The role the gut plays in our health is being increasingly recognized and ME/CFS researchers are not going to be left out. At least four gut studies are underway or are about to get underway and we’ve had three gut studies published in the last couple of months. This is the first to two studies from this Australian group.

Support for the Microgenderome: Associations in a Human ClinicalPopulation. Amy Wallis, Henry Butt, Michelle Ball, Donald P. Lewis & Dorothy Bruck. Scientific Reports | 6:19171 | DOI: 10.1038/srep19171

There were no healthy controls but this study examining the effects of gender on the symptoms and gut bacteria in ME/CFS was huge (n=274). The study wanted to know if the microbiome in ME/CFS was different in men and women, if some bacteria were associated with different symptoms, and if

Digestive_system_diagram_nuThey examined bacteria abundance at the genus level. (They were unable to differentiate species). Anaerobic (Bacteroides, Bifidobacterium, Clostridium, Eubacterium, and Lactobacillus) and aerobic (Escherichia, Streptococcus, Enterococcus) genera were assessed.

Why look at gender? Gender is becoming increasingly recognized as an important factor in studies. Male mice, for instance, with their simpler immune and hormonal systems have dominated research studies for decades but males can’t begin to match females more complex systems. Their prime directive – to provide sperm – pales beside the complexity needed to grow and carry a child to term.

A striking findings in laboratory animals, for instance, suggests that T-cells – not the microglia – may play a key role in producing chronic pain in women.


The symptoms found in the two groups were similar. Except for a tendency for increased pain and fatigue and neurocognitive scores, women and men tended to have similar symptoms. Nor did their gut composition differ significantly.

Men and women reacted very differently, however, to three of the main gut genera (Clostridium, Streptococcus, Lactobacillus) tested.

Clostridium, Lactobacillus, Streptococcus….

The study suggested that bacteria of the Clostridium genera could be whacking women in a number of ways. Significant small to medium correlations between the abundance of Clostridium bacteria and fatigue, neurocognitive symptoms, sleep, immune impairment and total symptoms suggested that women with ME/CFS might want to steer their gut flora in a different direction.

If Clostridium bacteria appeared to be a kind of kryptonite for women they were more like manna for men. So far as they were concerned, the more Clostridium bacteria the better; men with increased Clostridium bacterial levels had improved mood and a tendency for pain, gastrointestinal and energy production issues.

The situation was reversed with Lactobacillus bacteria. Males with more Lactobacillus bacteria had more severe symptoms overall and more neurocognitive, neurosensory, pain and mood symptoms but women appeared to be affected by Lactobacillus bacteria not at all.

Streptococcus bacteria continued the trend. Men with higher levels of Streptococcus bacteria tended to have more pain, worse sleep, more gastrointestinal symptoms, more problems with energy and more severe symptoms overall. Women, though, with higher levels of Streptococcus bacteria experienced less pain, neurosensitive problems and immunity impairments.

The Sex Divide

The differing effects of the gut flora on symptoms in men and women was intriguing given studies showing very high rates of gynecological disorders in women with ME/CFS. Those studies and others suggest that estrogen, an immune regulator among other things, could play a role in producing ME/CFS. Broderick’s immune studies suggest that testosterone, on the other hand, may play a protective role for me. The authors noted that the gut flora can effect estrogen production.

genderWith two Clostridium spp. (C. difficile, C. perfringens) being associated with intestinal dysbiosis (altered gut flora) the authors suggested women with ME/CFS may suffer from this. If it is they suggested it could be driving some of the neurological symptoms found in ME/CFS. Sugar lovers should note that these two species love the refined carbohydrates (sugars) associated with Western sugar-rich diets.

Lactobacillus and Streptococcus spp. , on the other hand, could possibly be contributing to neurological symptoms in men. These two genera contain bacterial species that produce an agent called d-lactic acid which in higher levels can be neurotoxic. L-lactic acid is easy to metabolize but humans have more difficulty metabolizing d-lactic acid.

A 2009 De Meirleir study found increased rates of D-lactic acid producing streptococcus and enterococcus spp. in people with ME/CFS.  De Meirleir reported that d-lactic acidosis is caused by the bacterial fermentation of carbohydrates in the gut which also increase gut permeabililty by lowering pH levels in the intestine. The increased gut permeability then results in increased D. lactic acid levels in the blood.

De Meirleir’s study suggested that E. coli had been largely replaced by lactic acid producing bacteria (Enterococcus and Streptococcus spp.) in ME/CFS. Why this had happened was unclear but De Meirleir suggested an enterovirus infection could be to blame.

He proposed using short courses of an appropriate antibiotic, alkalinizing agents, a low carbohydrate diet and reduced sugar intake could help.

The authors of the present paper suggested that their findings suggest that men with ME/CFS might want to be careful about using probiotics containing lactobaccillus spp. that could increase D. Lactate producing bacteria. High sugar diets alone can increase d-lactic acid levels but L. acidophilus – a commonly found bacterial species in yogurt and probiotics – mainly produces D-lactic acid.

Just as in the muscles, d-lactate or d-lactic acid causes a shift from aerobic from anaerobic metabolism. People with good digestion probably have no problem clearing the d-lactate produced by these bacteria but people with leaky gut – who may be, ironically, inclined to take these probiotics – may not. Lactic acid producing bacteria, on the other hand, can clearly be beneficial for many.

What to do? One blogger suggests the problem may not be the presence of L. acidophilus so much as the overwhelming abundance of it in some probiotic mixtures. Taking a probiotic that contains a variety of species may help or you might want to try d-lactate free probiotics.


We caution against over-interpretation of these findings considering the limitations of cross-sectional, observational research design (unable to establish causation or consequence, difficulty excluding confounding variables) and categorical analysis of genera rather than species. The authors

This study did point out some possible factors that made sense given what we know about ME/CFS. Because it was unable to identify species, however, it was less a call for a specific treatment approach than a call for more research.


Something is happening in the guts of people with ME/CFS. Exactly what is not clear yet.

D-lactate producing bacterial species, for instance, could be causing harm in ME/CFS but there’s no way to tell that they are without identifying the species involved in producing symptoms in ME/CFS. Ditto with the Clostridium spp. (C. difficile, C. perfringens) species mentioned. The authors posted hypotheses that need to be tested in more refined studies.

Multiple types of lactobacillus, streptococcus and clostridium bacteria are found in the guts of humans.  Because the researchers were unable to determine the species present it’s not which probiotics might be helpful.

Their findings suggesting that men and women with ME/CFS respond very differently to gut bacteria indicated that future gut studies should take gender into account.

The significant gut findings are starting to pile up. This study’s possible Clostridium findings in women could jive with that from Shukla’s Solve ME/CFS Initiative gut/exercise study. That study suggested that Clostridium bacteria may be contributing to leaky gut and then translocating to the blood during exercise. Maes’s 2012 study suggested translocated gut bacteria may be sparking inflammation in ME/CFS. The Lipkin/Hornig study underway has some strong preliminary findings.

Some broad outlines have been drawn. Something appears to be going on. Given the incredible bacterial diversity found in our guts, the different types of ME/CFS that surely exist, and the inability, of many studies to identify individual species, we have quite a ways to go before getting a real handle on the microflora found in ME/CFS patients guts, however.


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