The Gut Microbiota in Patients with Polycythemia Vera is Distinct from that of Healthy Controls and Varies by Treatment

[Manouche]

 »Recombinant interferon-α2 (IFN) treatment of patients with PV has been shown to be disease-modifying in terms of normalization of elevated blood cell counts in concert with a reduction in the JAK2V617F allelic burden. Therefore, we hypothesized that patients treated with IFN might have a composition of the gut microbiota towards normalization… Furthermore, we report the composition of the gut microbiota to differ between the treatment groups (IFN, hydroxyurea, no treatment, combination therapy with IFN and ruxolitinib) and the HCs. The observations are highly interesting considering the potential pathogenetic importance of an altered gut microbiota for development of other diseases, including chronic inflammatory diseases. »

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[Aldebaran25]

This is very, very interesting. I suffer from another condition, cutaneous sarcoidosis, which is a systemic inflammatory disease. Being in the process of moving from HU to Peg, I need to keep a close watch on the sarcoid as it could get worse with Peg (that is the general understanding but the experience is limited as there aren't many cases of both PV and sarcoid). I now hope that Peg may actually help normalise the gut microbiote and maybe, down the road, help keep the sarcoid at bay. It may be a bit optimistic but hope is free!

[Bluetop]

Thanks for posting. I wonder if it is the medication which causes the changes in microbiome. I do include things like kefir in my diet...no idea if it helps or not! Certainly it would be interesting to see more research in this area.

[hunter5582]

Very interesting. My current MPN Specialist at Johns Hopkins , Dr. Jain, is doing a similar study. I will be participating in the study. Hopefully we will all learn more about this important topic.

When I was on HU it caused chronic constipation. When I looked into why, I found two references. HU can compromise the intestinal endothelium. HU also has antibiotic properties that could theoretically compromise the intestinal microbiome.

The intestinal microbiome is vital to health. The notion that it may play a role in PV pathogenesis makes sense and is worth investigation. The impact of various forms of treatment on the microbiome is also worth investigation. I altered my diet to include more natural probiotic and prebiotic foods. I also take a daily probiotic supplement. Hard to prove that is actually helps, but I figure that there is enough support for the value of a healthy microbiome that it is worth doing. My Integrative medicine doc concurs.

Thanks for posting the information.

[souplover in reply to hunter5582]

Hunter, I'm not able to access the full article. When you say pathogenesis, they're referring to the course of the illness, not the origin, correct?

I'm on Hydroxyurea and have developed lactose intolerance and other intestinal issues over the last two years or so. Both my hematologist and gastroenterologist were dismissive of a connection between the digestive issues and the hydroxyurea. But it makes sense to me.

Please do continue to share on this topic! I bet others are struggling with this too.

[hunter5582 in reply to souplover]

Pathogenesis = "the manner of development of a disease." What I was referring to is that inflammation plays a significant in the development of PV. The link between the microbiome of the gut and inflammation is well established. There is thinking now that inflammation plays a significant role in the progression of MPNs as it does in other cancers. Systemic inflammation also impacts the GI system. The JAK2 mutation causes systemic inflammation. The body, including the intestinal microbiome, is a complex interactive system. It is a bit of a chicken and egg question. Which comes first? I suspect it will turn out to be some kind of feedback loop. Only time, and research, will tell.

It is interesting that you note lactose intolerance. HU contains lactose. I seem to recall you have posted about this before. The impact of HU on the GI system is well established. It seems plausible to me that it could cause a variety of GI problems, perhaps including lactose intolerance, even if it is a rare side effect. There does not seem to be a lot about this but there is this reference. I think you have seen this before. ehealthme.com/ds/hydroxyure...

The GI problems were one of the reasons I discontinued HU. If you feel that the adverse effects of HU are not worth the benefits, there are other treatment options. You can review those options with your care team if you believe it to be in your best interest.

Do please continue to post about your experience. Others can benefit from what you learn.

[souplover in reply to hunter5582]

Interesting. What I'm seeing is that in fact lactose intolerance is NOT a very widely reported side effect.

I consulted with a nutritionist, who said that the hydroxyurea could alter the microbiome, which in turn, could lead to digestive problems. Seems like the study that Manouche posted is saying the same, no? Unless I'm misunderstanding the abstract.

[hunter5582 in reply to souplover]

There is likely more to be found on this topic, but here is one reference about the antibiotic properties of HU. sciencedaily.com/releases/2...

The gut depends on healthy bacteria that antibiotics kill. That is why antibiotics can case GI problems. What the nutritionist is saying and what is referenced in the article about HU impact on the gut are consistent with this.

The bottom line is that we always have to do a risk/benefit analysis on each of our treatment options. We each react differently to each of the treatment options. Our awareness of how the medications work, what the benefits and risks are, and what adverse effects are tolerable/acceptable allow us to work with our care team to make good plans. We have rare diseases and sometimes deal with rare side effects from the medications we use. It is complex and sometimes the answers are not clear. Sometimes we just have to use out best judgment and make the best decisions we can.

All the best.

[souplover in reply to hunter5582]

Thank you so much! What treatment did you switch to - and how have you found the treatment you switched to in terms of side effects and efficacy?

[hunter5582 in reply to souplover]

The big switch on the Western medicine side was to Besremi. It has been a very good choice for me.

On the complementary health side, I was already using curcumin on the advice of my rheumatologist to manage osteoarthriitis. It works better than any NSAID I ever took and is certainly safer in conjunction with aspirin. The Integrative medicine doc recommend two other things. SPM Active (a proresolving mediator) and L-Glutathione. I had asked about N-Acetylcysteine since there is evidence in the literature about NAC. The doc said that the benefit of NAC is that it is the precursor to L-Glutathione. Therefore, just go straight to the L-Glutathione.

In addition, the doc did a complete nutritional analysis. I was Vit, D, Vit B/Folate, and Magnesium deficient. This despite a very healthy diet. I now take supplements for these deficiencies and we measured the response to titrate the doses. In addition, we found a significant level of mercury in my system. I had been eating a good bit of high-mercury seafoods. Eliminating tuna (and other high-mercury seafood) from my diet and a liver cleanse cleared the problem up.

The benefit of Integrative/Functional Medicine is the holistic approach. The body is an integrated system. We need to consider all aspects of body function and maintain good overall health. Nutrition matters and is often ignored. Controlling systemic inflammation matters and is often ignored. Including a provider who is skilled in these areas on our care team is very useful. Combining Western medicine with complementary health can be very effective, but it needs to be done in consultation with a qualified care team.

Hope that helps.

[EPguy in reply to hunter5582]

I looked into the lactose issue in some detail on another thread. It seems not a big worry for the more common " conventional" lactose intolerance since the amount is very small. Lactose is actually in many meds I found. But there can be less common reactions to this lactose, allergies and others.

[souplover in reply to EPguy]

Thanks so much, Hunter and EPguy. I do remember reading a post that the amount of lactose in HU is minute and unlikely to trigger a reaction.

I'll ask about Besremi and curcumin.