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

Science PFS Research
#67

You see how new some of this research is.
July 2018

Gram-Positive Bacterial Extracellular Vesicles and Their Impact on Health and Disease

Gram-Positive Bacterial EVs: an Upcoming Research Area

Although discovered 30 years later than their Gram-negative counterparts, Gram-positive bacterial extracellular vesicles (EVs) have been drawing more attention in recent years (Brown et al., 2015; Kim et al., 2015). Budding events of spherical particles and their release into the surrounding environment of the cells have been observed for a wide range of bacterial species belonging to the Gram-positive phyla Firmicutes and Actinobacteria

The expanding research field on Gram-positive EVs has so far revealed possible roles of EVs in bacterial ecology, physiology, and host–microbe interactions linked to health and disease depending on the bacterial species. In this light, EVs are also of potential value in medical and clinical applications. In this article we will provide new insights into the diversity, functionality, and possible applications of Gram-positive EVs

It could be a real simple concept,
Reinstall whats missing.

Adding to this from that same article, exactly like the patent describes.

Disease Diagnosis

The link between gut microbiota composition and human health or diseases is being revealed gradually in recent years (Marchesi et al., 2016; Yamashiro, 2017; Chelakkot et al., 2018). Studies show that EVs derived from the gut microbiota are distributed throughout the human body including the blood and urine, and they reflect the composition of the microbiota to a great extent (Kang et al., 2013; Jang et al., 2015; Yoo et al., 2016). This observation opens doors to novel methods of disease diagnosis or assessment. As an example, Lee et al. (2017) successfully developed a rapid, non-invasive assessment method on microbiota profiles in autism spectrum disorder patients by examining the 16S rRNA gene sequences in bacterial EVs isolated from urine samples. Since EV release is often the result of active metabolism in bacteria, EVs may form a better indication of the microbiota activities in the hosts than the bacterial populations themselves, and therefore provide more insights into the links between microbiota and the disease or health status of the hosts.

#68

I think there are a lot of clues to be learnt from victims’ symptoms (example below), experiments and similar diseases (e.g. SSRI-related). A gold mine of data waiting to be used by someone. I know my comment goes beyond the topic of gut biome, I hope that’s okay.

Some of the more interesting observations in myself:

  • Why does abstinence no longer drive sexual tension/libido?
  • Why does abstinence still lead to a stronger alertness/focus response in my brain to sexual stimuli, but not in my groin? Does that mean sexual problems are entirely in the groin, not the brain?
  • Why is the sensitivity to erogenous pleasure fairly well preserved in some parts of my penis (frenulum), but completely destroyed in others (the tip)? The very lower shaft is somewhere in between.
  • Evidence that lacking pleasure sensitivity is the root cause of our ED: stimulation of my tip no longer drives/maintains erections, while pressure/pull on my frenulum (area) still does. This is in line with claims that pleasure sensitivity decreases with age (in healthy men), as does ED.
  • Lacking pleasure sensitivity may also be the cause of our libido loss. Wikipedia says libido = dopamine hitting the nucleus accumbens in the brain. They do seem linked in my body (they are both up if I’m lucky to have morning wood, especially if my underwear has put pressure on areas of my penis that have some pleasure sensitivity left).
  • Why can’t I get an erection from either looking at porn or touching myself, but I can with the two combined?
  • Why do I still get (some) nocturnal erections and morning wood?
  • Why does morning wood give a temporary boost to erectile function, pleasure sensitivity, and libido, and why does it plummet after that, and disappear as the day goes on? Pre-PFS, these things would noticeably increase for me towards the evening.
  • What can we learn from the speed (hours!) at wich finasteride anesthesized my perineal region (loss of sense of erogenous aliveness in that region and in penis) and how fast it was reversed (hours!)? And from how fast it increased my refractionary period (days, possibly hours).

Imagine you’re a researcher trying to solve PFS but unaware of cues like these and others.

2 Likes
#69

Some good concepts here when it comes to possible treatment.

Fate, activity, and impact of ingested bacteria within the human gut microbiota

Most of the data discussed above derive from studies on fecal material, which is believed to be representative of the colonic microbial populations. Much less is known about the microbiome of the small intestine, due mainly to the fact that it is accessible only with invasive sampling. The small intestine is the primary site of food digestion, nutrient absorption, and metabolic signaling.

Ingested bacteria can cause major shifts in the composition of the microbiome of the small intestine, whereas alterations in the colon are mostly of limited extent.

It is noteworthy to mention, in the context of this review, that these communities are highly specialized in the utilization of simple dietary carbohydrates, much like food-fermenting bacteria (see below) – which may therefore compete for the same niche in the small intestine. Microbial population densities in the small intestine are much lower than in the colon, ranging from 104 cells per gram in the duodenum to 108 cells per gram in the terminal ileum. Hence, the consumption of a dose of 1010 (10 billion) ingested bacterial cells is predicted to induce a dramatic population shift that temporarily overcrowds resident communities and which is likely to impact the host’s immune and neuroendocrine functions

#70

Me too! I’ve had PFS for going on 2 years now and my digestion is still messed up.

#71

I also often have diarrhea as soon as I eat something other than meat/fish and vegetables. Cereals, milk, sugar…

#72

This was before PFS?
So are we looking for manly smelling shits?
Reminds me of a family guy episode.

Seriously though with what some have described, this is one test I mentioned.

Fecal pH provides a window into gut health

Elevated fecal pH is a sign of gut dysbiosis

pH, Stool

https://www.labcorp.com/tests/010991/ph-stool

#73

Just to follow up on this, it might be important to get some of this right if there were to be any chance for possible treatment.

What jumps out at me here is the presence of bifidobacteria in the small intestine.

Presence of two Lactobacillus and Bifidobacterium probiotic strains in the neonatal ileum
https://www.nature.com/articles/ismej200769

We are not aware of any previously published studies of the composition of the human neonatal ileal microbiota, owing to sampling difficulties. Indeed, it is worthwhile to emphasize that such cases are extremely rare but provide an almost unique opportunity to examine the human ileum at a very early stage of life. Few attempts have been made to isolate potential adherent probiotic bacteria directly from the human intestinal mucosa (the environment into which they are subsequently reintroduced and required to function). This study indicates the presence of two different probiotic strains ( L. paracasei NFBC 338 and B. animalis subsp. lactis Bb12) in the upper intestinal tract at an early stage of human life, which provides evidence for their ability to colonize the human small intestine.

Ingested bacteria can cause major shifts in the composition of the microbiome of the small intestine, whereas alterations in the colon are mostly of limited extent.

^Here could be a reason why “everything I take or ingest makes me worse.”
Further setbacks or worsening of PFS.
Realize this could be something as simple as a B-Vitamin

Cobalamin (Vitamin B12) Induced a Shift in Microbial Composition and Metabolic Activity in an in vitro Colon Simulation

#74

When looking at some type of possible bacterial therapy something to keep in mind is
Quorum sensing, what no drug, injection or supplement is capable of.

Bacteria sensing and responding to its environment through communication with other bacteria and the host.

In biology, quorum sensing is the ability to detect and to respond to cell population density by gene regulation. As one example, quorum sensing (QS) enables bacteria to restrict the expression of specific genes to the high cell densities at which the resulting phenotypes will be most beneficial.

Quorum sensing allows bacteria populations to communicate and coordinate group behaviour.

This could be both pathogenic and beneficial.
Im looking at this bacterial group right here it includes both Bifido and Propionibacterium.
Early colonizers.

Quorum Sensing: An Under-Explored Phenomenon in the Phylum Actinobacteria

A systematic and coordinated effort is required to screen and exploit the enormous potential that quorum sensing in the phylum Actinobacteria has to offer for human benefit.

#75

Eat special yoghurts (or go one or two steps further with pills, or diet). But this is honestly a silly topic wherever it crops up and whatever its reasons. Get a poo-transplant for all I care if you’re that into it. People obsessed with this kind of thing just have a special area of interest for psychological reasons. Otherwise it’s the most trivial topic one could imagine.

2 Likes
#76

I disagree.

5 Likes
#77

Its not p.acnes, but it is closely related.

Extracellular Vesicles Produced by the Probiotic Propionibacterium freudenreichii CIRM-BIA 129 Mitigate Inflammation by Modulating the NF-κB Pathway


Published online 2020 Jul 7

1 Like
#78

Ive been taking this off and on for some time now, and all I can say is man is this potent as an anti-inflammatory. Its something that builds up very quickly and I believe predicated on the scfa production of propionate.
Im not sure if its right though, a person would need to be very careful with the dosage because it doesnt take much.
Keep in mind most anti-inflammatories are also immunosuppressive and can be overdone or inappropriate.
This also might lower body temp or tissue temp which can be both good and bad as you got guys on here talking about taking cold showers, but others talking about having a cold penis.
The lower temp could be a defense mechanism to fight systemic inflammation and prevent tissue damage but it also reduces circulation.

Thermoregulation as a disease tolerance defense strategy

1 Like
#79

I dont know about this one though. You dabble enough with some of these potent probiotics and you’ll find the reason I stay on this subject.

I keep going back and forth between this p. freudenreichii and align or bifido longum 35624.
One is “ice” and one is “heat”
I think the generation of heat or circulation might be more important in pfs.

#80

What are your thoughts and or experiences with butyrate? It seems to have helped many and others not do much.

#81

Well butyrate is produced by bacteria, bacterial production is probably a rate limiter that prevents this scfa from becoming toxic.
Taking it separately as a supplement really doesnt make the most sense to me but idk, ive never tried it.
Id keep in mind there are other ways to go about increasing butyrate such as cross feeding from other bacteria.

Example, and theres quite a few like this.

Two Routes of Metabolic Cross-Feeding between Bifidobacterium adolescentis and Butyrate-Producing Anaerobes from the Human Gut

Lactate- and acetate-based cross-feeding interactions …

europepmc.org › abstract › med
](http://europepmc.org/abstract/med/27810444)

Cross - feeding interactions were studied between selected strains of lactobacilli and/or bifidobacteria and butyrate -producing colon bacteria that consume lactate …

Cross-feeding between Bifidobacteria and butyrate-producing …

www.researchgate.net › publication › 50935904_Cross-fe…
](https://www.researchgate.net/publication/50935904_Cross-feeding_between_Bifidobacteria_and_butyrate-producing_colon_bacteria_explains_bifdobacterial_competitiveness_butyrate_production_and_gas_production)

The conversion of lactate and acetate to butyrate ( crossfeeding of lactate) is a recognized nutritional interaction between lactate-and acetate -forming bacteria …

Probiotic Bifidobacterium longum alters gut luminal … - Nature

www.nature.com › scientific reports › articles
](https://www.nature.com/articles/srep13548)

Aug 28, 2015 — … a butyrate producer, was significantly higher in the BB536 -HGM group … with B. longum BB536 increased the fecal butyrate concentration.

^not to highlight bifido, it was just the quickest example. Not to say its whats right.

1 Like
#82

Thanks for your post.
I find butyrate is very good for cognitive issues.
But I feel the physical effects are a bit alarming and overwhelming and they come and go. Not sure if it is a sort of herx reaction or the activation of sleepy genes that make me look and feel sort of ill when its metabolizing. The after effects that linger are huge though.

#83

adding to this, cold induction. The example here is an ice bath. Also proper immune regulation consists of a balance between pro and anti-inflammatory responses.

“The concept of ice bath immersion after physical exercise is that the cold temperature will lead to a rapid-onset anti-inflammatory effect, as well as cause an intravascular fluid shift to reduce muscle swelling,” Dr. Nina Shapiro, professor at UCLA and author of HYPE: A Doctor’s Guide to Medical Myths, Exaggerated Claims and Bad Advice: How to Tell What’s Real and What’s Not , explains to Yahoo Life. “In addition, the goal is to enhance cardiac output and blood flow due to this fluid shift. It also acts to increase the release of adrenaline, which may, in turn, reduce physiologic fatigue.”

In other words, the initial jolt of the cold can essentially wake someone out of an exhausted state — a shock some practitioners may find enjoyable or therapeutic, though Shapiro notes that any mental health benefits are subjective. The cold temperature also slows the body down and lowers heart rate.

Dr. Taz Bhatia, an integrative medicine physician and wellness expert, agrees that ice baths can help athletes and fitness enthusiasts soothe sore muscles and inflammation post-workout. She adds that they can “play a role in training the vagus nerve, which helps to promote parasympathetic stimulation or the relaxation response, which is where healing occurs.”

1 Like
#84

There’s only one person who can help us address this microbial shift mentioned in the study with decades worth of experience and uses data banks to analyze microbiome and provide a specific protocol to restore balance.

I’ll post the recommendations when ever they are available. Stay hopeful!

8 Likes
#85

Im going to show this list here of what can be detected through Viome, its pretty impressive.
You see how easy and relatively cheap it could be to run our own pilot study. Fecal counts or whats active in the stool might not tell the whole story, but it might be better then nothing and worth checking. Viome has the most advanced technology to look at this atm, far beyond the Melcangi study.

My thought is whats going on in the small intestine might be most important, and what could be rapidly modifiable through diet or drugs like Finasteride. This to me makes much more sense as to how one pill could do so much ongoing damage.


Our method detects transcripts (RNAs) produced by the microbial community. We are able to see down to one in a million transcripts. We cannot detect microbes that contribute fewer than one in a 1,000,000 specific transcripts. In addition, Viome only sees active microbes in your gut. If other microbes are there, but are not active, we will not pick up their RNA. You can find your organisms in My Results > My Microbe Activity. Your organisms are in alphabetical order. You can see what category they are in with the letter next to it. P for probiotic, B for bacteria, A for Archaea, E for Eukaryote (Yeast including Candida, Fungus, Parasites if alive and active will be listed here) and V for Virus. However, since Viome is not diagnostic we only provide the scientific name and are unable to label them as pathogenic or parasitic.

1 Like
#86

I know who you talk，and I wish the day coming