Cutting Edge: Commensal Microbiota Has Disparate Effects on Manifestations of Polyglandular Autoimmune Inflammation

Abstract

Polyglandular autoimmune inflammation accompanies Type 1 diabetes (T1D) in NOD mice affecting organs like thyroid and salivary glands. Whereas commensals are not required for T1D progression, germ-free (GF) mice had a very low degree of sialitis, which was restored by colonization with select microbial lineages. Moreover, unlike T1D, which is blocked in mice lacking MyD88-signaling adaptor under conventional but not under GF housing conditions, sialitis did not develop in MyD88-negative GF mice. Thus, microbes and MyD88-dependent signaling are critically required for sialitis development. The severity of sialitis did not correlate with the degree of insulitis in the same animal, was less sensitive to T1D-reducing diet, but was similar to T1D in microbiota-dependent sexual dimorphism. The unexpected distinction in requirements for the microbiota for different autoimmune pathologies within the same organism is crucial for understanding the nature of microbial involvement in complex autoimmune disorders including human autoimmune polyglandular syndromes.

Targeting gut microbiota and barrier function with prebiotics to alleviate autoimmune manifestations in NOD mice

“…Here, we demonstrate that the prebiotic compound XOS can change the gut microbiota and delay the onset of type 1 diabetes in NOD mice and reduce autoimmune cellular reactions against pancreatic beta cells and salivary glands. This is in line with previous results demonstrating that a variety of intestinal bacteria can regulate the degree of both insulitis and sialadenitis in NOD mice [16,28,29]. The high degree of insulitis in antibiotic-treated mice resembles that observed in germ-free NOD mice [29].…”

“…It is worth considering that in such a scenario, without XOS as an available nutrient source, the microbiota may function differently and, therefore, a microbiotamediated anti-inflammatory effect of an XOS-supplemented diet should therefore not be ruled out. In contrast to the effect on insulitis, the development of sialadenitis was clearly regulated by gut bacteria, which is comparable with our previous study in germ-free mice [16]. These findings warrant further investigation into the regulatory role of Parabacteroides spp.…”

“…Histology Insulitis and sialadenitis were scored in a blinded fashion on at least 50 islets per pancreas and in 8 sequential sections of each salivary gland from 13-week-old mice on H&E-stained 5 μm sections with 40 μm intervals; they were graded as previously described [16].…”

Salivary‐gland‐protective regulatory T‐cell dysfunction underlies female‐specific sialadenitis in the non‐obese diabetic mouse model of Sjögren syndrome

“…Previous studies in NOD mice had shown that altering female sex hormones through castration did not modulate the development of sialadenitis in females, whereas castration of males increased development of sialadenitis (Fig. c) . Similar proportions of Treg cells were observed in castrated and sham‐castrated mice, indicating that this effect was not the result of differences in the frequency of Treg cells in the absence of testosterone (Fig.…”

Таксономічний Склад І Популяційний Рівень Мікробіому Вмісту Порожнини Товстої Кишки Білих Щурів З Експериментальним Тиреотоксикозом

“…Дисбактеріоз/дисбіоз, сформу-вавшись як супутній стан, може призвести до низ-ки ускладнень, що негативно впливають на перебіг основного захворювання. Саме дисбактеріоз може ставати провідним захворюванням -інфекційним процесом змішаної етіології [19].…”