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Updated: Jun 2, 2026

Perturbations of Circulating miRNAs in Irritable Bowel Syndrome Detected Using a Multiplexed High-throughput Gene Expression Platform
Published on: November 30, 2016
Restless legs syndrome is associated with irritable bowel syndrome and small intestinal bacterial overgrowth
Leonard B Weinstock1, Arthur S Walters
1Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, USA. lw@gidoctor.net
Background:
Restless legs syndrome (RLS) is linked to gastrointestinal disorders. The prevalence of irritable bowel syndrome (IBS) and small intestinal bacterial overgrowth (SIBO) in RLS patients was determined.
Methods:
RLS subjects were recruited from unbiased ads that did not mention gastrointestinal symptoms. RLS diagnosis was confirmed by a neurologist and utilized the International RLS Study Group criteria. General population controls (GPC) were spouses of gastrointestinal clinic patients and were excluded for RLS. Completely healthy controls (CHC) were excluded for RLS and gastrointestinal symptoms. IBS was diagnosed by Rome II criteria. SIBO was diagnosed by the lactulose breath test (LBT).
Results:
There were 32 RLS subjects (23F/9M; 57 yo), 25 GPC (13F/12M; 58 yo) and 30 CHC (19F/11M; 44 yo). Twenty-nine had RLS unassociated with other GI diseases, one had celiac disease, and two had gastric resections. IBS was diagnosed in 28% of RLS subjects compared to 4% GPC (p=0.0317). SIBO was diagnosed in 69% of RLS subjects compared to 28% of GPC (p=0.0033) and 10% of CHC. Using a false positive rate of 10%, 59% of positive LBT results are associated with RLS.
Conclusions:
IBS and SIBO are common in RLS. Three hypotheses developed are (a) RLS patients are selectively immunocompromised or genetically predisposed and thus more subject to SIBO; (b) SIBO leads to autoimmune changes, and subsequent auto-antibodies attack brain and/or peripheral nerves and (c) SIBO inflammation leads to increased hepcidin and CNS iron deficiency which, in turn, leads to RLS. These hypotheses bear further investigation.
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