Sex Differences in CFS Microbiome

A reader forwarded me a new report published today in Nature which found differences between males and female CFS suffers. The title does not indicate that it is linked to CFS/ME  “Support for the Microgenderome: Associations in a Human Clinical Population

One of the major findings is what I have speculated (without a solid study to support it): There is association between symptoms seen and bacteria in the microbiome.  Shifting the microbiome may reduce specific symptoms.


  • “In females, the Clostridium genus was positively associated with eight of the thirteen ME/CFS symptoms.”
  • “For males, an opposite association was found, with a significant negative correlation betweenClostridium RA and mood symptoms”


  • “the positive associations between the distribution of Lactobacillus and total ME/CFS symptom factors for males”
  • ” for females, no significant relationships were revealed between these variables.”


  • “Correlations for StreptococcusRA suggested opposing protective or pathogenic qualities between the sexes.”
  • “Conversely for females, there were significant negative correlations between Streptococcus RA and pain (F3:rs = −0.17, n = 154, p = 0.034), neurosensory (F5: rs = −0.16, n = 165, p = 0.040), and immunity impairments” – i.e. more Streptococus had less pain, neurosensory and immunity issues in women.


  • No significance between sexes, but:
  • “Significant, small negative correlations were shown between Bifidobacterium RA fatigue (F1: rs = −0.16, n = 166, p = 0.036), neurocognitive (F2: rs = −0.17, n = 158, p = 0.032), neurosensory (F5: rs = −0.17, n = 164, p = 0.030), energy/production and transportation impairments (F10: rs = −0.23, n = 164, p = 0.003), ICC symptoms (F12: rs = −0.19, n = 123, p = 0.044), and Total symptoms (F13: rs = −0.20, n = 117, p = 0.029) factors.” i.e. the more Bifidobacterium, the less severe symptoms.

Study’s Weaknesses

  • There were no matched controls to identify where there are dramatic shifts from a healthy population
  • The analysis was at a high level (family) and did not look at strains
  • Only four families were examined

Bottom Line

This article was largely data reporting, however in it’s discussion we find some interesting things to consider.

“Observations across Lactobacillus and Streptococcus genera suggest support for D-lactate as a contributing factor to symptom expression, particularly in males. This hypothesis explains the neurological symptoms of ME/CFS as a consequence of neurotoxic effects of bacterial metabolites (i.e., D-lactic acid produced by most species of Lactobacillus and Streptococcus) on the brain and nervous system25. Increased D-lactic acid levels have been found in the serum of CFS patients with intestinal bacterial overgrowth7, associated with cognitive and neurological impairments26, and reduced in response to treatment in a sample of CFS patients27. The mechanisms of a sex-specific response to D-lactic acid have not been considered.”

” Notably, the findings for Lactobacillus spp. in males caution against premature probiotic supplementation with D-lactate producing bacteria. However, results support the health-promoting effects of Bifidobacteria as observed across diverse disease states including IBS28,29, cancer30, anxiety and depression31,32.”

My Take Away

The results appears to be in close agreement with my general model and supports my view that:

  • Most Lactobacillus probiotics should be avoided
  • Most Bifidobacteria probiotics should be taken

The role of Clostridium is fuzzy, but it suggests that Miyarisan (clostridium butyricum) may help to moderate the symptoms in at least one sex. It may improve in both (displaced the bad ones).

Streptococus role is interesting because it was been reported as low in CFS. This family is common in oral probiotics and suggests that supplementation may improve symptoms.