A short guide to improving your microbiome

Akkermansia muciniphila go brrrrr

Dec 16, 2022

This is directly connected to the substack below (kinda obviously).

Covid infection causes long-lasting microbiome instability

This is the “other half” of the following substack. They are independent of each other, but reading both will give you a broader understanding of the changes going on, if you didn’t read it, I would advise you to. Before we delve into this paper, and further down this nest, I would like to point out that for the longest part I wrote that Omicron was shif…

3 years ago · 49 likes · 36 comments · John Paul

By sheer chance, I decided to check out any other ways to modulate the precise microbe Omicron impacts long-term, since a liver drug helps with it, and using the microbe as a supplement (probiotic) influenced insulin sensitivity and many other metabolic and inflammatory-related markers.

The following has a two-fold purpose, to help people worried or affected by Omicron, especially the ones hit in the gut, and to once again demonstrate that usually, the stack (group of supplements) I recommend is pretty much one of the best starting places to solve a lot of SARS-CoV-2 or inflammatory issues. This will be short and direct, I have covered enough scientific literature here, so if you want a more complex analysis of it, I highly recommend you use the search function here in Substack (it is a pretty good one, I use it all the time myself).

To be completely clear, all these supplements play multiple roles, the following are related to just this issue alone.

First, we started with one of my “main” supplements and one I recommend to any person with any type of gut issue (or depression/anxiety, or sleep issue). Melatonin.

Metformin Is Associated With Higher Relative Abundance of Mucin-Degrading Akkermansia muciniphila and Several Short-Chain Fatty Acid–Producing Microbiota in the Gut

RESULTS

We found an association between diabetes and gut microbiota that was modified by metformin use. Compared with participants without diabetes, participants with diabetes taking metformin had higher relative abundance of Akkermansia muciniphila, a microbiota known for mucin degradation, and several gut microbiota known for production of SCFAs, including Butyrivibrio, Bifidobacterium bifidum, Megasphaera, and an operational taxonomic unit of Prevotella. In contrast, compared with participants without diabetes, participants with diabetes not taking metformin had higher relative abundance of Clostridiaceae 02d06 and a distinct operational taxonomic unit of Prevotella and a lower abundance of Enterococcus casseliflavus.

CONCLUSIONS

Our results support the hypothesis that metformin shifts gut microbiota composition through the enrichment of mucin-degrading A. muciniphila as well as several SCFA-producing microbiota. Future studies are needed to determine if these shifts mediate metformin’s glycemic and anti-inflammatory properties.

Metformin Exerts Anti-inflammatory and Mucus Barrier Protective Effects by Enriching Akkermansia muciniphila in Mice With Ulcerative Colitis

The present study aimed to determine if metformin exerts anti-inflammatory and mucus-protective effects via the gut microbiota. Metformin has extensive benefits including anti-inflammatory effects. Previous studies showed that metformin changed the gut microbiota composition and increases the number of goblet cells. Intestinal dysbiosis and goblet cell depletion are important features of ulcerative colitis (UC). The underlying mechanism and whether metformin can improve the mucus barrier in UC remain unclear. Metformin (400 mg/kg/day) was administered to mice with dextran sulfate sodium (DSS)-induced UC for 2 wk to investigate the effects of metformin on the intestinal mucus barrier.

The gut microbiota was depleted, using antibiotics, to explore its role in the mucus-protecting effects of metformin. Akkermansia muciniphila (A. muciniphila), which was enriched in metformin-treated mice, was administered to mice to investigate the effects of the bacteria on UC and the mucus barrier. Metformin attenuated DSS-induced UC in mice, as evidenced by the alleviation of diarrhea, hematochezia, and the decrease in body weight.

The expression of mucin2, a prominent mucus barrier protein, was increased in the metformin-treated group compared to the DSS-treated group. Furthermore, fecal 16S rRNA analysis showed that metformin treatment changed the gut microbiota composition by increasing the relative abundance of Lactobacillus and Akkermansia species while decreasing Erysipelatoclostridium at the genus level. Antibiotic treatment partly abolished the anti-inflammatory and mucus-protecting effects of metformin. Administration of A. muciniphila alleviated the colonic inflammation and mucus barrier disruption. Metformin alleviated DSS-induced UC in mice and protected against cell damage via affecting the gut microbiota, thereby providing a new mechanism for the therapeutic effect of metformin in patients with UC. This study also provides evidence that A. muciniphila as a probiotic has potential benefits for UC.

I am aware that Metformin is prescription-only in some countries, and while not illegal to import most prescription drugs, some people are not comfortable either doing so or just taking an actual drug. As a simplistic rule of thumb, Berberine is as almost 1 to 1 analog to Metformin, with both the supplement and the drug sharing dozens of the same positive health effects.

Berberine treatment increases Akkermansia in the gut and improves high-fat diet-induced atherosclerosis in Apoe-/- mice

Results: Berberine treatment significantly reduced atherosclerosis in HFD-fed mice. Akkermansia spp. abundance was markedly increased in HFD-fed mice treated with berberine. Moreover, berberine decreased HFD-induced metabolic endotoxemia and lowered arterial and intestinal expression of proinflammatory cytokines and chemokines. Berberine treatment increased intestinal expression of tight junction proteins and the thickness of the colonic mucus layer, which are related to restoration of gut barrier integrity in HFD-fed mice.

Conclusions: Modulation of gut microbiota, specifically an increase in the abundance of Akkermansia, may contribute to the antiatherosclerotic and metabolic protective effects of berberine, which is poorly absorbed orally. Our findings therefore support the therapeutic value of gut microbiota manipulation in treating atherosclerosis.

At this point in researching this particular angle, I was wondering, even though I was over-simplifying it if Akkermansia itself is affected by diet since it directly affects your metabolism in many ways. Color me surprised.

The Role of the Gut Microbiota on the Beneficial Effects of Ketogenic Diets

The authors also found that a ketogenic diet reduced overall alpha diversity, while increasing the relative abundance of Akkermansia muciniphila. This is of note, since a reduced alpha diversity is generally associated with worsened metabolic outcomes [26], whereas high abundance of A. muciniphila, a known short-chain fatty acid (SCFA) producer, is associated with improved metabolic health [27,28]. SCFAs are microbially produced metabolites that are implicated in metabolic health. The most commonly studied SCFA are propionate, acetate and butyrate, and these are mainly produced from gut microbial fermentation of fibres [29]. Increased levels of SCFA have been implicated in lower levels of obesity and higher levels of insulin sensitivity [30,31], and it is currently thought that the beneficial effects of A. muciniphila following a ketogenic diet are exerted by changes in plasma levels of SCFAs [17]. Importantly, the results of the aforementioned study were not confounded by weight changes, as the ketogenic diet treated mice had similar weight distributions compared to the control diet treated mice.

The finding that a ketogenic diet can increase A. muciniphila is in contrast with a previous study, which shows that following a VLCKD resulted in lower alpha diversity and A. muciniphila levels [32]. It is likely that this effect is mediated by the fact that a VLCKD also has extremely reduced complex carbohydrates (i.e., fibres), which serve as a fuel source for micro-organisms, such as A. muciniphila [33]. It is thus important for the interpretation of the results to define the exact amounts of (complex) carbohydrates when conducting an intervention trial using a ketogenic diet.

Your microbiome in your gut might be responsible for the positive effects of a low-carbohydrate diet/ketogenic diet on epilepsy and neurodegenerative diseases.

And of course, the best and cheapest way, and one I advise everyone to apply is the following. And the best part is it is free.

Islamic fasting leads to an increased abundance of Akkermansia muciniphila and Bacteroides fragilis group: A preliminary study on intermittent fasting

A total of nine subjects were included in this study during Ramadan, consisting of 17 h of fasting/day during a 29-day period. Stool samples were collected at baseline and the day of the end of Ramadan. 16S rRNA qPCR assay has been performed for quantification of Akkermansia muciniphila, Faecalibacterium prausnitzii, Bifidobacterium spp., Lactobacillus spp., Bacteroides fragilis group, and Enterobacteriaceae. Blood samples were also collected to test for metabolic and nutritional parameters.

Results

A significantly increased abundance of A. muciniphila and B. fragilis group was observed in all subjects after Islamic fasting when compared with the baseline levels (p=0.004 and 0.008, respectively). Serum fasting glucose and total cholesterol levels were also significantly reduced in all of the subjects (p<0.01 and p=0.009, respectively).

Conclusion

Islamic fasting, which represents intermittent fasting, leads to an increase in A. muciniphila and B. fragilis group, which were considered as healthy gut microbiota members. Although this is a pilot study, which should be tested with larger sample size, there are a very limited number of studies in the literature on fasting and microbiota in human subjects. Thus, our present findings may contribute to the understanding of fasting-gut microbiota interaction.

Every single supplement (and the only drug here) not only have been overlooked, but vilified for most of the last 3 years, and while there is now evidence to prove their efficacy, there is also a great effort to ban most of these from access of most of the population, or making them prescription-only (and most doctors are completely oblivious to the effects of supplementation on health, completely captured by pharma). One has to wonder about the state of things.

Overall, if you followed my “stack” you were probably already alleviating the microbiome effects of the virus, of course, this isn’t the one all, be-all, but now anyone reading this has more options than opting for a liver drug or buying probiotics, which sometimes are either expensive or impossible to access in certain areas of the world.

As usual, I appreciate everyone who chooses to support my Substack by paid subscription or whenever one of you uses Kofi, and everyone who shares this substack too.

I wish you all a good weekend.