Alterations of gut microbiota composition in post-finasteride patients: a pilot study. Melcangi, 2020

Science PFS Research
#1

FULL TEXT: https://link.springer.com/article/10.1007/s40618-020-01424-0

  • [Published: 19 September 2020]

Alterations of gut microbiota composition in post-finasteride patients: a pilot study

  • [F. Borgo]
  • [A. D. Macandog]
  • [R. C. Melcangi]

[ Journal of Endocrinological Investigation ]

Abstract

Purpose

Post-finasteride syndrome (PFS) has been reported in a subset of patients treated with finasteride (an inhibitor of the enzyme 5alpha-reductase) for androgenetic alopecia. These patients showed, despite the suspension of the treatment, a variety of persistent symptoms, like sexual dysfunction and cognitive and psychological disorders, including depression. A growing body of literature highlights the relevance of the gut microbiota-brain axis in human health and disease. For instance, alterations in gut microbiota composition have been reported in patients with major depressive disorder. Therefore, we have here analyzed the gut microbiota composition in PFS patients in comparison with a healthy cohort.

Methods

Fecal microbiota of 23 PFS patients was analyzed by 16S rRNA gene sequencing and compared with that reported in ten healthy male subjects.

Results

Sexual dysfunction, psychological and cognitive complaints, muscular problems, and physical alterations symptoms were reported in more than half of the PFS patients at the moment of sample collection. The quality sequence check revealed a low library depth for two fecal samples. Therefore, the gut microbiota analyses were conducted on 21 patients. The α-diversity was significantly lower in PFS group, showing a reduction of richness and diversity of gut microbiota structure. Moreover, when visualizing β-diversity, a clustering effect was found in the gut microbiota of a subset of PFS subjects, which was also characterized by a reduction in Faecalibacterium spp. and Ruminococcaceae UCG-005, while Alloprevotella and Odoribacter spp were increased compared to healthy control.

Conclusion

Gut microbiota population is altered in PFS patients, suggesting that it might represent a diagnostic marker and a possible therapeutic target for this syndrome.

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#2

Thank you for sharing this.
I always wonder why these patients dont come and say that they are going to be a part of a pilot study.
Anyway. This finding; should it be considered as the result of PFS or the cause of PFS. I think it is more likely to be the result.

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#3

In my opinion this is the result too. I mean wasn’t there were some people who went for fecal transplant?

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#4

Is there a way to gain access to the test form he ordered for this stool test? I’d like to take the test myself and see how messed up my gut is based on the things he had tested. My stools and digestion in general are so messed up.

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#5

The study itself states it is likely the result of alteration of androgens and nuerosteroid levels changing due to PFS.

Melcangi has put out 5 or so studies in the time that Baylor has put out 1. Its too bad he isn’t focusing on AR, but he is doing most of this without our funding. We are lucky to have him on our side!

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#6

This is very interesting, but I believe it’s more the result of PFS rather than the cause. Many people develop gut issues when PFS sets in. This doesn’t surprise me at all.

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#7

I had less smelly stools and body odor at the worst of PFS, this doesn’t surprise me at all.

#8

My shit smelled like ammonia so strong it would burn your eyes…Smelled like someone dumped a gallon of clorox bleach in the toilet…Now for along time that has stopped and just smells like a horrid rotting dead animal or something…

3 Likes
#9

Yea and don’t expect this one (baylor) anytime soon either…Khera told me they are still analyzing the data…They been analyzing for years.

Would not surprise me if its around the 10 year mark since the study was announced (2013) before the findings are published.

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#10

haha your shit burned your eyes? what did you do stare at it for 10 minutes? :joy:

1 Like
#11

Do any mods/admins like @axolotl or @awor have any input to offer on the significance of this study? I understand that Melcangi has drawn his own hypotheses, but I was wondering if our thought leaders had anything to offer or infer from this.

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#12

Seems to me that a lot of bacteria that produce butyrate are decreased. This was also evident in the rat models. However, while there is a healthy control group, it wouldn’t hurt to have a control who is using or used finasteride and didn’t get post finasteride syndrome. If the bacteria would decrease in that group as well, it wouldn’t be a marker of anything. If it didn’t, that’s another story.

4 Likes
#13

I’m Italian. I asked me why the community don’t give a money for the study at Roberto melcangi? Why?For the next study of allopregnanolone I give my money at Italian communities…but the other peaple have a this problem why waiting? The time go fast and the best yeas ago… I don’t understand this… If Roberto search 1 thing if a not a golden cure but for this community is important for a quality of life… Why don’t belive I Roberto melcangi? And waintg Baylor study for all rest of the life? Why?

8 Likes
#14

Im just going to give a rundown of this again real quick. This would probably be an even more advanced way of looking at whats going on in the stool. Again though im not sure if this would tell the whole story.
They talk about the gut microbiome (most studied), what about?
The eye microbiome?
Sinus microbiome?
lung microbiome?
oral microbiome?
Prostate microbiome?
Testicular microbiome?
Skin microbiome?
Is there a brain microbiome?
Do you want everything thats in your shits in these places as well?
Not sure, but you could possibly look at the gut having a systemic impact.

Mayo Clinic expands collaboration with Viome to include heart disease, obesity and insomnia

Why Viome’s Technology is Superior – Understanding Metatranscriptomic Analysis

  • Next on the scene was 16S rRNA gene sequencing. This technology, sequences the DNA of one of the thousands of bacterial genes and so it can only identify bacteria at the genus level and certainly can’t differentiate between active and inactive microbes. It is also unable to identify viruses or eukaryotes, since these organisms do not contain a 16S gene.3

Next came metagenomic sequencing a.k.a whole shotgun sequencing of the microbiome. This technology can detect microorganisms at species or strain level, as well as eukaryotes and DNA viruses only. It can also see what genes are present.

Finally, Viome’s
Metatranscriptomic analysis allows us to see it all. This includes bacteria, archaea, eukaryotes, DNA and RNA viruses and what genes they are expressing. In other words we can see who everyone is, and what everyone in the microbiome is doing.

Ignore all their marketing, the technology is whats most important. Probably the most advanced way to look at this atm.

I would also say their study is not definitive of anything, but at least we would know who to get in touch with if anyone of us ends up being right about some things or in figuring something out. Ive already looked at some of what they mention. GABA producing bifido etc.
bifido might also be capable of promoting inflammation though so idk.

I’ll also add that Viome has technology that they are currently not utilizing at the moment, because it has to go through an approval process based on their certification.
Right now you would only be comparing active microbes amongst us that are either there or not.
(What they are not showing yet, metabolites and gene expression. https://www.viome.com/test-your-microbiome)

Example, the italian study mentions decreased bifido, well what bifido?
This was the only bifido found in my stool, heard of this one?
Bifidobacterium pseudocatenulatum.
They can detect the probiotic Align, so a person could literally take this supplement for a period of time and then see if it shows up in the stool after x amount of days/months.

This isnt an endorsement of Viome but maybe a statistic to at least check and compare a few.

Viome is the world’s first company to offer CLIA-certified RNA sequencing technology. Your microbiome analysis is performed in a United States laboratory that is certified to meet CLIA standards—the Clinical Laboratory Improvement Amendments of 1988. A CLIA-certified lab must meet certain quality standards and ensures the accuracy and reliability of your results.

About CLIA | CDC

www.cdc.gov › clia › law-regulations
](https://www.cdc.gov/clia/law-regulations.html)

In general terms, the CLIA regulations establish quality standards for laboratory testing performed on specimens from humans, such as blood, body fluid and tissue, for the purpose of diagnosis, prevention, or treatment of disease, or assessment of health.

#15

I’d like EVERYONE reading this message to know that focusing my efforts on modulating gut microbiome has been the most influential factor in my years long journey to sustained recovery. EVERYTHING else was just a temporary fix for me. Godspeed

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#16

You can get microbiome testing from Ubiome, Viome, ThryveInside. Though keep in mind testing isn’t 100% reliable. It helps draw some conclusions.

1 Like
#17

@Preoccupato, @orthogs

First, I can’t speak for the rest of the staff. The following is only my opinion/view of the Melcagni/Milan research into PFS.

The idea that a comparison of rats in their pre vs post finasteride condition represents PFS is as absurd as feeding rats a dopamine receptor blocker and claiming their post-drug state represents tardive dyskinesia. (another somewhat uncommon and long-term post-drug condition that has been suggested to be epigenetically driven). I’m angry that up to $2,000 that I donated (under the impression it was ALL going toward studying enzyme expression/activity in CFS of PFS) to study a health condition I believe is the same, or similar, to mine was wasted on this nonsense. IMO, it’s garbage that should be left for scientists observing the common effects of finasteride, not PFS.

@anacleta, is it correct that Melcagni and the Milan team will be performing a similar rat study to investigate what they consider to be PSSD, rather than testing neurosteroid levels in the CSF of PSSD patients? I feel sorry for your patient community if so. It would be too easy to directly investigate a potential link between PFS and PSSD and potential explanation for PSSD symptoms.

Half of PFS patients were found to have hypermethylated 5-ar-II gene promoters. Why are other enzymes, an underlying mechanism to explain this, or receptors for these various neurosteroids not being investigated instead of microbiome status of the gut? Are there grants available to supplement microbiome research, or was this approach decided on a whim?
Perhaps the last study can be followed up by determining what in the environment of the microbiome has changed.

Bottom line, I refuse to exert any effort to support research that doesn’t make common sense to me, taps scarce resources to examine tangential aspects of any post-drug syndrome, or makes bold assumptions of a proper rodent model of a poorly understood disease. I also believe that any investigator willing to take money from a patient community owes it to the patient community to clearly justify their research and should be held accountable to follow a pre-determined research protocol in a pre-defined time frame. Otherwise, the awful status quo of post-drug research will remain intact.

So, some anonymous idiot who has read some biology books thinks Melcagni’s method of investigating PFS sucks and isn’t worth his time or money. That’s about all these statements are worth and the rest of the staff might have a different viewpoint. Someone asked why there isn’t more support for the Melcagni/Milan research and this is my personal reason that may be shared by others.

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#18

Idk, doesnt make bad sense to me. i’ve posted this and quite a few more like it across all three drugs, a possible common denominator. I think you would have to find alot more correlations then just a stool test though.

A new study in mice led by UCLA biologists strongly suggests that serotonin and drugs that target serotonin, such as anti-depressants, can have a major effect on the gut’s microbiota
https://neurosciencenews.com/ssri-serotonin-microbiome-14877/#:~:text=How%20serotonin%20and%20a%20popular%20anti-depressant%20affect%20the%20gut’s%20microbiota,-FeaturedNeurosciencePsychology&text=Summary%3A%20Serotonin%20and%20SSRIs%20like,lower%20levels%20in%20mouse%20models.

The effects of systemic isotretinoin and antibiotic therapy on the microbial floras in patients with acne vulgaris

Conclusions: Systemic isotretinoin and antibiotic treatments in acne patients precisely caused variations in the microbial floras of several sites of the body, while isotretinoin was commonly more responsible than antibiotics. Knowing that alterations in the microbial colonization of the flora regions may preceede infectious disease and bacterial resistance, treatment options and follow-up procedures in acne vulgaris should be carefully determined to reduce the risk of destruction of the microbial flora

All of this type of research is still in its infancy as they like to say.
Telling microbe numbers like reduced/increased isnt enough, eventually I think it will go much beyond that.

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#19

Yeah but who we have besides Melcangi’s team? We can wait for a Baylor study but tell me who belive that it will bring something important?

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#20

This is a good finding but how they can say this is the root cause? It looks like a side effect of the unknown root cause of PFS to me. Also it is very sad at the same time. That we had this solution in our hands but nobody gained acsess to it because nobody cares for us.

People have been suffering from this disease for 20 god damn years and i believe, if some millionaire wanted, the root cause of PFS could be found and treated in matter of months.

We send rockets to space. This god damn disease must be ice on the cake if the elite wanted to solve it. So, what we should do for this gut issue?

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