A surprising herpesvirus virus shows up in fibromyalgia patients’ guts
However similar the symptom presentations of fibromyalgia (FM) and chronic fatigue syndrome (ME/CFS) are, their research pathways have been fairly distinct, with FM researchers focusing more on the central nervous system and ME/CFS researchers more on pathogens, the immune system, and energy production.
As time has gone on, though, the fields have started to coalesce a bit. It took years, for instance, for the small fiber findings in FM to filter down to ME/CFS, but they were recently documented in ME/CFS. Similarly, FM researchers have shown more interest in the immune system and orthostatic intolerance of late.
Pathogens, though, have remained almost entirely the province of ME/CFS research. While herpesvirus ME/CFS papers continue to pour out – one was published just last month – the number of herpesvirus FM studies, most of which date back decades, can be counted on the fingers of one hand.
All of which makes the herpes simplex virus type 1 (HSV-1) saga in fibromyalgia all the more inexplicable. For one, the herpesvirus Skip Pridgen MD has proposed is causing FM has been virtually ignored by both fields. Despite that fact, Pridgen has been able to do something for FM that no one in the ME/CFS field – despite decades of interest, and dozens and dozens of herpesvirus studies and papers – has been able to do: mount a large (n=460, 40+sites), rigorously controlled, trial of anti-herpes virus drugs. (The closest ME/CFS came to that was the single-site, 30-person Montoya valganciclovir trial in 2013). It’s an amazing thing.
Learn more about HSV-1…
A New Virus for Fibromyalgia (and ME/CFS?)
- Skip Pridgen’s assertion that herpesviruses may be causing fibromyalgia was – given that no one in 30 years had cared a darn about herpesviruses in FM in 30 years – was bad enough. If that seemed wild then Pridgen’s belief that herpes simplex virus-1 (HSV-1) was behind FM seemed beyond the pale given that no one in the herpesvirus-focused ME/CFS research field had given that virus a thought.
- This latest study, though, led by Carole Duffy, found that not only was active HSV-1 found in ALL the gut biopsies of FM patients with gut problems but that it was the ONLY herpes virus found.
- While other herpesviruses can infect the gut lining, HSV-1 is the only herpesvirus known to infect the neurons leading to the gut. Because HSV-1 can spread across the synapses of the neurons it can potentially affect many neurons and has been found to infect the trigeminal neurons in the face, among others. Pridgen has proposed that HSV-1 infects more than the gut in FM.
- The high rates of HSV-1 (80%) found in the biopsies of people with functional gastrointestinal disorders (gut disorders produced by problems with the gut-brain axis) suggested HSV-1 might be producing problems in people with mysterious gut issues (such as IBS, nausea, vomiting and many others). One possibility is that viral interference with gut-brain interactions is altering gut motility, affecting gut flora, etc.
- In contrast, the low rates of HSV-1 found in people with gut issues but who did not have a functional gastrointestinal gut disorder suggested HSV-1 was probably not causative.
- Since the study focused on gut biopsies from FM patients with gut issues we don’t know if the results apply to FM patients without these issues. We’ll find out more about that when the results of Pridgen’s big FORTRESS antiviral trial in FM are released in September. (That trial was not restricted to FM patients with gut issues).
- Virios, the company Pridgen started, has begun a trial of a similar product (valacyclovir/celexicob) in long COVID at the Bateman Horne Center in Salt Lake City.
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The study, led by University of Alabama virologist Carole Duffy, examined gastric biopsies from 30 people who met the criteria for having both a functional gastrointestinal disorder (FGID) and fibromyalgia, 15 people with an FGID but not with FM, and 15 control patients who had undergone an endoscopy for something other than a functional gut issues (GI bleed, anemia, hiatal hernia, cancer, etc.).
The Functional Gut Diseases
Functional gastrointestinal disorders (FGIDs) are generally characterized as disorders such as irritable bowel syndrome that impact functionality but for which no organic problem has been found. They’ve have been found in every part of the gastrointestinal system. The dozens of FGIDs that have been identified produce problems with belching, esophageal pain, vomiting, nausea, gallbladder issues, rectal pain, etc. Perhaps due to the complex nature of its internal nervous system – sometimes referred to as the “second brain” – the gut seems to be superb at producing mysterious forms of the disease.
Our understanding of FGID has been evolving over time, and the authors note that problems with gut motility (the timely passage of materials through the gut), damage to the gut lining, immune problems, and altered gut flora (microbiome) are now believed to contribute to them.
As to what causes them – anything that disturbs gut-brain communications or alters gut immune functioning, and/or dysregulates the neuroendocrine system could be responsible. At the top of that list are parasitic, bacterial, or viral infections. Of the viruses, the herpesviruses – most of which we never manage to completely eliminate – and which readily infect the gut and can certainly impact the neuroendocrine system, of course, loom large.
Several herpesviruses (EBV, varicella-zoster, cytomegalovirus) can infect the gut lining, but only HSV-1 has been able to make it to the neurons that innervate the gut. Once an infection there is established, any reactivation of the virus will cause the production of more virions which then attack the gut lining as well as gut-brain-neural pathways.
When Pridgen’s standard gut treatments for his FM patients produced a relapsing-remitting pattern – they got better and then relapsed – he suspected viruses were at play. The big surprise came when their gut and FM symptoms improved while on his antiviral combination. Pridgen believes the HSV-1 infection he’s found in the gut is just the tip of the iceberg.
The virus is best known for producing cold sores but can infect sensory nerves in the trigeminal ganglia in the face, the gut, and nerves that make up the gut-brain axis. The bug apparently first enters the body through the mouth and the throat, and makes it down to the gut when we swallow.
Animal studies have shown that HSV-1 infection of the major nerve leading to the gut (myenteric plexus) results in “functional and structural alterations of the enteric (or gut) nervous system”. Interestingly, the virus didn’t need to replicate to affect the gut – all it needed to do was emit a substance that attracted immune cells called macrophages to the gut. They then emitted free radicals that harmed the gut neurons responsible for gut motility – impairing that critical function.
Because the rate at which food substances pass through the gut affects the gut microflora, having low gut motility (constipation) or high gut motility (diarrhea) promotes harmful gut microflora growth. It’s possible that HSV-1 activated macrophages could be damaging and setting off nerves across the central nervous system.
As noted earlier, the study assessed the presence of pathogens in the red streaks found in the biopsies of the gut lining. HSV-1 DNA was detected in the biopsies of 100% of the FM patients with gut issues, 80% of the people with gut issues but not FM, and 27% of the people who were being assessed for something other than a functional gut disorder. Despite the fact that other herpesviruses are known to infect the gut lining, no other herpesviruses were found.
The authors reported that the virus was active; i.e. it was replicating and pumping out infectious forms of the virus. They noted that HSV-1 is a potent virus, which, because it’s able to spread from synapse to synapse in the neurons, could be involved in many forms of FGID. Indeed, HSV-1 is able to establish infection both in sympathetic and parasympathetic nerves leading to the gut, and in the complex nervous system (enteric nervous system) found in the gut itself that affects gut motility, digestive secretion, blood flows, etc.
The authors noted that the study was small and that corroborating serological (antibody) data needed to be gathered. They called for much larger studies to assess the intriguing connection between HSV-1, fibromyalgia, and other functional gastrointestinal disorders.
This is the first study in years, if at all, to find replicating herpesviruses in fibromyalgia, and, of course, adds HSV-1 to the list of herpesviruses to consider in ME/CFS (Pridgen believes a similar situation exists in that disease). Plus, it suggests HSV-1 may play a role in functional gut issues in people who don’t have FM.
Correlation, of course, isn’t causation. Because the study examined people with FM with gut issues, it may not reflect what’s going on in people with FM who don’t have those issues. Pridgen reported, though, that most FM patients in his experience met the criteria for being in this study, and he finds red streaks in about 85% of FM patients he does endoscopies in.
Simply finding these strange herpes viruses littering the gut tissues of FM patients is a significant finding. Since the virus can travel from nerve to nerve one wonders where else in the body it may be present. The fact that it lives in the sensory nerves suggests it could be causing all manner of strange symptoms – and strange symptoms – as anyone knows who has these diseases – are a hallmark of them.
Pridgen believes the virus may be present in the trigeminal ganglia in the head and neck, the nodose ganglia in the GI tract, the dorsal root ganglia near the spine which transfer sensory signals from across the body into the spinal cord, and less commonly, the brain. The possibility the virus is producing some pretty dramatic symptoms certainly seems present.
It makes one wonder just what is hiding out in the tissues of people with ME/CFS, and one would hope it will prompt similar studies. Are those red streaks present in ME/CFS patients’ guts as well? If they’re present in people with “functional gastrointestinal disorders” (which includes IBS) one would suspect they would be present in at least some people with ME/CFS as well.
We’ll know more about Pridgen’s effort to eliminate these viruses in FM when Virios’s big FORTRESS study winds up. Perhaps because he’s founded what looks like a pretty formidable company, Pridgen’s FORTRESS trial seems to be on track – a rarity in ME/CFS. Results from the 400+ person phase II FM trial of Virios’ famvir/celexicob combination should be available by September.
Virios is also beginning a trial of a formulation of valacyclovir/celexicob in long COVID with Dr. Lucinda Bateman at the Bateman Horne Center in Salt Lake City, Utah. Pridgen has stated he plans to move forward on drug trials in ME/CFS as well. We may see that pattern – drug trials moving from FM to ME/CFS – more often as the interest in FM moves more towards the immune system.
Find out more about ongoing fibromyalgia clinical trials including some possible game-changers here.
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