Everything is a balancing act. As Doxy is an antibiotic it has the potential for harming the gut microbiome. It may be possible to counteract that negative effect with diet and pre and pro biotics, exercise, etc.
Interesting find, thanks for bringing this information to the table!
Some publications suggest doxy- or minocycline taken at low doses do not exert significant antimicrobial activity, which may prevent the disruption of normal flora and reduce the risk of developing antibiotic resistance. Low dose doxy- or minocycline is mostly used for its potential anti-inflammatory effects.
But on the other hand: a recent study concluded that a year after one time antibiotic use, there were still observable changes in the intestinal microbiome. Whereas earlier studies suggested after one-time use the microbiome commonly recovers within months. Imho this confirms again there are likely so many things about the microbiome that we don’t known yet.
Personally I wouldn’t dare to use doxy- or monocycline on a regular basis; let alone taking a low dose daily.
I’m always a bit surprised when it is brought up that some pre- and probiotics can resolve dysbiosis caused by antibiotics. Most commonly the ability of probiotics to establish permanent residence is limited. (That’s besides the fact that we’re just randomly using some strains with no idea whether they may start to dominate/outcompete other strains while using the probiotic, etc. And that’s besides the fact that many probiotics may not even be active anymore - albeit some research suggests ‘dead’ probiotics may still have some effects on the microbiome, potentially apparently because of ‘bioactive compounds that are released when bacterial cells dissolve in the digestive system’).
I concur (always wanted to use that one) that taking low dose antibiotics is not for me either due to the high potential for unintended consequences. At least with our fav experimental drug Rapa it appears to have some benefit to the gut microbiome.
Agreed on the gut “helpers” thing as it remains a significant mystery and there are significant “works”, “doesn’t work” studies on how to restore/maintain it.
I just did a quick headline review on the Doxy effects and one thing it appears to do is change gene expression of various gut microbes that could lead to microbial resistance.
This particular study is one of the more extreme use cases as it involves HIV positive and exposed folks who are on higher doses.
Significant tetracycline resistance genes (ARGs) were detected among the analyzed samples, revealing that tetracycline ARGs were the most prevalent in the resistome, accounting for a substantial portion of the mass.
I’ve read this before, one of the plastic surgery publications, I think. No salvation until genetic therapy is perfected. Likely that would be in 1,000 years.
I take it daily at the low dose range because of my unique risk - reward. I want to reduce the risk from impact on microbes but I want the benefits - in my case impact on inflammation (I’ve got MS so reductions in inflammation is good for me)
Inflammation is often site and condition specific, are you targeting a specific site or is this for systemic inflammation ? I see you have noted a specific condition.
There are quite a few things that can reduce inflammation, some systemic, some site specific. I’m going to be trying (GLY14)-HUMANIN soon and may add Dulaglutide to one of my stacks as GLP1-R’s are being studied for systemic and brain inflammation.
The gene therapy thing may be an answer as long as it can be controlled. We’re talking about stimulating the production of something with a 70 year half life which if not controlled could turn us into a ball of rubber LoL! and that is why we stop making it around puberty.
I’ve mentioned this before, evolution does not care how long we live, only that we procreate and continue the species. After that, evolution is done with us.
Elastin is incredible stuff.
Aren’t there stool-based tests for microbiotic health that you can do? Would be interesting to see how things are after being on the low-dose doxy protocol. I prescribe low dose doxy on occasion for patients with rosacea who are recalcitrant to topical therapies. I prefer the 20mg tablets twice daily with food (to keep the total dose and the peaks low). There’s a 40mg sustained release version, but I’ve given up on it for now due to prior authorization headaches even though it’s gone generic. There’s also a new 40mg branded sustained release minocycline that just got approved.
Thorne has a test with analysis of bacteria. Pretty informative, even predicting amount of antibiotics you’ve taken in lifetime.
Wow, this is big news, and good news at the same time. Thanks for sharing.
Will you use CRP as your measure for inflammation? Keep us posted. I’m watching/waiting to try low dose GLP1 for systemic inflammation - osteoarthritis in my hands is inhibiting my life at age 64.
I have old skin and it has seen a lot of sun. I watch this topic with interest and have tried oneskin and a few others just to see what they do. Not that I care very much, but I like to try things.
I recently bought a bottle of Tremella mushroom capsules. Tremella was of interest when I was starting to grow mushrooms, but it’s a little harder than most because it’s a fungus that grows on another fungus and I’m not that good at just one fungus so never gave it a try. It has been used for thousands of years as a skin moisturizer and is supposed to be able to hold 500 times it weight in water.
I think the capsules work better than anything I’ve tried. My skin is very smooth. I bought this from @Joseph_Lavelle and forgot the web site but it’s not that expensive.
Just stuff I found from Google
I’m very limited in the testing I can get done here for a reasonable price. So I’m more interested in the visible/physical effects and some basic measurements I can do at home.
For osteo, clearing out senescent cells appears to be one way to reduce inflammation that may be closely tied to that condition.
What is interesting about senescent cells is how many conditions they play a part in. I tell people to pick their favorite disease/condition and do a google search like this > heart disease senescent cells <> osteoarthritis senescent cells < just tack on > senescent cells < to any condition and you may be surprised.
I’ve been “killing” my senescent cells for about 4 years but the method I’ve been using is tissue specific and does not appear to fully address the tissues involved in OA. One of the reasons I’m about to try an interesting peptide called FOXO4-DRI in January. I have arthritis in my left hand, and my little finger is where it’s most prevalent, so I’m interested to see if FOXO4-DRI helps.
Asking Google AI > osteoarthritis senescent cells < I get this answer.
" AI Overview
Yes, senescent cells are a key factor in the development of osteoarthritis (OA). Senescent cells are cells that have undergone a process of cellular senescence, which can occur in many tissues, including cartilage, synovium, and subchondral bone. In OA, senescent cells contribute to the disease in a number of ways, including:
Creating an inflammatory environment: Senescent cells secrete cytokines that impact the immune system and can contribute to inflammation.
Altering the synovial microenvironment: Senescent cells can alter the synovial microenvironment, which can lead to OA-like arthropathy.
Degrading cartilage: Senescent cells can contribute to cartilage degradation.
Some markers of cellular senescence include: Beta-galactosidase expression, Telomere length, Mitotic activity, and Senescence-associated secretory phenotype (SASP).
This is interesting! My skin is as dry as the Sahara. For the first time, I just ordered hyaluronic acid in pill form to see if I could moisturize from the inside out.
Is that the effect it had on your skin? Or did you mean something else when you said it helped smooth your skin? (Aside from dehydration, my skin is pretty good).
I imagine you got this from his fullscript store!
@Joseph_Lavelle any comments on tremella ?
Fullscript is correct. I am a little busy and just didn’t have time to look it up.
All the rough areas become smooth. It’s crazy how fast it works. I’m interested in finding out how it works on other people. Most of my problems seem to come from my skin being so thin and that seems to cause wrinkles too. There’s no plump. This seems to help noticeably.
Black Friday has arrivedfor the NIRA laser
Thanks, I thought I’d been cleaning up senescent cells with Rapamycin. I’ve been taking it for over 2 years and generally feel fantastic, except for my worsening hands. Will you do this FOXO experiment with or without Rapa?
Re tests, yes I’m Canadian too but planning to get some tests, including Rapamycin levels, done in San Diego when I visit there soon. If anyone has a lab to recommend, let me know. Labcorp had a heckuva time dealing with my lack of US address even though I used my son’s.
While Rap does have senolytic properties and inhibits SASP, I do not think it is the best nor the most effective senolytic.
I will continue to do our Rapa cycle as we introduce FOXO4-DRI. My approach is to maintain my baseline. Our baseline currently includes a lot of things so I like to leave that “as is” when I add or try something new unless there is a conflicting issue.
I have not read enough to fully understand how effective Rap is nor what the effective dose is for it to act effectively on senescent cells. When it comes to senolytics, dose often critical. For example Quercetin is not a senolytic at low does. What is a low dose of Q? under 2000 to 3000mg it’s not very good at all forthat purpose but it’s beneficial at low 500mg doses for other things.
Rapa is more of an inhibitor of senescence. But again, at what dose? and in humans or mice?
AI Overview
Yes, rapamycin has senolytic-like properties:
Rapamycin can suppress senescence and the senescence-associated secretory phenotype (SASP).
Rapamycin can inhibit cellular senescence in multiple cell types, including fibroblasts.
Rapamycin can delay entry into senescence in cells treated with chemical stress, ionizing radiation, and other factors.
Rapamycin can reduce senescent cell subpopulations.
Here is an article by Mikhail V Blagosklonny whom most of us taking Rap are aware of.
It is working amazing for me. 30 days in 
Crap… If @Walter_Brown and @Bicep say something is good… That means l will be getting another supplement.