How Gut Bacteria Influence This Mysterious Disorder
Imagine standing up and suddenly feeling your heart race as if you're running a marathon, while your world spins with dizziness and fatigue. This is the daily reality for millions living with Postural Orthostatic Tachycardia Syndrome (POTS)1 3 , a complex form of autonomic nervous system dysregulation that predominantly affects young women1 3 .
What makes this condition particularly mysterious is its constellation of symptoms—ranging from heart palpitations and dizziness to gastrointestinal distress and severe fatigue—without clear visible signs. While the cardiovascular aspects of POTS have been studied for decades, researchers have recently begun investigating an unexpected potential contributor: the trillions of bacteria residing in the human gut. This exploration into the gut-brain-heart axis may hold keys to understanding this debilitating condition1 7 .
The gut microbiome, consisting of bacteria, archaea, viruses, and fungi, plays a crucial role in human health far beyond digestion. These microbial communities produce numerous bioactive compounds, including short-chain fatty acids (SCFAs) like acetate, propionate, and butyrate, which are created when gut bacteria ferment dietary fiber1 . These SCFAs can influence everything from immune function to neurotransmitter production, effectively creating a communication network between the gut and other body systems1 .
Gut bacteria produce neurotransmitters that influence brain function
SCFAs help regulate immune responses and inflammation
Gut metabolites can affect heart rate and blood pressure
The autonomic nervous system, which regulates involuntary bodily functions like heart rate and blood pressure, appears to be particularly influenced by gut-derived metabolites1 . This connection forms what scientists call the "gut-brain axis," which may extend to become a "gut-brain-heart axis" in the context of POTS. Given that POTS patients frequently experience gastrointestinal symptoms alongside their cardiovascular issues, researchers have begun to question whether gut dysbiosis (microbial imbalance) might contribute to the disorder's development or persistence7 8 .
To systematically investigate the potential connection between gut health and POTS, researchers at Vanderbilt University conducted a comprehensive comparison of gut microbiota and SCFA profiles between POTS patients and healthy individuals1 2 .
The research team recruited 48 participants—25 women with POTS and 23 healthy female controls—and implemented rigorous experimental procedures:
Participants underwent detailed cardiovascular assessment while supine and upon standing, confirming characteristic POTS responses including excessive heart rate increases and elevated circulating norepinephrine and epinephrine1 2 .
For two weeks before sample collection, all participants logged their food intake using the MyFitnessPal application, allowing researchers to account for dietary influences on gut microbiota1 .
Fecal samples were collected using specialized kits designed to stabilize genetic material. Researchers employed shotgun metagenomic sequencing (providing a comprehensive view of all genetic material in the samples) and careful DNA extraction protocols to characterize the gut microbiota1 4 .
Contrary to what the researchers might have expected, the study revealed more similarities than differences between the gut environments of POTS patients and healthy controls:
| Diversity Metric | POTS Patients | Healthy Controls | Statistical Significance |
|---|---|---|---|
| Alpha Diversity (Shannon Index) | Similar | Similar | Not Significant |
| Beta Diversity (Bray-Curtis) | Similar | Similar | Not Significant |
| Firmicutes to Bacteroidetes Ratio | Similar | Similar | Not Significant |
| Overall SCFA Levels | Similar | Similar | Not Significant |
Despite these overall similarities, the researchers noted intriguing trends at the genus level of bacterial classification:
| Bacterial Genus | Direction in POTS | Potential Significance |
|---|---|---|
| Lachnoclostridium | Increased | Previously associated with other neurological and inflammatory conditions |
| Coprococcus | Decreased | Known butyrate-producer with potential anti-inflammatory effects |
| Coprobacter | Decreased | Less studied genus, function not fully understood |
The dietary analysis revealed that both groups consumed similar amounts of calories, macronutrients, fiber, and even salt—the latter being particularly noteworthy since POTS patients are typically advised to consume high-salt diets to help maintain blood volume1 .
Perhaps most surprisingly, despite the KEGG metabolic pathway analysis (a method for predicting metabolic capabilities of microbial communities) suggesting potential differences in SCFA-related pathways, the actual measurements of short-chain fatty acids showed no significant differences between POTS patients and controls1 2 .
While the Vanderbilt study suggested limited microbial differences, more recent research has challenged this conclusion. A 2024 study published in Scientific Reports found significant alterations in gut microbiota composition in POTS patients compared to controls7 .
This larger investigation discovered several differences in taxonomic composition between POTS and controls, noting that "clinical variables total IBS-SSS, fatigue, and bloating and flatulence significantly correlated with multiple individual taxa abundances, alpha diversity, and functional abundances"7 .
Different approaches may explain conflicting results
The discrepancies between these studies highlight the complexity of microbiome research and suggest that factors like geographical differences, sample sizes, or methodological variations might influence outcomes.
Understanding how researchers study the gut microbiome helps appreciate both the possibilities and limitations of this evolving field:
| Method | Primary Function | Key Advantages | Limitations |
|---|---|---|---|
| Shotgun Metagenomic Sequencing | Comprehensive analysis of all genetic material in a sample | Identifies bacteria, viruses, fungi; assesses functional potential | Costly; complex data analysis; requires high-quality DNA4 6 |
| 16S rRNA Sequencing | Targets specific bacterial gene regions | Cost-effective; good for bacterial composition surveys | Limited resolution; misses non-bacterial microbes4 |
| Liquid Chromatography-Mass Spectrometry | Precisely identifies and quantifies metabolites like SCFAs | High sensitivity and specificity; can detect numerous compounds simultaneously | Requires specialized equipment; complex data interpretation1 |
| Fluorescence In Situ Hybridization (FISH) | Visualizes specific microbial populations within samples | Provides spatial information; allows cell counting | Lower throughput; limited to known targets4 |
Each method offers unique insights, and researchers often combine multiple approaches to overcome individual limitations and validate findings4 6 .
The investigation into the gut-POTS connection remains in its early stages. The subtle differences observed in the Vanderbilt study, while not dramatic, suggest that specific bacterial groups rather than overall community structure might be relevant to POTS1 . The contrasting results from the 2024 study further emphasize the need for additional research with larger, more diverse populations7 .
Future research should include more participants from diverse geographic locations to account for regional variations in gut microbiota.
Studies exploring whether modulating the gut microbiome through dietary changes could alleviate POTS symptoms.
Research into targeted probiotic supplements that might help restore microbial balance in POTS patients.
Understanding exactly how gut metabolites influence autonomic nervous system function in POTS.
Future studies may explore whether modulating the gut microbiome through dietary interventions, prebiotics, or probiotics could alleviate some POTS symptoms. The significant correlation between gastrointestinal symptoms and specific microbial patterns found in recent research suggests this might be a promising avenue7 .
For the millions living with POTS, this ongoing research represents hope—not just for better understanding what causes their symptoms, but for developing new approaches to treatment that address the condition from the ground up, beginning with the gut.