also make a nice kimchi.

Be careful of "too much". Good things can become bad things. I have a neighbor, a nurse, that overdid pro and prebiotics. Her doctor gave her a salve--hmm--hmm. She mentioned probiotics. I asked how much. I explained that she should not take any more of the two types--she was covering the bases. Within a day or so she said that she was 'back to normal".

I know you have it figured out pjoshea13. For those that are new to this pro and prebiotic what happened to my neighbor is a good read with a chuckle thrown in.

My friend who manages a Vitamin Shoppe has a customer that had reflux that his doc medicated him for. Also blood pressure meds. His prescribed meds and the supps on the shelf weren't helping his reflux. He walked into the VS smiling one day and told my friend that his reflux was gone and that his doctor told him he no longer needed blood pressure meds either. He had bought the sauerkraut at Whole Foods and eaten a forkful in the AM and the PM, when he got up and before he went to bed. His reflux stopped and his blood pressure became normal.

Currumpaw