The merry-go-round of symptom suppression in POTS, ME/CFS and Long COVID
- Rachel Jessey
- Dec 20, 2025
- 7 min read
Almost 16 years into clinical practice, it becomes clear that medication and supplements can move the needle in relation to symptom management in complex patients. PPIs, H2 blockers, mast cell stabilisers, and prokinetics can deliver clinically meaningful relief of gastrointestinal disorders for complex conditions like ME/CFS, Long Covid and POTS, particularly when reflux, upper GI pain and nausea are driving a significant proportion of the symptom burden. Yet the longer a case is followed, the more visible the trade‑offs become, with symptom control on one side, and on the other, a slow drift towards further dysmotility, microbiome disruption and persistent gastrointestinal symptoms that cannot be explained by the gut in isolation.
Patients presenting with complex chronic health conditions rarely present with a straightforward “acid problem” or simple IBS; their reflux, bloating and constipation are emerging within a context of autonomic imbalance, altered vagal tone and enteric nervous system stress. Medication can temporarily suppress the most distressing symptoms, but without addressing the upstream autonomic and ENS dysregulation, the physiology that predisposes to dysmotility and overgrowth remains in place.
Blood flow is one of the under‑appreciated parts of this story. The gut and the enteric nervous system are "hungry" tissues, drawing up to a quarter of cardiac output at rest and acting as a major vascular reservoir during postural change and after meals. In POTS and related dysautonomias, low or labile blood pressure, disordered vasomotor tone and excessive splanchnic pooling can mean that the enteric nervous system and intestinal wall do not receive consistent perfusion, particularly on standing or in the post‑prandial window. Over time, this combination of under‑perfusion in some phases and exaggerated pooling in others is a plausible contributor to impaired motility patterns.
In other words, the “gut issues” in ME/CFS, Long Covid and POTS are rarely gut‑only phenomena, they sit at the crossing point of medication effects, autonomic nervous system instability and enteric circuitry that is being asked to function under chronic haemodynamic stress.
So this is how I arrived at the question: do stomach acid suppressors, while initially helpful for symptom relief, ultimately create a merry‑go‑round of symptom suppression and deeper dysregulation in the system?
Dysmotility and proton pump inhibitor use do more than increase the odds of bloating and “IBS‑like” discomfort; they set the stage for a deeper disturbance in gut ecology that becomes highly relevant once autonomic dysfunction, POTS, ME/CFS or Long Covid enter the frame. When the enteric nervous system and the broader brain–gut axis are already under strain, adding impaired motility and long‑term acid suppression can create a double hit that amplifies small intestinal bacterial and fungal overgrowth, with consequences far beyond the digestive tract.
The Jacobs et al. study is often cited for one key message: in a cohort of 150 people with persistent, unexplained gastrointestinal symptoms, both small bowel dysmotility and PPI use independently increased the risk of small intestinal bacterial overgrowth (SIBO) and/or small intestinal fungal overgrowth (SIFO). Around two‑thirds of the group had objectively confirmed overgrowth on duodenal aspirate culture, despite non‑specific, overlapping symptom profiles that could not reliably distinguish those with SIBO/SIFO from those without. Dysmotility was defined rigorously using 24‑hour antro–duodeno–jejunal manometry, absent or abnormal migrating motor complexes, blunted post‑prandial responses, reduced phasic activity and impaired antrum–duodenum coordination—rather than inferred from symptoms alone.
As a piece of work, the study has several important strengths. It combines direct motility measurements with gold‑standard duodenal aspirate cultures, rather than relying on breath testing alone, and it includes both bacterial and fungal overgrowth, which better reflects what is seen in complex clinical practice. The finding that dysmotility and PPI use each roughly doubled the odds of overgrowth, without an additive effect when combined, reinforces that they are parallel, mechanistically distinct risk factors converging on the same problem: impaired clearance and altered luminal milieu in the proximal small bowel.
It is also clinically sobering that symptom patterns were poor predictors of who had overgrowth, underscoring the limitations of “symptom‑driven” SIBO/SIFO diagnoses and the value of objective testing where possible.
At the same time, there are limitations that matter when translating the paper into real‑world, dysautonomia‑heavy populations. The cohort consisted of patients with chronic unexplained GI symptoms after negative endoscopy and imaging; it was not enriched for those with POTS, ME/CFS or Long Covid, and autonomic parameters were not characterised. That means the study cannot tell us how much autonomic dysfunction modifies the relationship between motility, PPI exposure and overgrowth, or whether the same odds ratios hold in those with small fibre neuropathy, hypovolaemia, or viral‑triggered dysautonomia, all of which are now well‑described in ME/CFS and Long Covid. The use of manometry and duodenal aspirates, while methodologically robust, also limits generalisability because these tools are rarely available outside specialised centres, and the chosen cut‑offs for colony counts, though justifiable, remain an area of debate in SIBO/SIFO diagnostics.
Where this paper becomes particularly interesting is when it is read through the lens of autonomic and enteric nervous system disruption. In POTS, ME/CFS and Long Covid, a high proportion of patients exhibit autonomic imbalance, altered splanchnic blood flow, and evidence of small fibre neuropathy affecting visceral innervation. Gastrointestinal autonomic dysfunction can manifest as delayed gastric emptying, impaired small bowel motility, and disturbed migrating motor complexes, precisely the kind of patterns that, in Jacobs’ cohort, were associated with a two‑to three‑fold increase in SIBO/SIFO risk. At the same time, Long COVID, ME/CFS, POTS and related dysautonomias often drive high use of PPIs or H2 blockers, either for true reflux or for dyspeptic symptoms that are, in part, downstream of autonomic dysregulation. The result is a convergence of risk factors, impaired motility from enteric and autonomic dysfunction, plus an altered acid barrier from chronic stomach acid suppression therapy, both of which independently tilt the small bowel towards overgrowth and low‑grade inflammation.
Layered on top of this is the broader gut-brain axis. Long Covid and ME/CFS are now recognised as conditions characterised not just by dysautonomia, but by central and peripheral neuroinflammation, immune dysregulation and persistent metabolic stress, all of which feed back onto gut function.
Studies have documented shifts in the gut microbiome in both conditions, including reductions in butyrate‑producing and GABA‑modulating species, linking microbial ecology to autonomic tone, pain processing and fatigue. In that context, SIBO and SIFO are unlikely to be isolated to the gut alone, they are amplifiers in a loop where brain, enteric nervous system and immune system are already dysregulated. Impaired motility slows clearance, altered pH and bile dynamics favour different organisms, and the resulting dysbiosis and barrier disturbance send continuous afferent signals back to the brain, perpetuating autonomic instability and symptom load.
For clinicians working with POTS, ME/CFS and Long Covid, the practical implication is not that every patient needs duodenal aspirates or that PPIs on H2 blockers must be abandoned at all costs. Rather, this paper is a reminder to ask three specific questions.
First, is there objective or at least strong circumstantial evidence of dysmotility in this patient, and could that be a consequence of their autonomic or enteric neuropathy rather than just “IBS”?
Second, has short term stomach acid suppression drifted from initial symptom control into chronic maintenance without re‑evaluation, thereby adding avoidable risk to an already vulnerable small bowel ecosystem?
Third, if SIBO or SIFO is suspected, can testing be used judiciously to clarify the picture, given that symptoms alone are unreliable and that treating presumed overgrowth without acknowledging other mechanisms often leads to relapse.
So how can patients be meaningfully supported in this kind of complex picture? It starts, unglamorously, with a careful history and a genuinely thorough work‑up. When gastrointestinal symptoms sit alongside loss of taste and smell, reduced saliva, difficulty chewing or swallowing, gastroparesis and clear dysautonomia, the pattern points away from an isolated gut problem and towards a significant neurological interplay. In that context, no amount of stomach acid suppression is going to “fix” the issue, because the primary disruption lies in the autonomic and enteric control of the tract, not just in acid production.
What is needed instead is a broader strategy to stabilise and support the nervous system. Practices that gently stimulate the vagus nerve, such as humming or gargling, can be surprisingly useful additions, particularly when coupled with work on blood volume, blood pressure and splanchnic blood flow so that the gut and its intrinsic nervous system are better perfused during daily life. Nutritional management, pacing of meal size and timing, and, where appropriate, targeted supplementation form part of the same scaffold as well as retraining circadian rhythms and ensuring that your eyes and skin are exposed to appropriate daytime and night time signalling. Rifaximin is frequently prescribed in SIBO‑like presentations and can reduce bacterial load, but without addressing the underlying motility and autonomic mechanisms, relapse rates are high and symptoms often flare soon after treatment stops.
What really matters here is accepting that there is no quick fix, no single protocol and no off‑the‑shelf diet that will reliably solve this kind of case. With careful examination of the history, a thorough work‑up and genuinely tailored interventions, however, the chances of achieving sustainable, long‑term improvement increase dramatically.
For readers who want to look at the paper directly, it is available here: Jacobs C, Coss Adame E, Attaluri A, Valestin J, Rao SS. Dysmotility and proton pump inhibitor use are independent risk factors for small intestinal bacterial and/or fungal overgrowth. Alimentary Pharmacology & Therapeutics. 2013 Jun;37(11):1103–1111.
Comments