Actual Improvement in PEM with Probiotics - My N=1 Experience

[katabasis]

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.

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).

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.

 

[Rufous McKinney]

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.

I decided to Go For It..ordered a bottle, I'll report back.

I dont' normally take probiotics for various reasons....I've had odd reactions before and my chinese herbalist is not a believer in throwing down who knows what. That combination led me to sort of not take them very often.

However, I'm intrigued and willing to give these a try.

 

[hapl808]

I've tried their multi-strain blend and found it moderately helpful, but nothing major. I wonder if this more targeted product would be more helpful.

 

[YippeeKi YOW !!]

Thank you for posting this info @katabasis .... Like you, Ive suspected some sort of interpolation of the HPA axis as part of the jigsaw puzzle of this creepy little bore-worm of an illness for a while now, along with a few other things, largely because of the cortisol issues that about half of this community have.

Do you know off-hand what strain of B. longum and L. helveticus is in the Innovix product. It can make a difference in terms of effective performance.

As far as I can tell, probiotics are a pretty low-risk intervention - lactobacillus and bifidobacterium strains sensu lato are very well studied,

They're both, if Im remembering correctly, usually part of the commensal gut microbiome, which would make them less risky than other, more exotic bacterias, but probiotics are not quite the benevolent, low-risk, give-it-a-whirl-what-can-you-lose treatment modality that they've been cracked up to be.

And that they've been studied sensu lato, as opposed to sensu stricto leaves wiggle room for a lot of slip twixt the cup and the lip, particularly when dealing with ME populations, whose reactions to everything are unpredictable and often wildly paradoxical and diverse, even when dealing with something as relatively straightforward and simple as magnesium supplements or Vit D ....

I felt the need to insert that caveat, because I know how desperate we all are for a cure, or an amelioration, or just anything that will help, whether it's a little or a lot, and didn't want to leave the impression that this would be a totally safe, risk-free intervention, tho it's probably in the lower-risk category, as opposed to something like Abilify .... But I've also read other member's experiences with probiotics in these threads, some of them fairly unpleasant, tho hardly deadly.

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.

Like you, I had a lengthy series of rounds with IBS-M, which is where my very early research was channeled.

That was before the ME flattened me completely and all research stopped for several years, but I also know that quite a few other members here have had the same IBS experience and share the same sense that we have that somehow, the gut and it's little armies of happily toiling bacteria, have a much larger hand in ME than previously believed or researched (@ljimbo423, I'm looking at y'all). So your supposition regarding that belief and/or condition making experimentation with decent probiotics a useful investigative tool, as well as a useful treatment, are apt, and quite possibly even for those members who haven't had the fun and frolic of IBS either preceding or accompanying their ME.

Again, than you for posting this info, and hopefully, you'll get more input and further feedback from other members here who try the Innovix product ....

 

[YippeeKi YOW !!]

I wonder if this more targeted product would be more helpful.

It might be. I think that, at least starting out, using two or no more than three strains of carefully chosen probio strains is a better way to go than bombarding your native microbiome with a whole host of potentially unwelcome, and sometimes unfriendly, intruders can be counterproductive, or even unpleasant, like the War if the Roses in your gut ....

 

[katabasis]

Do you know off-hand what strain of B. longum and L. helveticus is in the Innovix product. It can make a difference in terms of effective performance.

The strains in question are B. longum Rosell 0175 and L. helveticus Rosell 0052. B. longum and L. helveticus are pretty common components of commercial probiotics, so it does seem more likely that the strain is more important in this case than merely species-level specificity.

They're both, if Im remembering correctly, usually part of the commensal gut microbiome, which would make them less risky than other, more exotic bacterias, but probiotics are not quite the benevolent, low-risk, give-it-a-whirl-what-can-you-lose treatment modality that they've been cracked up to be.

I agree that probiotics are not totally risk-free, though as you state, their potential negative effects can be 'fairly unpleasant though hardly deadly'. Like I mentioned, people who have had trouble with probiotics in the past or have a condition like SIBO should think twice about this. Same goes for the immunocompromised, people with short bowel syndrome, or with pancreatitis. And of course there is the fact that ME/CFS makes things less predictable, though this applies to all medical interventions and is something I hope people keep in mind for all medical advice etc. offered on this forum.

It might be. I think that, at least starting out, using two or no more than three strains of carefully chosen probio strains is a better way to go than bombarding your native microbiome with a whole host of potentially unwelcome, and sometimes unfriendly, intruders can be counterproductive, or even unpleasant, like the War if the Roses in your gut ....

This is a good point. Up until now, a lot of the probiotics I've taken have been broad-spectrum attempts to fix my gut flora as a whole. I've done extensive microbiome testing so my strategy was always to try to add whatever seemed missing, and to use diet/supplements to tamp down whatever was overgrown. But I think now that it might be more effective to use a limited number of strains that are shown to have some particular benefit, and then see what response you get, perhaps even a cascade of responses that end up leading to positive changes to the gut as a whole.

 

[Rufous McKinney]

The strains in question are B. longum Rosell 0175 and L. helveticus Rosell 0052. B. longum and L. helveticus are pretty common components of commercial probiotics, so it does seem more likely that the strain is more important in this case than merely species-level specificity.

I'm wondering if you can ....somehow...slip the probiotic into the colon...and skip the small bowel...

I suspect I"m undiagnosed SIBO. Whatever is the cause of that, something is letting bacteria into the small intestine that should not be there.

 

[Rufous McKinney]

Can a probiotic be used as a suppository?

Has anyone tried that?

 

[katabasis]

Can a probiotic be used as a suppository?

Has anyone tried that?

I've never made a suppository from a commercially available probiotic, but it is a viable way to get bacteria into your gut. It's functionally similar to receiving an FMT (I actually have had an FMT, for treating C. Diff).

I wouldn't just put the pill in your rectum; you'd probably want to make a suspension of the capsule's content in sterile saline and then use a syringe (minus the needle obviously) to administer it.

However, there is certainly a greater degree of risk for the average person to administer probiotics rectally as opposed to the typical oral route. When taking probiotics orally, the bacteria have to make it through the gauntlet of digestion before ending up where they are supposed to be. Stomach acid can kill many bacteria, and while this may reduce the efficacy of oral probiotics, it may also be protective against excessive amounts of bacteria, as well as specifically against pathogenic bacteria. If you administer bacteria rectally, there is no similar line of defense. You are assuming that the quantity and composition of bacteria being administered (including any incidental contamination) is safe exactly as-is when translocated to your colon.

I'm not especially familiar with these home-brew probiotic enemas, but cursory reading shows that a few people have had negative effects from them. It's possible that whatever probiotic they took would have had similarly negative effects orally. It's also possible that these negative effects were tantamount to IBS-spectrum indigestion, likely to resolve quickly over time. However this is very much uncharted territory, so you should tread without with caution if you decide to pursue it.

 

[YippeeKi YOW !!]

so you should tread without caution if you decide to pursue it.

... treat WITH caution? Yes?

I agree. Dicey and somewhat risky .... who knows what's hitchiking in, along with the beneficial bacteria that you intended, cause that's just how life often works.

 

[katabasis]

... treat WITH caution? Yes?

I agree. Dicey and somewhat risky .... who knows what's hitchiking in, along with the beneficial bacteria that you intended, cause that's just how life often works.

What a typo, lol! Edited my post to fix.

 

[YippeeKi YOW !!]

What a typo, lol! Edited my post to fix.

You're speaking to the absolute Queen of Typos, which might be why I can spot them fairly quickly, you know, due to infinite depth of training .....

 

[Rufous McKinney]

I wouldn't just put the pill in your rectum; you'd probably want to make a suspension of the capsule's content in sterile saline and then use a syringe (minus the needle obviously) to administer it.

definately ....dilute dilute

I don' t understand what causes SIBO. And taking probiotics sounds really risky for introducing something to the wrong location.

 

[JES]

I'm curious and a bit skeptical about these specific strains. Probiotic makers love to sell lactobacillus and bifidobacterium probiotics. That is what you find on the market shelf in hundreds of different combos and with lots of different health claims about why their unique combo is better than other combos. One reason is because these species have quite long shelf-life, most of them do not require refrigeration and speaking of oral delivery, lactobacillus and bifidobacterium survive stomach acid quite well.

On the flip side, the problem with these probiotic types is that most are not human sourced, are not naturally found in human gut and do not colonize, so they basically leave your gut in a couple of days after taking them.

The other point I am skeptical about is whether these specific strains have anything special about them. The term "mood probiotic" unfortunately sounds a lot like marketing. I couldn't find evidence that Rosell-52ND and Rosell-175 have something unique about them that makes them impact your mood any more than other lactobacillus helveticus or bifidobacterium longum strains. In fact, it seems that the lactobacillus helveticus Rosell-52 strain is also known as lactobacillus acidophilus that has later been reclassified as lactobacillus helveticus. I suspect a lot of the probiotic mixes on the market already contain this strain and name it as lactobacillus acidophilus.

Another study here found no significant improvement in depression from lactobacillus helveticus and bifidobacterium longum combo. Are these the same strains? I don't know, but I would be cautious about some of these small-scale studies that supplement makers like to refer to in order to promote their product.

My personal experience is that most lactobacillus and bifidobacterium combos are rather similar in that they do not do much for my ME/CFS and increase certain immune symptoms a bit. Certain strains like lactobacillus reuteri and bifidobacterium infantis that are supposedly human sourced I had a bit success with. None of these produced anything as dramatic of an effect for me as for example taking e. coli probiotics like mutaflor, which do colonize the gut. Then again, I think FMT is an entirely other level and not even these probiotics can come close to the potential of it.

 

[YippeeKi YOW !!]

I'm curious and a bit skeptical about these specific strains.

Once you now the specific strain, which @katabasis has provided for us in one of his posts, above, you can easily google them and determine how much testing was done of them, what their sourcing was, etc ....

Another study here found no significant improvement in depression from lactobacillus helveticus and bifidobacterium longum combo.

Again, what strain of those were used in the study? It can make a huge difference. How many participants in that study? Was it blind, double blind, or open? Who FUNDED the study (this one is particularly important in terms of determining the study's reliability), and what are their academic or other affiliations?

My personal experience is that most lactobacillus and bifidobacterium combos are rather similar in that they do not do much for my ME/CFS and increase certain immune symptoms a bit.

Which strains of each did you use?

 

[katabasis]

On the flip side, the problem with these probiotic types is that most are not human sourced, are not naturally found in human gut and do not colonize, so they basically leave your gut in a couple of days after taking them.

The lack of longevity for certain probiotic species is definitely a concern, but perhaps one which merely divides between species which confer a long-lasting benefit after a single, limited course, and those whose benefit lasts only so long as intake is sustained. The latter situation is not ideal, but may still be perfectly feasible for such a readily available probiotic. It may also be the case that even if a probiotic species does not survive after administration is stopped, it may have produced biochemical changes in the gut (or elsewhere) that are more long-lasting.

The other point I am skeptical about is whether these specific strains have anything special about them. The term "mood probiotic" unfortunately sounds a lot like marketing. I couldn't find evidence that Rosell-52ND and Rosell-175 have something unique about them that makes them impact your mood any more than other lactobacillus helveticus or bifidobacterium longum strains.

"Mood probiotic" is definitely a marketing term, but that does not necessarily mean it is inaccurate.

As far as I can tell, you are correct that there is no evidence that specifically distinguishes between these probiotic strains and other strains of the same species. However, there are frequently major differences among strains of the same species - consider the results of "Strain-Specificity and Disease-Specificity of Probiotic Efficacy: A Systematic Review and Meta-Analysis", for example.

Of course, I would love to see either a head-to-head comparison, or some sort of explanation from Lallemand/Rosell Institute on the strain-specific properties. Perhaps this information will get out if this particular combination of strains gets more clinical study traction.

In fact, it seems that the lactobacillus helveticus Rosell-52 strain is also known as lactobacillus acidophilus that has later been reclassified as lactobacillus helveticus. I suspect a lot of the probiotic mixes on the market already contain this strain and name it as lactobacillus acidophilus.

For what it's worth, the original strain would have likely been labeled L. acidophilus Rosell-52. Even though the species name was changed (and I understand it, this is not uncommon in biology), the organism in question was still a very specific strain. I imagine most probiotic brands would specify this - why else would they buy the prestigious Rosell strains to begin with? It seems unlikely for this strain to show up incognito.

Another study here found no significant improvement in depression from lactobacillus helveticus and bifidobacterium longum combo. Are these the same strains? I don't know, but I would be cautious about some of these small-scale studies that supplement makers like to refer to in order to promote their product.

I looked up the trial registration and it does seem like the same strains are indeed being used in the study you linked. Which of course is disappointing, though ideally we'd see multiple studies to account for differences in population sampling, and any number of other variables that aren't fully controlled for.

That said, my main interest in this strain is not in its purported mood-improving properties, but in its specific effects on the HPA axis. Do those HPA axis effects play a role in the pathogenesis of depression? Maybe so, maybe not. In any case, the questionable success of these probiotic strains in treating depression ought not to bear strongly on their potential application in ME/CFS.

 

[Rufous McKinney]

That said, my main interest in this strain is not in its purported mood-improving properties, but in its specific effects on the HPA axis.

wanted to let you know I GOT the brand and am starting. (I was afraid I lost the thread..I have a hard time finding them again sometimes)

My current N=1 is adding alot more Omegas....and more purple anthocyanin; and a nattokwinase about every three days. (trying to get the blood flowing...)

I'm neither depressed nor anxious, until I find myself anxious or depressed!

Since I haven't messed with probiotics for a while now, I decided this sounded like I should give it a try.

 

[katabasis]

wanted to let you know I GOT the brand and am starting. (I was afraid I lost the thread..I have a hard time finding them again sometimes)

My current N=1 is adding alot more Omegas....and more purple anthocyanin; and a nattokwinase about every three days. (trying to get the blood flowing...)

I'm neither depressed nor anxious, until I find myself anxious or depressed!

Since I haven't messed with probiotics for a while now, I decided this sounded like I should give it a try.

Sounds good, I hope it works for you! Let me know how it ends up turning out.

I also take a high dose of omega 3s, but it's unclear whether it had any benefit for me. I've been curious to try nattokinase too (Dr. Levine has discussed with me the possible role of clotting problems in CFS symptoms), especially since really hot showers seem to at least temporarily alleviate some of the pain. But one thing at time, and I have a long list, lol.

 

[Rufous McKinney]

Sounds good, I hope it works for you! Let me know how it ends up turning out.

mostly I do chinese herbs, and my herbalist isn't big on probiotics and I was always a bit suspect.

I was in a really good mood yesterday on the day I took the first one: miracle result. (coincidence)

I also take a high dose of omega 3s, but it's unclear whether it had any benefit for me

I don't....and I don't eat hardly any fish either. so my sudden beefing that way up (via food and supplement) is I think helping my eye a bit (the dryness)

 

[Rufous McKinney]

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.

Update: I've taken the probiotic about six times...in 10 days. Noticed immediately, bowels firm up.

Noticed the following:

colon/digestion: slowed down dramatically but I feel very HEAVY

(I'm not used to this heavy feeling...I have fairly loose stools normally so this has transformed them to much firmer.) (I'm hoping maybe this is a temporary adjustment and my intestines will get more used to it....)

I STRETCHED really big this morning. Stretching is a reaction my body no longer does. (I don't yawn any more, either)

I can't tell what going on with other aspects as I've been rather crashed much of the week, complicating matters.

I"m doing nattokwinase one day, probiotic the next. Rinse repeat. The natto- noticeably improves my lungs. But is presumably moving some protein/toxins out...which may be why I"m easily crashing.