Probiotic normalization of systemic inflammation in siblings of type 1 diabetes patients: an open-label pilot study. Sci Rep 2022 Feb 28;12(1):3306
Date
03/02/2022Pubmed ID
35228584Pubmed Central ID
PMC8885673DOI
10.1038/s41598-022-07203-6Scopus ID
2-s2.0-85125563972 (requires institutional sign-in at Scopus site) 14 CitationsAbstract
The incidence of type 1 diabetes (T1D) has increased, coinciding with lifestyle changes that have likely altered the gut microbiota. Dysbiosis, gut barrier dysfunction, and elevated systemic inflammation consistent with microbial antigen exposure, have been associated with T1D susceptibility and progression. A 6-week, single-arm, open-label pilot trial was conducted to investigate whether daily multi-strain probiotic supplementation could reduce this familial inflammation in 25 unaffected siblings of T1D patients. Probiotic supplementation was well-tolerated as reflected by high participant adherence and no adverse events. Community alpha and beta diversity were not altered between the pre- and post-supplement stool samplings. However, LEfSe analyses identified post-supplement enrichment of the family Lachnospiraceae, producers of the anti-inflammatory short chain fatty acid butyrate. Systemic inflammation was measured by plasma-induced transcription and quantified with a gene ontology-based composite inflammatory index (I.I.com). Post-supplement I.I.com was significantly reduced and pathway analysis predicted inhibition of numerous inflammatory mediators and activation of IL10RA. Subjects with the greatest post-supplement reduction in I.I.com exhibited significantly lower CD4+ CD45RO+ (memory):CD4+ CD45RA+ (naïve) T-cell ratios after supplementation. Post-supplement IL-12p40, IL-13, IL-15, IL-18, CCL2, and CCL24 plasma levels were significantly reduced, while post-supplement butyrate levels trended 1.4-fold higher. Probiotic supplementation may modify T1D susceptibility and progression and warrants further study.
Author List
Cabrera SM, Coren AT, Pant T, Ciecko AE, Jia S, Roethle MF, Simpson PM, Atkinson SN, Salzman NH, Chen YG, Hessner MJAuthors
Samantha N. Atkinson PhD Bioinformatics Analyst III in the Microbiology and Immunology department at Medical College of WisconsinSusanne M. Cabrera MD Associate Professor in the Pediatrics department at Medical College of Wisconsin
Yi-Guang Chen PhD Professor in the Pediatrics department at Medical College of Wisconsin
Alison T. Coren MD Assistant Professor in the Pediatrics department at Medical College of Wisconsin
Martin J. Hessner PhD Professor in the Pediatrics department at Medical College of Wisconsin
Nita H. Salzman MD, PhD Director, Professor in the Pediatrics department at Medical College of Wisconsin
Pippa M. Simpson PhD Adjunct Professor in the Pediatrics department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Diabetes Mellitus, Type 1Humans
Inflammation
Pilot Projects
Probiotics
Siblings
