Probiotic normalization of systemic inflammation in siblings of type 1 diabetes patients: an open-label pilot study
Abstract 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 susceptibilit...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-02-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-07203-6 |
| _version_ | 1818915664216195072 |
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| author | Susanne M. Cabrera Alison T. Coren Tarun Pant Ashley E. Ciecko Shuang Jia Mark F. Roethle Pippa M. Simpson Samantha N. Atkinson Nita H. Salzman Yi-Guang Chen Martin J. Hessner |
| author_facet | Susanne M. Cabrera Alison T. Coren Tarun Pant Ashley E. Ciecko Shuang Jia Mark F. Roethle Pippa M. Simpson Samantha N. Atkinson Nita H. Salzman Yi-Guang Chen Martin J. Hessner |
| author_sort | Susanne M. Cabrera |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-20T00:05:52Z |
| format | Article |
| id | doaj.art-ad250eba8213477aa74556a077af8614 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-20T00:05:52Z |
| publishDate | 2022-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-ad250eba8213477aa74556a077af86142022-12-21T20:00:40ZengNature PortfolioScientific Reports2045-23222022-02-0112111510.1038/s41598-022-07203-6Probiotic normalization of systemic inflammation in siblings of type 1 diabetes patients: an open-label pilot studySusanne M. Cabrera0Alison T. Coren1Tarun Pant2Ashley E. Ciecko3Shuang Jia4Mark F. Roethle5Pippa M. Simpson6Samantha N. Atkinson7Nita H. Salzman8Yi-Guang Chen9Martin J. Hessner10The Max McGee Research Center for Juvenile Diabetes, Children’s Research Institute of Children’s WisconsinThe Max McGee Research Center for Juvenile Diabetes, Children’s Research Institute of Children’s WisconsinThe Max McGee Research Center for Juvenile Diabetes, Children’s Research Institute of Children’s WisconsinThe Max McGee Research Center for Juvenile Diabetes, Children’s Research Institute of Children’s WisconsinThe Max McGee Research Center for Juvenile Diabetes, Children’s Research Institute of Children’s WisconsinThe Max McGee Research Center for Juvenile Diabetes, Children’s Research Institute of Children’s WisconsinDivision of Quantitative Health Sciences, Department of Pediatrics, Medical College of WisconsinCenter for Microbiome Research, Medical College of WisconsinCenter for Microbiome Research, Medical College of WisconsinThe Max McGee Research Center for Juvenile Diabetes, Children’s Research Institute of Children’s WisconsinThe Max McGee Research Center for Juvenile Diabetes, Children’s Research Institute of Children’s WisconsinAbstract 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.https://doi.org/10.1038/s41598-022-07203-6 |
| spellingShingle | Susanne M. Cabrera Alison T. Coren Tarun Pant Ashley E. Ciecko Shuang Jia Mark F. Roethle Pippa M. Simpson Samantha N. Atkinson Nita H. Salzman Yi-Guang Chen Martin J. Hessner Probiotic normalization of systemic inflammation in siblings of type 1 diabetes patients: an open-label pilot study Scientific Reports |
| title | Probiotic normalization of systemic inflammation in siblings of type 1 diabetes patients: an open-label pilot study |
| title_full | Probiotic normalization of systemic inflammation in siblings of type 1 diabetes patients: an open-label pilot study |
| title_fullStr | Probiotic normalization of systemic inflammation in siblings of type 1 diabetes patients: an open-label pilot study |
| title_full_unstemmed | Probiotic normalization of systemic inflammation in siblings of type 1 diabetes patients: an open-label pilot study |
| title_short | Probiotic normalization of systemic inflammation in siblings of type 1 diabetes patients: an open-label pilot study |
| title_sort | probiotic normalization of systemic inflammation in siblings of type 1 diabetes patients an open label pilot study |
| url | https://doi.org/10.1038/s41598-022-07203-6 |
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