Introduction and objective:
A number of studies indicate the presence of a thyroid-gut axis and the important influence of the gut microbiota on thyroid function. As prebiotics, probiotics and synbiotics show therapeutic potential in the treatment of intestinal dysbiosis, the aim of this review is to evaluate the efficacy of their supplementation in primary thyroid diseases.

Review methods:
Electronic databases (Ovid MEDLINE, Embase, CENTRAL), registers of clinical trials, and grey literature up to 6 October 2022 were searched for randomised controlled trials (RCTs) meeting pre-specified inclusion criteria. The protocol was registered in PROSPERO (CRD42021235054).

Brief description of the state of knowledge:
After screening 1,721 references, two RCTs were identified, which included 136 hypothyroid participants in total. Meta-analysis of the results after eight weeks of supplementation with predominantly Lactobacillus and Bifidobacterium strains indicated a clinically and statistically nonsignificant decrease in TSH (MD –0.19 mIU/L; 95% CI –0.43 to 0.06; I2= 0%), and no effect on fT3 levels (MD 0.01 pg/mL; 95% CI–0.16 to 0.18; I2= 0%). Data from single studies indicated no significant change in the levels of fT4, thyroid auto-antibodies, BMI, levothyroxine doses, and severity of symptoms measured with validated scales. Only constipation scores showed significant improvement (MD –8.71 points in the Faecal Incontinence Questionnaire; 95% CI –15.85 to –1.57; I2= 0%).

Low-certainty evidence from two randomised trials, suggests that routine administration of probiotics, prebiotics or synbiotics may result in little to no benefit in patients with primary hypothyroidism.

The authors express their thanks Dr. Giorgia Spaggiari and Prof. Daniele Santi from the Department of Biomedical, Metabolic and Neural Sciences at the University of Modena and Reggio Emilia, Modena; Prof. Gholamreza Askari and Ms. Sepide Talebi from the Food Security Research Centre and Department of Community Nutrition, School of Nutrition and Food Science, University of Medical Sciences, Isfahan, as well as Dr. Mario Salvi from the Graves’ Orbitopathy Centre, Endocrinology, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milan, for providing additional information concerning their studies.
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