Alterations in Intestinal Microbiota Correlate With Susceptibility to Type 1 Diabetes

Abstract

We tested the hypothesis that alterations in the intestinal microbiota are linked with the progression of type 1 diabetes (T1D). Herein, we present results from a study performed in subjects with islet autoimmunity living in the U.S. High-throughput sequencing of bacterial 16S rRNA genes and adjustment for sex, age, autoantibody presence, and HLA indicated that the gut microbiomes of seropositive subjects differed from those of autoantibody-free first-degree relatives (FDRs) in the abundance of four taxa. Furthermore, subjects with autoantibodies, seronegative FDRs, and new-onset patients had different levels of the Firmicutes genera Lactobacillus and Staphylococcus compared with healthy control subjects with no family history of autoimmunity. Further analysis revealed trends toward increased and reduced abundances of the Bacteroidetes genera Bacteroides and Prevotella, respectively, in seropositive subjects with multiple versus one autoantibody. Canonical discriminant analysis suggested that the gut microbiomes of autoantibody-positive individuals and seronegative FDRs clustered together but separate from those of new-onset patients and unrelated healthy control subjects. Finally, no differences in biodiversity were evident in seropositive versus seronegative FDRs. These observations suggest that altered intestinal microbiota may be associated with disease susceptibility.

Type 1 Diabetes and Intestinal Microbiota: How Geographic Differences Between Human Cohorts Can Influence Interpretation of Associations

“…In the BABYDIET cohort study in Germany, subjects with a high abundance of Bacteroides at 6 months of age were at an increased risk of early autoantibody development, but this trend was not particularly prevalent in subjects included in the study [24]. Similar differences were not seen in a longitudinal case-control comparison in DIABIMMUNE, a study of Finnish and Estonian children [25], or in a cross-sectional study conducted in Denver, Colorado [26], possibly due to differences in study protocol, sample size, and geographic location (Table 1). Specifically, Finnish children enrolled in the DIABIMMUNE study were from Espoo, Finland whereas those with increased B. dorei enrolled in DIPP were from Turku, Finland.…”

“…The microbial diversity of pre-autoimmune children is not well defined, with some studies reporting clear decreases in diversity prior to seroconversion [22,23] while other studies see no difference in diversity measures between those that seroconvert and healthy controls [25,26,30]. Meanwhile, a decrease in microbial diversity after seroconversion but prior to T1D onset was reported [25].…”

“…So far, studies limited to one clinical site tend to report taxonomic differences between cases and controls [21,22,26,29], while studies with subjects from multiple geographically distinct sites do not report such associations [30]. The BABYDIET study, which enrolled children with a first-degree relative with T1D, did not see any taxonomic or functional differences in children prior to seroconversion [30].…”

Стан Мікробіоти Порожнини Товстого Кишечника У хворих На цукровий Діабет 1-Го Типу Залежно Від Тяжкості Клінічного Перебігу

“…Негативні емоції на больовий синдром особливо небезпечні за на-явності супутніх захворювань, зокрема ЦД 1-го типу [15]. При цьому порушуються практично всі види обмі-ну речовин, характерним є ураження більшості органів і систем організму, що в подальшому призводить до ви-никнення тяжких ускладнень і високої летальності хво-рих [12][13][14]. Порушення регенераторної функції тка-нин, послаблення фагоцитарної активності макрофагів і лейкоцитів та зниження захисного бар'єру слизових оболонок сприяють посиленню адгезії мікроорганізмів та формуванню хронічних вогнищ інфекції, зокрема в піднебінних мигдаликах і приносових пазухах [11].…”

Understanding Luminal Microorganisms and Their Potential Effectiveness in Treating Intestinal Inflammation

“…Some studies have found an association between antibiotic use during infancy or early childhood and the development of inflammatory bowel disease (IBD), suggesting that environmental factors, altering microbiota – especially in early childhood - may trigger inflammation(14, 15). Shifting the microbiota composition may induce autoimmune reactivity(16, 17). …”