Gender vs. Microbiota Transfer Therapy

We often get the question of whether one can adopt male characteristics if they are a female recipient of a male FMT donation (and vice versa). The idea that this can occur has been spread by those who don’t understand how sex hormones are created and broken down. Including the role that the gut and microbiome play in this. While you can’t adopt male characteristics as a female using a male FMT donation, studies demonstrate that the hormones present in a faecal transplant can impact the state of the microbiome. The hormones appear to have a short term effect at most, but what is important to note is that the sex of your donor does not matter so much as their microbiome’s ability to regulate hormone metabolism in your favour.

What differences are there between the male and female microbiome?

The bacteria-to-human cell ratio is different between genders, that is, higher in women than in men. The bacteria-to-human cell ratio is 1.3 in men and 2.2 in women.

We know that hormones influence gut homeostasis.

Male and female patients with high testosterone or estradiol levels showed a more diverse gut microbiome.

Epidemiological studies suggest a female predominance of IBS. Meaning that IBS is more common in women. Also implying the effect of female sex hormones on its etiology.

Estradiol prolongs the survival of B cells (and other immune cells). Sustained exposure results in a pro-inflammatory environment with altered intestinal gut permeability, in turn causing the migration of gut microbiota into the connective tissue of your mucosal lining, which again promotes inflammatory processes.

Hormone Metabolism

Once our hormones have delivered their message to our hormone receptors they are normally broken down by the liver or within the tissue in which the receptor was.

But, the microbiome also breaks down hormones.

The estrobolome is the collection of microbes which produce enzymes which up or down regulate estrogen metabolism. For example, beta-glucuronidase, produced by E-coli can reabsorb estrogen into systemic circulation.

Particular microbes can convert testosterone into DHT; a more potent metabolite of testosterone. The microbiome can also further break down DHT and androgens.

What do we want from FMT?

In thinking about what we want from FMT, as women we want a microbiome that effectively responds to our hormonal rhythms. Metabolizing estrogen so that there isn’t too much, and promoting progesterone production. We don’t want too much testosterone or DHT either. If our body produces too much estrogen we want a microbiome that doesn’t promote it’s reabsorption. If we have low progesterone levels we want to grow or adopt a microbiome that increases progesterone. As you’ll see if you explore the research cited below testosterone via FMT may actually have a therapeutic benefit.

As men we don’t want all of our testosterone pulled into estrogen. We want good amounts of testosterone, but not too much either.

Let’s consider some research.

When female Type 1 Diabetic mice received gut bacteria from males, it actually slowed the autoimmune disease progression down.

Your first thought might be that the testosterone in males is creating a different environment in the gut, causing it to host a different diversity of species. It's a reasonable guess, but not fully correct. The researchers found that the transplant of gut bacteria caused a surge in testosterone production by females that lasted up to 14 weeks and then went away. This had no effect on the female's fertility, but it did alter immune function. If the authors injected these mice with a testosterone inhibitor, the diabetes protection went away.

Is it the bacteria then? Do they influence immune function by interacting directly with immune cells? This also isn’t the whole picture. And we truly don’t know the answer as of yet why the male samples slowed disease progression or put the female diabetic mice into remission when female donations did not.

Sex differences in the immunological effects of microbiota transfer

A recent study performed FMT from specific pathogen free (SPF) mice to germ-free (GF) mice of the same or opposite sex, and examined effects on weight loss, organ-specific T and B cell immunity and gene expression in the gut. Female mice receiving female transplants maintained their normal body mass, whereas females receiving male microbiota or male recipients of either male or female microbiota lost weight.

The microbiota first adapted to the sex of the recipient, but by 4 weeks, some donor-specific sex differences become apparent. Mice receiving female microbiota had higher levels of double-negative T cell precursors compared to mice receiving male microbiota, suggesting a sex-dependent effect of the GI tract microbiota on T cell development. However, there were no sex differences in T helper (Th) types Th1, Th2 or Th17 cell subsets in PP, mesenteric lymph nodes (MLNs) or spleens.

In another study, transfer of male microbiota to GF males led to greater RORγt+ Foxp3+ T cells (i.e. those that inhibit Th2 mediated pathology) Th2 being the driver of allergies. This may explain the greater propensity of females to food allergies.

What do I want you to think about?

If you are a person experiencing hormone imbalance you’ll want to cultivate a microbiome that supports the breakdown of the hormones in excess or the production of the hormones that are deficient.

If you have a tendency for high estrogen you do not want to adopt a microbiome nor cultivate a microbiome that makes higher levels of beta-glucuronidase. This means avoiding FMT from persons with elevated levels of Salmonella or E-coli, which make beta-glucuronidase. But, you also want to follow a diet that does not encourage growth of those microbes. Diets high in animal protein encourage the growth of the aforementioned genus.

If you have experienced dis-ease involving high testosterone levels you do not want to adopt a microbiome that produces more DHT, which is even more potent than testosterone. Instead you want to adopt or cultivate a microbiome that reduces androgens efficiently for excretion. Might an FMT donation containing higher testosterone or DHT levels aggravate your symptoms? Yes it might.

Certain microbial signatures can be predictive of serum hormone levels, but this is not necessarily sex specific.

Plenty more research is needed in this area. But, as of yet I don’t believe we can say that females should only receive FMT from females or males only receive FMT from males. It’s not that simple.

References

Yoon K, Kim N. Roles of Sex Hormones and Gender in the Gut Microbiota. J Neurogastroenterol Motil. 2021 Jul 30;27(3):314-325. doi: 10.5056/jnm20208. PMID: 33762473; PMCID: PMC8266488.

New England Journal of medicine, 2013. DOI: 10.1056/NEJMoa1205037 and Science, 2013. DOI: 10.1126/science.1233521 (About DOIs).

Wang JJ, Wang J, Pang XY, Zhao LP, Tian L, Wang XP. Sex differences in colonization of gut microbiota from a man with short-term vegetarian and inulin-supplemented diet in germ-free mice. Sci Rep. 2016 Oct 31;6:36137. doi: 10.1038/srep36137. PMID: 27796317; PMCID: PMC5086848.

Mayneris-Perxachs et al. Microbiome (2020) 8:136 https://doi.org/10.1186/s40168-020-00913-x