Multi-omic interactions in the gut of children at the onset of islet autoimmunity

Microbiome

Research

Emma E. Hamilton-Williams¹  Patrick G. Gavin²  Michelle M. Hill³  Ki Wook Kim⁴  Maria E. Craig⁵ 

[1] Frazer Institute, The University of Queensland, Woolloongabba, QLD, Australia;Frazer Institute, The University of Queensland, Woolloongabba, QLD, Australia;Present Address: Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Boston, MA, USA;Present Address: Harvard Medical School, Boston, MA, USA;QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia;Virology Research Laboratory, Prince of Wales Hospital Randwick, Sydney, Australia;School of Clinical Medicine, Discipline of Paediatrics and Child Health, Faculty of Medicine and Health, University of New South Wales, Sydney, Australia;Virology Research Laboratory, Prince of Wales Hospital Randwick, Sydney, Australia;School of Clinical Medicine, Discipline of Paediatrics and Child Health, Faculty of Medicine and Health, University of New South Wales, Sydney, Australia;Institute of Endocrinology and Diabetes, Children’s Hospital at Westmead, Sydney, Australia;Discipline of Child and Adolescent Health, University of Sydney, Sydney, Australia;

关键词: Gut microbiota;    Microbiome;    Metaproteome;    Virome;    Type 1 diabetes;    Islet autoimmunity;    Infant/child;    Faecalibacterium;    Mastadenovirus;   

DOI  :  10.1186/s40168-022-01425-6

 received in 2022-04-18, accepted in 2022-11-11,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundThe gastrointestinal ecosystem is a highly complex environment with a profound influence on human health. Inflammation in the gut, linked to an altered gut microbiome, has been associated with the development of multiple human conditions including type 1 diabetes (T1D). Viruses infecting the gastrointestinal tract, especially enteroviruses, are also thought to play an important role in T1D pathogenesis possibly via overlapping mechanisms. However, it is not known whether the microbiome and virome act together or which risk factor may be of greater importance at the time when islet autoimmunity is initiated.ResultsHere, we apply an integrative approach to combine comprehensive fecal virome, microbiome, and metaproteome data sampled before and at the onset of islet autoimmunity in 40 children at increased risk of T1D. We show strong age-related effects, with microbial and metaproteome diversity increasing with age while host antibody number and abundance declined with age. Mastadenovirus, which has been associated with a reduced risk of T1D, was associated with profound changes in the metaproteome indicating a functional shift in the microbiota. Multi-omic factor analysis modeling revealed a cluster of proteins associated with carbohydrate transport from the genus Faecalibacterium were associated with islet autoimmunity.ConclusionsThese findings demonstrate the interrelatedness of the gut microbiota, metaproteome and virome in young children. We show a functional remodeling of the gut microbiota accompanies both islet autoimmunity and viral infection with a switch in function in Faecalibacterium occurring at the onset of islet autoimmunity.E8v6si3w2ZwgkjoJioDRP1Video Abstract

【 授权许可】

CC BY   
© The Author(s) 2022

【 图 表 】

12982_2022_119_Article_IEq10.gif

Fig. 1

Fig. 5

Fig. 6

12902_2022_1242_Article_IEq1.gif

Fig. 6

13068_2022_2229_Article_IEq4.gif

Fig. 1