Bifidobacteria: friendly players in immune regulation

General Discussion
#1

I thought this was a good simple summary of one possible aspect of disease progression.

Bifidobacteria and subsets of dendritic cells: friendly players in immune regulation!

The mammalian gastrointestinal tract harbours a vast number of bacterial residents, recently referred to as the microbiota, which are instrumental in supporting energy metabolism and immune function of the host. A large number of studies have highlighted the fact that certain (pathogenic) micro-organisms can be harmful to the health of their host, while more recently an increasing number of papers have attributed direct beneficial health effects to the gut microbial community. As these bacteria encode 100 times more genes than present in the human genome, the partnership of the host with its microbiota constitute a ā€˜superorganismā€™.1 Homoeostasis in this superorganism is sustained through an optimal cohabitation of the host with this microbiota, keeping the balance between commensals and pathogens, but also between proinflammatory and regulatory responses. The composition of the gut microbiota has indeed been shown to be an important determinant of Th17:Treg balance and may thus influence intestinal immunity and tolerance.2 Disturbing alterations in the composition of the microbiota (a process known as dysbiosis) will compromise such homoeostasis and promote the development of various inflammatory disorders, such as inflammatory bowel disease. An in-depth understanding of the mechanisms underlying hostā€“symbiont relationships will be pivotal for the development of new therapeutic or prophylactic interventions targeting the intestinal microbiota.

#2

Iā€™ve read somewhere That Bifidus strands were supposed to make up 90% of the gutā€™s biome (if I remember correctly), Acidophilus 5% (theyā€™re supposed to help Bifidus by making the guts more acid which kills and reduces competing bacteria) and 5% other strands including a little bit of E-coli which are beneficialā€¦

From what I understand, the Acidophilus / Bifidus pair is primordial in maintaining a healthy guts balance.
I had a conversation with a guy on this forum saying that PFS sufferers donā€™t have Bifidus strands, nor E-coli which is really abnormal (if itā€™s true, and I canā€™t confirm). The conclusion to this discussion was that whatever caused our chemical imbalance also made our guts inhospitable to Bifidus and E-coli. We also concluded that if we donā€™t address this imbalance, taking Bifidus probiotic would not work as our guts are still inhospitable to them.

I also read many threads where they talk about guts imbalance and wanting to address it. I canā€™t remember anyone claiming being cured by taking probiotics only (some cases of autism or severe depression did get cured this way so it would not be so far fetched, but itā€™s not the case for PFS as far as Iā€™m aware of)

I believe our disease is above all an epigenetic disease and I adhere to the theory that our silenced androgen receptors result in a state of polyglutamic toxicity. Aside from the symptoms we know (high Glutamate / low GABA being a prime example), this toxicity could be responsible for making our guts inhospitable to Bifidus.

Iā€™ve been working with some degree of success IMO on repairing my epigenome using diet, exercise and some other tricks documented elsewhere on this forum.
I am now cultivating strands of Bifidus and Acidophilus in a jar using cucumbers or cabbage, and Iā€™m eating some live bacteria everyday. I do take Bifidus probiotics capsules on top of that. I have no proof they die or stay alive. Those who know me know Iā€™m not a get tested kind of guy. I judge by results, not by written words and numbers on a paper, no offense to those who do: you do you, I do me. My results so far is that mood is better and I have less stress, I wouldnā€™t call what I had anxiety at this point although I did have severe anxiety in the past (the kind I wanted to die to avoid).

Iā€™ll keep at it. So far the diet has by far yielded the best results, exercise and trick as well as NAD+ boosters (NMN) and bifidus supplements seems to help, but not as clearly as the diet.

In my case, there seems to be a particular set of events and circumstances that can trigger stronger symptoms, or diminish them in their absence. In my case again, there appear to be psychological triggers or inhibitors that influence the severity of symptoms. Before anyone jump at my throat, I will point out that psychological stress is one of the causes of epigenetic changes, in some case enough to cause diseases very similar to ours. A girl whose mother in law was stressing her out so much developed the same kind of symptoms we have. A bad boss, a stressful ā€œloveā€ relationship etcā€¦ can all cause adverse epigenetic changes. At this point, itā€™s a theory for me, not an affirmation.

However, to test it out, I will try to avoid the recognized psychological triggers and see if it does something.

Bottom line: the disease is most certainly epigenetic, the epigenetic changes may have caused guts biome imbalances but itā€™s not clear if we can address those before addressing the epigenetic causes, which are undoubtedly chemical (fin or other) and quite possibly environmental although thereā€™s not enough evidence to conclude environmental causes are factual.

Nonetheless, Iā€™m working on those three aspects: my epigenome first, than my guts biome and my psychological state.

Iā€™ll keep you guys posted on the results as they come.

I wish you all the best.

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#3

Again id maybe take the (s) off of probiotics.
How ive been looking at this are select strains that may perform select metabolic functions.
Retinoic Acid metabolism for example, thats something that makes sense to me.

Looking at possible microbial involvement in PFS, lets pretend its a vitamin deficiency.
Iā€™ll use b12 as an example, which can cause severe symptoms if left untreated.
Would you treat this b12 deficiency by taking a multivitamin?

Whats really on the market when it comes to viable almost drug like probiotics?
Whats popular or well researched?
Thats a pretty short list. Iā€™ll add to this when I get a chance.

Most researched commercially available bifido based probiotics
Bifido longum 35624 (isolated directly through biopsy)
Bifido longum bb536 (isolated from infant feces?)
Bifidobacterium animalis subsp. lactis bb12 (dairy strain)
Evivoā€™s B. infantis EVC001 (Bill Gates backed infant type strain)

and thats about it for well researched commercially available bifido strains.
Pretty short list.

#4

Still looking at this strain,

Bifidobacterium longum ssp. longum 35624, previously classified as Bifidobacterium longum ssp. infantis 35624, classified as Bifidobacterium infantis 35624 before that and still marketed as such. It is sold under the brand name Align in the US and Canada and Alflorex in Ireland, the UK and other European countries. It is patented. This strain was isolated directly from the epithelium of the terminal ileum of a healthy human subject

Seeing where retinol may accumulate.
This is something I have mentioned, the vitamin a might already be there.
Im looking at possible lack of synthesis from absent bacteria or dysbiosis.

Retinyl esters (RE), all-trans retinol (ROL), and all-trans RA
were extracted from the duodenum, jejunum, and ileum
mice had comparable amounts of REs, indicating that the RA
deficit is not due to a lack of vitamin A absorption or storage

Restoring Retinoic Acid Attenuates Intestinal Inflammation


You could maybe take out ā€œintestinalā€ and this could still be a true statement.
RA plays a major role in skin ā€œdysbiosisā€ or homeostasis as well.
Hydration, color, thickness, fine lines and wrinkles, wound repair.

I am just going to say right now, I think this could go in the other direction as well. Commensal bacteria or lack of could cause RA deficiency as well as dysbiosis.

Commensal Bacteria Regulate Vitamin A Metabolism
and Storage

Animals cannot synthesize vitamin A de novo but obtain the
molecules as micronutrients from the diet. IECs are the main
cell type responsible for the uptake of dietary vitamin A (Chelstowska et al., 2016). After uptake by IECs, diet-derived vitamin
A or retinol can either be processed into retinyl esters or further
metabolized to RA by two sequential oxidation steps (Figure 1A). To assess whether gut bacteria play a role in modulating vitamin A metabolism, we quantified the amount of
various vitamin A metabolites (collectively called retinoids) in intestinal and extra-intestinal tissue of germ-free (GF) and conventional (CV) mice by liquid chromatography coupled to
mass spectrometry (LC-MS). We found that GF mouse small intestine had significantly higher concentration of active metabolite (RA) compared to small intestine of conventionally raised
mouse (Figure 1B). Concurrently, we observed lower concentration of precursor form (retinol) (Figure 1C) and storage form
(retinyl esters) (Figure 1D) in the intestinal tissue of GF mouse
compared to CV mouse. This indicates that gut bacteria suppressed the conversion of vitamin A into RA and promoted conversion into retinyl esters in the intestine. To assess whether
this accumulation of retinyl esters in the intestinal tissue of
CV mice corresponded with higher retinoids in liver where
80% of vitamin A of the whole body is stored, we also quantified retinoids in the liver. We detected significantly higher quantities of retinol and retinyl esters (Figures 1F and 1G) but not RA
in the liver of CV mice (Figure 1E), suggesting that the presence
of bacteria directed vitamin A metabolism away from RA synthesis in the intestinal tissue and toward vitamin A storage in
liver. These results imply that bacteria regulate the amount of
active metabolite of vitamin A locally

#5

ā€œA PROBIOTIC FORMULATIONā€

The invention relates to retinoic acid and immune regulation. Background
https://www.lens.org/lens/patent/109-792-552-784-343/fulltext

#6

How do you link the guts biome imbalances to someone getting completely blasted and PFS thereafter after a single pill ?

That is, someone takes a pill and starts feeling bad in the following hours or the next day, Has full blown PFS symptoms from that point on ?

Or someone like me, who on the other side took fin for almost 20 years and didnā€™t develop symptoms in the first 10-14 years ?

I donā€™t deny guts imbalance, Iā€™m just questioning the cause.

#7

Take the drugs out of the equation and just look at us as a group.
Youā€™ve had awor on here saying a couple pills of milk thistle made him far worse than Finasteride ever did.
Others have said similar from their original offending medication.
The disease is not drug specific.
Whats our defect?
Dont lean on the drugs too hard for answers.
Whats a recent topic on Fin?
Off target drug effects.
Meaning effects not specific to the drugs known mechanism of action.

#8

Hey, can you please talk about your diet which has helped you? I believe you guys about the gut microbiome idea. Do you avoid certain foods or try to take some specific foods for your gut health?

#9

Youā€™re making my point. The cause is epigenetic changes which can be triggered by a host of outside causes, some of them not even physical, most of them being chemicals. For many, the drug is long gone. What remains is the changes in the epigenome.

My point is if those changes in the epigenome donā€™t enable some strands of bacteria to survive in the guts, say Bifidus for example, then taking them as probitotic means throwing them in an inhospitable environment: they die.

Iā€™ll go even further from my experiments with bifidus: If I take lots of them combined with fibers to feed them on arrival, my insomnia gets worst. Maybe after the epigenetic changes, the body started reacting bad to Bifidus and made the environment inhospitable with the purpose of fighting them ? Speculation.

Nonetheless, if Awor got worst with milk thistle and we know the disease is epigenetic, canā€™t we deduct that milk thistle provoked epigenetic changes that made him worst ? Milk thistle is now all gone from his system. Iā€™m suggesting what remains is the epigenetic imbalances and gutā€™s biome is dysfunctional as a result of the current epigenomic state.

Are you taking the epigenome out of the equation and suggesting the guy that took a single pill of fin and had his mind blown out within 12 hours had this permanent condition because fin killed his guts biome ?
And he just need to reintroduce them in proper ratios and heā€™ll be fine ?

Because I have 12 years of taking fin to prove that fin does not kill bifidus.

Nonetheless, those are only opinions of mine. If, beyond theories and words, you actually have a personal anecdotal story of curing yourself with probiotics, by all mean share it with us !

I write this with no disrespect and no desire to antagonize you. Iā€™m merely feeding the conversation with different angles so we may better understand what ills us.

Please counter my arguments as you see fit. I donā€™t believe any of us has the complete picture so we need to exchange and challenge each otherā€™s theories.

#10

Yeah, you can say I avoid certain type of food. Like 99% of food. But I donā€™t do it to fix my guts (although there is evidence ketogenic diets do that) https://ketologic.com/article/keto-diet-gut-health/

Iā€™m following my version of the ketogenic diet with assorted tricks to fix the epigenome: that is, to activate sirtuin proteins that regulate the epigenome and the de-methylase enzyme.

I have anecdotal evidence itā€™s working. I had lots of large freckles covering my face after a bad sunburn 30 years ago. I read those are caused by epigenetic changes and my dermatologist told me they were permanent and no medicine or laser surgery could remove them (aside from cutting holes in my face).
The diet and associated tricks have removed 70% of them so far and itā€™s continually but slowly improving. That implies repair to the epigenome of those cells responsible for the freckles. Remember, when a cell reproduces, not only a copy of its DNA goes to the new cell, but a copy of its epigenome, hence the pernicious ā€œpermanencyā€ of our disease (if we take for granted itā€™s epigenetic in nature). Itā€™s only permanent IMHO if the epigenome is not fixed, spontaneously or on purpose.

Also almost all my pfs symptoms are gone. Sex is normal, brain is normal, motivation, joy of living, self-confidence etcā€¦ are all normal. My only remaining symptom is insomnia but with meds and herbs itā€™s under control. I sleep around 8 hours a day. Burning eyes and dry burning lips have gone away in the last 3 months.
Iā€™m not willing to try, but I think if I stopped the diet, meds and herbs I would get back many pfs symptoms but they would not be as severe as after I crashed. I have no way of proving this as I wonā€™t stop diet, meds and herbs.

Specifics:
Ketogenic diet is 70% of calories from fat, 26% from protein, 4% from carbs.
It is not a calorie restricted diet, you get all your calories (although calorie restriction and fasts are one of the tricks that produces sirtuins)
My version of the ketogenic diet is to make it an almost exclusively carnivore diet on top of having all the ketogenic attributes described above.
70% of calories are from animal fat, the great majority of which is Ghee.
26% of calories are from protein the great majority of which is beef, egg and mackerel (with high content of Omega 3 and GABA)
4% of calories are from carbs, thatā€™s less than 20gr coming from 2 tbsp of diluted cooked lentil puree,1 tbsp each of rolled oat and oat bran I take before sleep to lower cortisol, raise insulin and sleep better and a little bit of spinach (for taste I guess. No specific reasons to eat them).
Those 20 gr of carbs removes any carbs craving I would otherwise have.
Water is the only drink but minerals can be mixed in it (see below)

A typical day, 80% of the days:

Morning I take a bulletproof coffee with 2-3 tbsp of ghee, some coconut milk and zero carbs sweetener.

I may drink water in the afternoon.

I wait until 5 pm to eat 2 tbsp of lentil puree whipped with 5-7 tbsp of ghee, and egg, some low sodium salt (high potassium) and some lemon juice/ citric acid. Itā€™s like a Bearnaise sauce in which I add 140 gr of beef (any kind, usually fat ground beef) and 100 gr of steamed spinach. Drink: a glass of 0.5 gr magnesium chloride, 0.25 gr potassium chloride, apple vinegar and sparkling water.

No more liquids after 6 pm. If I get up to pee during the night, the night is over and the next day is ruined.

Before sleep, 1 tbsp of rolled oat, 1 tbsp of oat bran, 1 tbsp of ghee, 1 tsp of inusitol (vitamin B8), 2 1/3 tbsp of water. Microwave the mix 30 seconds, let it coold down, eat it right before sleep but at least 30 to 90 minutes after taking sleeping pills and herbs. Brush my teeth (carbs causes cavities right ?) and it usually knocks me out better than the meds and herbs. Iā€™ll sleep 5-10 minutes after closing my eyes, usually while trying to meditate. I have 8 hours sleep.

And thatā€™s it. One real meal a day, fat in the morning and a little carbs at night.

#11

The assorted sirtuin tricks are:

  • Exercise while glycogen depleted
  • Running or swimming and get out of breath (itā€™s actually getting out of breath that produces sirtuins)
  • Restricted caloric intake / intermittent fasting (mostly in my case) or fasting
  • Cold shower or bath
  • Hot saunas

Note that acumulated epigenetic damage is believed to be the main actor in aging. Not shortening telomeres although it contributes.
The diet and trick reverse both. I literally look younger than pre-crash, 5 years ago.

Iā€™m 53 years old:

IMG_20201227_141127
IMG_20201227_1411271934Ɨ1999 581 KB

And take a look at these. Remember freckles are the results of epigenetic damage, in my case a bad sunburn that had my face so swollen I couldnā€™t open my eyes.
I removed my face to remain anonymous but did not do any photoshop work on the skin shown.

2013:
Freckles 2013

2021:
Freckles 2021

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#12

I donā€™t really understand the gut obsession in this forum.

You can easily make some fermented foods at home and then eat them. You will find out within a few weeks whether this will help you or not.

It is like people on here have no idea how to run a basic experiment on themselves.

You need to write it down in a journal so you have a baseline. Make some sauerkraut. Then eat it daily. Then after a few weeks observe whether you are feeling better or not. Write that down also.

If you track it, you will prevent this endless cycle of speculation, in which nothing is ever started and nothing ever learned.

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#14

First of all im not saying im right about all of this, but I am predicting that I might be right about some of this.
Human commensal bifidobacteria are microaerotolerant microbes.
They are an anaerobic organism, meaning they may react negatively or die in the presence of oxygen.
You do not make some of these strains from sauerkraut or yogurt.
This is looking at select strains that may perform specific metabolic functions.

@Ozeph
As far as one pil or 20 or 200 or 2000, even a substance that could ultimately have a negative impact on health could stimulate the body to work against it. Even early anti-androgens could act as partial agonists to the AR receptor.
Look at ADT in prostate cancer as another example, it stimulates cancer cells to adapt.

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#15

I managed to ferment Bifidus which die in the presence of oxygen. You need a fermentation jar with a ā€œwater one way valveā€. Fist you ferment regular acidophilus strands like lacto bacillus. After a few days, CO2 has replaced and pushed out of the jar most of the oxygen. Then you can introduce Bifidus Animalis or other Bifidus. It works, but when you start eating it oxygen is introduced and you end up with some dead bifidus.

#16

I agree with that. Weā€™re actually saying the same thing. What you call the body working against it, I call epigenetic modifications (that makes the body work against it) for the better, or sometime the worst. By definition, the epigenome is the adaptation of our DNA to a changing environment. Itā€™s a way the body have to be more flexible than our static DNA. The epigenome enhances or inhibits parts of our DNA to better adapt. Our problem is the best adaptation our body found to an overly aggressive environment is a grotesquely imbalanced and fluctuating state. Very uncomfortable but better than dying I guess !

The question remains how do we reverse it. If DNA is a memory, the epigenome has no memory of its prior states at all.
Dr. David Sinclair has drugs that can erase all epigenetic modification (and I mean all of them). If we were to take that, we would express only and purely our DNA as it was at conception. All the beneficial adjustments made since would have been forgotten, but so would PFS (and alcoholism or heroin addictionā€¦ Itā€™s quite something). By the way, it is a cure IMO but is it a desirable one ? Can we survive it ?

#17

I donā€™t understand any endeavors on this forum that doesnā€™t have anything to do with the epigenome. Studies have been made, the people managing this forum agrees, (unless Iā€™m mistaking): itā€™s an epigenetic disease.

The next step IMO is to find out what is the epigenome and what can be done to fix it. Unless the causes of the epigenetic changes are still present, all that remains is a dysfunctional epigenome (that messes up with proper protein creation, the basis of all hormones, enzymes, neurotransmitters etcā€¦)

If the causes are still present, then the next step is to find out what and where they are, and what can be done to remove them. After that the epigenome can be addressed.

It really puzzles me. I have pictures of what epigenetic repair from damage caused by a severe sunburn would look like. Something some dermatologists would deem impossible. Proof of removing those epigenetic damage (well, as far as I understand it. I actually didnā€™t look at my histones with an electronic microscope to see if theyā€™re rolled up properly or if methyl groups are not blocking genes anymore). I donā€™t understand why people are not more interested.

So you see, that makes two of us not understanding. Doesnā€™t matter though. weā€™re not important and even if we were people are free to believe what they will. So Iā€™m working on what I can change (myself) and acknowledging what I canā€™t (others) and not wasting too much energy on what I canā€™t change. Plus, not understanding something is not a big deal unless the lack of understanding can cause harm, which is clearly not the case here.

The catch though is this one: Does what we think we understand really relate to reality or is it just delusions ?

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#18

Im looking at bacteria as a possible source of RA which could also convert dietary vit a (retinol) to RA. The question would be could this have an impact on systemic levels of RA?

Commensal bacteria generate a variety of metabolites through either direct synthesis or breakdown of dietary components that can be absorbed in the intestine and potentially travel systemically (Matsumoto et al., 2018; Wikoff et al., 2009). For example, well-characterized bacterial-derived short-chain fatty acids that are produced by bacteria in the intestine can regulate local cells as well as distant tissues

Commensal bacterial-derived retinoic acid primes host defense

Commensal bacteria provide a direct source of retinoic acid that improves host defense

data collectively reveal RA as an unexpected microbiota-derived metabolite that primes innate intestinal defense and suggests that pre- and probiotic approaches to elevate RA could prevent or combat pathogenic infection.

one example,
Bacillus cereus was described to express a bacterial aldehyde dehydrogenase enzyme ( bc ALDH1A1, KFL74159.1) that produces RA in vitro (Hong et al., 2016). Consistent with this work, we found that B. cereus produced RA when incubated with the vitamin A derivative, retinol

Now lets look at a bifido species, this would be strain dependent.
Interestingly, SFB, along with the well-known probiotic bacteria Bifidobacterium bifidum , encode bacterial ALDH enzymes that share these critical catalytic amino acid residues ( Figure 4C ). Furthermore, the predicted protein structures of ALDH enzymes from SFB and B. bifidum both exhibited marked overlap with bc ALDH1A1 ( Figure 4C ). Thus, to test whether these commensal bacterial strains generate RA in vivo , GF mice were colonized with SFB ( Figure S2B ) or B. bifidum ( Figure S2C ) and compared to GF controls. Mice colonized with ALDH-expressing SFB or B. bifidum demonstrated increased luminal RA relative to GF mice

Collectively, these results indicate that a subset of commensal bacterial populations can provide a direct source of RA in the intestine.

#19

Do you have any sense at all of when any epigenetic damage eraser ā€œdrugsā€ might conceivably become accessible?

#20

No idea. Dr. David Sinclair holds the patents.

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#21

I just bought this from Amazon:

They are ā€œmood boostingā€ gut bacteria. Iā€™ll tell the results if anyone is interested.