Uncommon Gut Bacteria May Be Linked to Restless Legs Syndrome

Summary: A small preliminary study suggests a possible link between small intestinal bacterial overgrowth (SIBO) and restless legs syndrome (RLS).

Source: American Academy of Sleep Medicine

Small intestinal bacterial overgrowth (SIBO) may be more common in people with restless legs syndrome (RLS), according to preliminary results from a small observational study.

The study found SIBO in all seven participants diagnosed with RLS who completed the protocol. By comparison, SIBO prevalence in the general population is typically estimated at no more than 15%.

“We observed very high rates of small intestinal bacterial overgrowth in the RLS group,” said lead author Daniel Jin Blum, Ph.D., D.B.S.M., adjunct clinical instructor at the Stanford Center for Sleep Sciences and Medicine in Redwood City, California. “Exploring the relationship between RLS and gut microbial health could open new avenues for earlier detection, prevention and potentially novel treatments for RLS and related sleep disorders.”

“Exploring the relationship between RLS and gut microbial health has the potential to open novel avenues for possible detection, prevention and treatment for RLS and other sleep disorders.”

SIBO is a condition in which bacteria that are normally rare in the small intestine become over-represented. Restless legs syndrome (RLS) is a sensorimotor disorder characterized by a strong, often irresistible urge to move the legs, frequently accompanied by uncomfortable sensations. Symptoms typically begin or worsen during periods of rest or inactivity, improve with movement, and occur primarily in the evening or at night.

Brain iron deficiency is a well-established risk factor for RLS. The study authors note that low iron in the brain may arise from insufficient dietary iron or from gut inflammation that interferes with iron absorption and metabolism.

Study procedures included validated questionnaires about sleep quality and SIBO symptoms, a take-home fecal collection kit, and a SIBO breath test kit. Fecal specimens were analyzed for microbial composition at the University of Minnesota Genomics Center using 16S rRNA gene sequencing protocols, while breath samples were analyzed by Aerodiagnostics to detect abnormal hydrogen and methane levels indicative of SIBO.

Low iron in the brain is a key risk factor for RLS. According to the authors, this brain iron deficiency may be secondary to dietary iron deficiency or, potentially, gut inflammation. The image is in the public domain.

Recruitment of additional participants is ongoing at the Stanford Sleep Center. Planned further analyses will compare fecal microbial composition across groups, explore subtypes of RLS associated with iron deficiency, and include comparisons with insomnia control participants to better understand specificity of findings.

Funding: This work was supported by a Pau Innovation Gift Fund Seed Grant.

The research abstract was published in an online supplement of the journal Sleep and was scheduled for presentation at SLEEP 2019, the 33rd annual meeting of the Associated Professional Sleep Societies LLC (APSS), organized by the American Academy of Sleep Medicine and the Sleep Research Society.

About this neuroscience research article

Source:
American Academy of Sleep Medicine
Media Contact:
Corinne Lederhouse – American Academy of Sleep Medicine
Image Source:
The image is in the public domain.

Original Research: Open access
“Restless Leg Syndrome: Does It Start With A Gut Feeling?” Daniel J Blum, PhD; Emmanuel During, MD; Fiona Barwick, PhD; Polina Davidenko, MS; Jamie M Zeitzer, PhD. Sleep. DOI: /10.1093/sleep/zsz067.008

Abstract

Restless Leg Syndrome: Does It Start With A Gut Feeling?

Introduction
Recent research increasingly links gut microbial health with sleep and sleep disorders. Restless legs syndrome (RLS) is one disorder where the microbiome may play a role. Although the exact pathogenesis of RLS remains incompletely understood, a relative deficiency of iron in the brain has been documented in patients and is associated with alterations in neurotransmitter systems such as adenosinergic, glutamatergic and dopaminergic pathways. Insufficient iron could reflect poor dietary intake or impaired absorption related to gut inflammation. The investigators hypothesized that small intestinal bacterial overgrowth (SIBO), a form of gut dysbiosis in which bacteria normally rare in the small intestine become overrepresented, could be associated with RLS and partly explain variability in serum iron availability among patients.

Methods
Participants were recruited at the Stanford Sleep Center into three groups: (1) RLS with low peripheral iron stores (<50 ng/mL and/or transferrin saturation <18%), (2) RLS with normal peripheral iron stores, and (3) insomnia controls. Participants completed questionnaires on sleep and SIBO symptoms and received home kits for fecal collection and SIBO breath testing. Fecal samples underwent microbial community profiling using 16S rRNA gene sequencing at the University of Minnesota Genomics Center. Breath samples were analyzed for hydrogen and methane using standardized protocols.

Results
To date, seven participants with RLS (three men and four women) completed the study protocol. All reported poor sleep quality (PSQI ≥ 5) and moderate to severe RLS symptoms (IRLS scores 13–34 out of 40). SIBO was detected in all seven participants (100%), a rate substantially higher than commonly reported population estimates of 6–15%.

Conclusion
These preliminary data indicate that SIBO may be more prevalent among people with RLS. Ongoing recruitment and planned analyses will further characterize fecal microbial composition, examine links with iron-deficiency subtypes of RLS, and compare findings with insomnia controls to evaluate whether the association is specific to RLS.

Support
Pau Innovation Gift Fund Seed Grant

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