The HPA axis has long been a subject of interest to me as a ME/CFS sufferer. In particular, when I first read about the
Cortene hypothesis, it made a lot of sense to me. At this point,
the HPA axis seems like a core element of ME/CFS pathogenesis, though obviously not the only element, and of course I am only offering my opinion as a relative layperson in the medical field. Nonetheless the following may be of interest to some of you.
About two months ago, I stumbled upon this paper -
“Bifidobacterium longum and Lactobacillus helveticus Synergistically Suppress Stress-related Visceral Hypersensitivity Through Hypothalamic-Pituitary-Adrenal Axis Modulation"
It studies a novel combination of two commercially available probiotic strains in mice. The intended application in the paper is to treat IBS, and when sold to people, these strains are commonly marketed as a ‘mood probiotic’, but in each case the purported mechanism through which the probiotics exert a benefit is the HPA axis.
I found this particular finding from the paper to be the most intriguing:
"the expression of the glucocorticoid receptor mRNA was consistently up-regulated in several brain areas after pretreatment with a combined probiotic".
If you need a refresher on the HPA axis, the hormones which constitute it function as part of a feedback loop. The hypothalamus produces CRF (also called CRH) which activates CRF receptors in the anterior pituitary. This causes the release of ACTH, which activates ACTH receptors in the adrenal cortex. Finally, this causes the release of cortisol, which activates glucocorticoid receptors, among others. Cortisol goes on to
suppress the release of CRF and ACTH, keeping the levels of these hormones and their receptors in balance.
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There are two subtypes of CRF receptors - CRFR1, which is expressed against minor ‘homeostatic threats’, and CRFR2, which is expressed against major ‘homeostatic threats’. After dealing with a major homeostatic threat, such as a severe illness, the CRFR2 is supposed to downregulate, but according to the Cortene hypothesis, in ME/CFS the CRFR2 is ‘stuck’ upregulated (normally, the 5-HT1A serotonin receptor governs CRFR2 downregulation, but it seems like it gets desensitized from chronic stress). And since CRFR2 is upregulated, and does not respond to the inhibitory effect of cortisol, the body overproduces cortisol, leading to downregulation of glucocorticoid receptors, and eventually a depletion of cortisol (indeed, many people with ME/CFS suffer from mild to moderate hypocortisolism or other cortisol-related abnormalities).
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Back to the probiotic -
if it does indeed increase the expression of glucocorticoid receptors, sensitizing the body to cortisol, presumably it would increase the negative feedback that cortisol has on CRF and ACTH release. And even if it did not fix the feedback loop entirely, there would probably be some benefit to restoring glucocorticoid receptors to their normal sensitivity.
After finding this paper, I decided to buy the probiotics and give them a shot.
They are produced by Innovix Labs, and you can find more information about them on their website. As far as I can tell, probiotics are a pretty low-risk intervention - lactobacillus and bifidobacterium strains
sensu lato are very well studied, and this particular combination of strains probably has the same risks as most other garden-variety probiotics (obviously people with known sensitivity to probiotics, due to conditions like SIBO or something, should exercise caution). In the past, other probiotics have given me some nasty side effects, primarily gastrointestinal, but this combination of strains did not seem to cause any, even initially.
It’s been around a month and a half since I started taking them, and
I have seen a distinct improvement in my ME/CFS symptoms, more so than virtually every other intervention I have tried. On
Dr. David Bell’s ME/CFS disability scale, I was at a 10 before I started taking the probiotics, and now I am sitting around a 20. This does not seem like a huge improvement, but there are a ton of different quality-of-life changes I’ve been able to make. I can now do minor chores, such as doing my laundry or cooking a small, simple meal without getting any PEM. I can now actually read for 30 minutes or so without crashing, and my tolerance of sight/sound has also gotten somewhat better. My mood has also been especially good, though it’s unclear whether that’s a direct consequence of the probiotics, or just happiness from my health improvements.
When I do overexert myself, the PEM is also not as severe and I seem to bounce back after only a couple of days. For instance, I had to make an emergency dental appointment after my molar cracked in half. Normally these kinds of doctors visits (especially something as stressful as a tooth extraction) would make me totally bedbound for a week or more, and I wouldn't truly get back to baseline for what felt like a month, but after this one I was pretty much back to baseline in 48 hours.
All that said, there are definitely other variables to consider. To begin with, I had severe IBS for years prior to getting ME/CFS. I’ve always thought that my CFS was inextricably linked to my gut, and so maybe probiotics are affecting my disease process in a way that wouldn’t necessarily have the same benefits for others. However, IBS-spectrum illness is common in ME/CFS, and it’s possible that gut flora imbalance could be a contributing factor even in the absence of serious GI symptoms.
I also have been receiving IVIG therapy for six months to treat autoimmune small fiber neuropathy. It usually takes months to years to see the full extent of improvement from IVIG, so it’s possible some of my health improvements may be partly due to ongoing IVIG therapy. However, my IVIG improvements to date have been mostly on my nerve pain and not my fatigue/PEM, and it would be a bit unusual for IVIG to lead to such rapid improvements, almost ‘all at once’, after many months of slow progress.
In any case, I am curious if other people have tried this particular blend of probiotics. I think they are definitely worth a shot, especially if you feel like gut flora issues have played a role in your ME/CFS. They are fairly inexpensive, and seem to be fairly low-risk as far as supplement-type interventions go.
