#1

Hi! I’m very new to this and took my first 2mg of rapamycin today. I’m planning on a short term stint to delay menopause (43 year old female). Anyway, I’ve been extremely careful with my gut health over the years and I’m really apprehensive about negatively altering it with this drug. Has anyone tested their microbiome throughout the process? Have you noticed any negative effects? Thanks!

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#2

When you say you’ve been extremely careful with your gut health, what have you been doing? Do you have any testing or measurement you have done? I have not done any gut testing, but I make my own yogurt, kombucha, and sauerkraut, and I try to eat multiple servings of fermented food every day.

#3

I tested a few years ago and the results were poor-average. Since then I’ve eliminated all gums, emulsifiers, additives, etc. and eat fermented foods daily. I have not retested yet but I feel amazing, I know it’s made an impact. I know that many medications can negatively impact your gut, so I just wondered if anyone knew about rapamycin specifically.

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#4

You told me what I was interested in hearing: avoid gums, emulsifiers, additives, etc. Sounds like a sensible approach.

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#5

Hm, good question, Christen. I hadn’t thought about the impact on gut health. Since rapamycin is an antibiotic and antifungal, it must have some effect, but it seems unlikely to have a detrimental effect in such a low dose, and there is some evidence it may be beneficial. Are you taking 2 mg/day or weekly?

This mouse study found that rapamycin had a detrimental effect on gut health in the continuous immunosuppressive doses typically given to transplant patients: Intestinal Dysbiosis Correlates With Sirolimus-induced Metabolic Disorders in Mice - PubMed

This study suggests that the beneficial effects of rapamycin on ulcerative colitis may be due to changes in gut microbiota, but it’s not clear whether it was cyclic administration or at what doses: Rapamycin extenuates experimental colitis by modulating the gut microbiota - PubMed

Finally, this study of fruit flies showed “rapamycin-mediated alterations in microbiota dynamics in aged flies are associated with improved markers of intestinal and muscle aging”: https://www.researchgate.net/publication/333352860_Rapamycin_modulates_tissue_aging_and_lifespan_independently_of_the_gut_microbiota_in_Drosophila

The researchers note that the beneficial effects on aging and lifespan don’t depend on the changes in the microbiota. It seems to be a correlation, not a cause.

If you test, it would be interesting to learn the results.

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#6

From what I’ve read, I think its still early in the microbiome research world, and we really don’t have a good idea on what an optimal microbiome is for people at different ages, for longevity, or how best to manipulate it to achieve this optimal for a given person.

It seems a little like the biological clock / epigenetic age tests you can buy. Lots of people willing to sell them to you, but not much rigorous science backing up the validity of the given test, and actions taken to “optimize” the microbiome for a given person. (If I’m wrong on this, please post the counter-evidence).

Of course, the big question is: What can we do to maintain a happy microbiome? And will it actually help us stave off age-related diseases?

There’s plenty of evidence to suggest that, on the whole, a diet with plenty of fruit, vegetables, and fiber is good for the gut. A couple of years ago, researchers found that after 12 months on a Mediterranean diet—one rich in olive oil, nuts, legumes, and fish, as well as fruit and veg—older people saw changes in their microbiomes that might benefit their health. These changes have been linked to a lowered risk of developing frailty and cognitive decline.

But at the individual level, we can’t really be sure of the impact that changes to our diets will have. Probiotics are a good example; you can chug down millions of microbes, but that doesn’t mean that they’ll survive the journey to your gut. Even if they do get there, we don’t know if they’ll be able to form niches in the existing ecosystem, or if they might cause some kind of unwelcome disruption. Some microbial ecosystems might respond really well to fermented foods like sauerkraut and kimchi, while others might not.

I personally love kimchi and sauerkraut. If they do turn out to support my microbiome in a way that protects me against age-related diseases, then that’s just the icing on the less-microbiome-friendly cake.

We’ve had some general discussions on this topic in the past:

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#7

It’s a good question. I’ve always thought that it should have an effect on the microbiome since it is exposed immediately. The effect most likely is positive since it makes us live longer. We know the effect on the oral microbiome is positive. Deep subject. Good Luck,

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#8

2 mg once weekly. I went through ageless and I believe they incrementally increase the dosage. I will definitely share what I find if I do any testing. Thanks! :slight_smile:

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#9

My N1 experience over the last year and half has been that my gut function has vastly improved over that time. I haven’t done any microbiome testing or other gut specific medical test though. I’m simply regular like clockwork now and tolerate a wider variety of foods without any problems. I had a very restricted diet when I started rapa and now I’m able to eat basically whatever I want although I still choose mainly minimally processed foods for health reasons.

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#10

That’s great! What a yummy bonus.

Based on what I’ve read or heard, it seems that rapamycin might suppress food sensitivities (a kind of immune reaction to food) and/or selectively eliminate harmful and enhance beneficial bacteria. And/or maybe other effects related to mTOR suppression?

Since mTOR is nutrient sensing (i.e., it’s triggered by eating), and rapa suppresses mTOR, downregulates cell growth, and upregulates autophagy, maybe those combine to let the gut rest, digest, and eliminate waste more effectively?

A thought popped into my head: maybe rapa affects vagus nerve function? This 2014 rat study suggests that guess may not be too far off:
Modulation of food intake by mTOR signaling in the dorsal motor nucleus of vagus in male rats: Focus on ghrelin and nesfatin-1 - PMC

Thanks for the good food for thought! :wink:

Bridget

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#11

My guess is that rapamycin improves gut health.

A little backstory: in fall 2019 I developed a severe case of gastritis, which continued to worsen over the next couple years. By fall 2021 I had lost 40 lbs and could barely eat 1,000 cal/day. In the spring of 2022 I finally found a diet that somewhat improved my symptoms, but it was very limited (white rice, boiled chicken, and a ‘clean’ brand of cookie dough bites).

In fall 2022 I began taking the ‘gut inflammation research formula’ from Peptide Sciences which contains the peptides KPV and BPC-157, along with tributyrin and palmitoylethanolamide. I took this for at least 6 months, and during this time I began being able to tolerate more foods and regain weight. I’ve continued to take tributyrin ever since, and I credit it with much of my recovery.

In fall 2023 I began taking rapamycin, and tbh, I’ve definitely improved even more since then. I can pretty much eat whatever I want now on a daily basis. Mexican, Thai, you name it. Although I try not to overdo things like garlic and onions. And I can drink alcohol too. Which tbh, I need to chill on that, because I’ve been drinking on an almost daily basis the past couple weeks.

Really the only thing I still avoid is coffee. Which sucks because coffee has a motivational magic that caffeine doesn’t for me (I still take caffeine on a daily basis). I’ve tried low acid coffee which is more tolerable, but it still gives me issues if I consume it daily. And anything that increases my stress levels like traveling does increase my symptoms.

All that said, I’m infinitely grateful to be where I’m at today. 3 years ago the future felt extremely bleak, whereas today the future feels very bright and I don’t even feel like I have any issues. Pretty much no stomach pain or spasms, if anything I just burp more than other people.

I had already improved a lot before taking rapa, so I give most of the credit to limiting my diet for months, cutting coffee, and the tributyrin. But I if I was 90% better before taking rapa, I’m 95% better now, and that extra 5% makes a huge difference tbh. I think my mental health has also improved a lot over the past couple years, and I’ve always noticed that the better my state of mind, the less my symptoms were (even when I was at my worst). Same with stress, my stress levels went way down the past couple years.

GERD and gastritis symptoms can overlap too, so I think that anyone dealing with residual gastritis symptoms should consider that they are due to GERD. When my gastritis was really bad, famotidine and Gaviscon did almost nothing for me. Now they pretty much eliminate my symptoms when my burping flares up.

Long post, but hopefully it might help anyone who’s dealing or dealt with gastritis. It really is a nasty condition, and one that gastro docs often struggle to treat.

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#12

Is there any test we can use to test the level of gut microbe in your gut?

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#13

@adriank Stool testing is a possibility but still an emerging science. I think the easiest way is to assess your “gut health”.

Poop health — Look for a Bristol Stool chart (attached)
Poop frequency— regular, frequent bowel movements
Poop retention — how much poop are you carrying around all the time (MRI…?)
Digestion issues — bloating, gas, “food allergies”, food sensitivities,
Diet composition— proper food for a diverse microbiome

If you have any issues here, then you have work to do but it will be worth the effort. It can take significant time to solve it. Be patient.

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#14

Does rapamycin kills gut bacteria?

#15

Yes it does.

“Transient (3-month) rapamycin treatment is also sufficient to alter the gut microbiome, alter cancer risk, and significantly improve lifespan when administered to middle-aged mice”

Here’s the paper. It says the effect on mouse microbiome occurred in both rapa in food and rapa injections

#16

so pro-biotic is recommended???

#17

There are several good reasons to combine rapamycin with metformin and/or acarbose. Gut health is one of them.

Gut Aging: A wane from the normal to repercussion and Gerotherapeutic strategies

3.1.1. Metformin

Metformin (biguanide with 50% bioavailability via oral route) is the most prescribed drug for the treatment of type-2 diabetes but is currently repurposed to serve as a gerotherapeutic drug [121], [122]. A study reported that a higher proportion of metformin when orally administered, accumulates in the gut (primary reservoir) and can directly regulate the gut microbiota/increased levels of Akkermansia [123]. In the intestine, it impeded stem cell aging, modulated mitochondria function, inhibited cellular senescence via restoring nicotinamide adenine dinucleotide (NAD) levels, prevented macromolecular damages, recovered tight junction protein, reduced telomere attrition, ameliorated colonic pathological inflammation via activating AMP-activated protein kinase (AMPK) while inhibiting p53 pathway and improved nutrient sensing. Of note, this drug prevented “leaky gut” by suppressing the Wnt pathway to promote the differentiation pattern of ISCs into the goblet cell, modulated the gut microbiome to increase beneficial gut metabolites, increased occludin, and reduced inflammation in old mice [127]. Although it remains effective as a gut-aging intervention, further studies are required to precisely understand its interaction with the Wnt pathway in promoting intestinal stem cell (ISC) self-renewal and differentiation.

3.1.2. Rapamycin

Rapamycin treatment as a repurposed gerotherapeutic intervention, targets the mTOR inhibition pathway and rejuvenates ISC in mice by reversing the transcription profile of aged stem cells [63]. The aging of ISCs is reported to be driven by mTORC1 via the p38 mitogen-activated protein kinase (MAPK)-p53 pathway and inhibiting it using rapamycin could be an effective strategy [95]. It is worth noting that rapamycin does not support ISC rejuvenation by Sirtuin-activating drugs such as NAD+ precursors nicotinamide riboside (Sirtuin 1 activator) which implicates mTORC1 activation in its mechanism of gut rejuvenation [94]. These findings suggest that the concomitant use of rapamycin with mTORC1 activating drugs such as NAD+ precursors nicotinamide riboside has to be avoided.

Also, rapamycin can modulate the gut microbiota, increase autophagy, improve immune function, delay immunosenescence, and exhibit potent immunosuppressive effects via modulating adaptive and innate immune responses [132], [133]. Recently, it was reported in one study that it can attenuate age-related decline by increasing lysozyme and intestinal lysosomal alpha-mannosidase V (LManV) to increase the autophagy of enterocytes in Drosophila while maintaining paneth cell structure and barrier function integrity in mice [134]. This effect was sustained even after ten days and six months of drug withdrawal in Drosophila and mice, respectively. Hence, this finding suggests that rapamycin induces a memory effect in the gut cells. Aside from the memory effect on gut cells, rapamycin also prevented inflammation by blocking the aged-related increase of NF-κB in both mice and flies.

https://www.sciencedirect.com/science/article/pii/S240584402413914X

----And here is a good article on the benefits of combining rapamycin with metformin and/or acarbose.

Optimizing Longevity Protocols: The Synergistic Potential of Rapamycin, Acarbose, and Metformin

https://gethealthspan.com/science/article/optimizing-longevity-protocols-rapamycin-acarbose-metformin

#18

This is interesting.

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#19

Yeah, I wonder if I should not use Niacin IR when taking Rapa. It increases NAD.

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#20

@Bicep Good question. I already stop everything on the weekends (which is when I take rapamycin) so I’m covered here.

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