Gut immune deficits in LEW.1AR1‐<i>iddm</i> rats partially overcome by feeding a diabetes‐protective diet

Crookshank, Jennifer A.; Patrick, Christopher; Wang, Gensheng; Noel, Janet; Scott, Fraser W.

doi:10.1111/imm.12457

Cited by 7 publications

(4 citation statements)

References 61 publications

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“…CRAMP’s essential role in maintaining gut microbiota homeostasis may have contributed to the reduced diabetes incidence ( 175 ). Similar results were obtained in the diabetes-prone LEW.1AR1-iddm rat model when fed either the cereal or HC diet, with the HC diet group exhibiting significantly reduced diabetes and Ifng to Il4 mRNA when compared to the cereal group ( 176 ).…”

Section: Environmental Factors and T Cell Phenotype In T1dsupporting

confidence: 76%

Host-microbiota interactions shaping T-cell response and tolerance in type 1 diabetes

2022

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Type-1 Diabetes (T1D) is a complex polygenic autoimmune disorder involving T-cell driven beta-cell destruction leading to hyperglycemia. There is no cure for T1D and patients rely on exogenous insulin administration for disease management. T1D is associated with specific disease susceptible alleles. However, the predisposition to disease development is not solely predicted by them. This is best exemplified by the observation that a monozygotic twin has just a 35% chance of developing T1D after their twin’s diagnosis. This makes a strong case for environmental triggers playing an important role in T1D incidence. Multiple studies indicate that commensal gut microbiota and environmental factors that alter their composition might exacerbate or protect against T1D onset. In this review, we discuss recent literature highlighting microbial species associated with T1D. We explore mechanistic studies which propose how some of these microbial species can modulate adaptive immune responses in T1D, with an emphasis on T-cell responses. We cover topics ranging from gut-thymus and gut-pancreas communication, microbial regulation of peripheral tolerance, to molecular mimicry of islet antigens by microbial peptides. In light of the accumulating evidence on commensal influences in neonatal thymocyte development, we also speculate on the link between molecular mimicry and thymic selection in the context of T1D pathogenesis. Finally, we explore how these observations could inform future therapeutic approaches in this disease.

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Section: Environmental Factors and T Cell Phenotype In T1dsupporting

confidence: 76%

Host-microbiota interactions shaping T-cell response and tolerance in type 1 diabetes

2022

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“…HCD has anti-inflammatory and anti-diabetogenic effects in rodent models of T1D, including the BB rat [ 22 , 41 – 43 ]. Further, antibiotic treatment also protects lymphopenic BB rats from diabetes progression [ 19 , 44 ].…”

Section: Resultsmentioning

confidence: 99%

Modulation of the diet and gastrointestinal microbiota normalizes systemic inflammation and β-cell chemokine expression associated with autoimmune diabetes susceptibility

et al. 2018

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Environmental changes associated with modern lifestyles may underlie the rising incidence of Type 1 diabetes (T1D). Our previous studies of T1D families and the BioBreeding (BB) rat model have identified a peripheral inflammatory state that is associated with diabetes susceptibility, consistent with pattern recognition receptor ligation, but is independent of disease progression. Here, compared to control strains, islets of spontaneously diabetic BB DRlyp/lyp and diabetes inducible BB DR+/+ weanlings provided a standard cereal diet expressed a robust proinflammatory transcriptional program consistent with microbial antigen exposure that included numerous cytokines/chemokines. The dependence of this phenotype on diet and gastrointestinal microbiota was investigated by transitioning DR+/+ weanlings to a gluten-free hydrolyzed casein diet (HCD) or treating them with antibiotics to alter/reduce pattern recognition receptor ligand exposure. Bacterial 16S rRNA gene sequencing revealed that these treatments altered the ileal and cecal microbiota, increasing the Firmicutes:Bacteriodetes ratio and the relative abundances of lactobacilli and butyrate producing taxa. While these conditions did not normalize the inherent hyper-responsiveness of DR+/+ rat leukocytes to ex vivo TLR stimulation, they normalized plasma cytokine levels, plasma TLR4 activity levels, the proinflammatory islet transcriptome, and β-cell chemokine expression. In lymphopenic DRlyp/lyp rats, HCD reduced T1D incidence, and the introduction of gluten to this diet induced islet chemokine expression and abrogated protection from diabetes. Overall, these studies link BB rat islet-level immunocyte recruiting potential, as measured by β-cell chemokine expression, to a genetically controlled immune hyper-responsiveness and innate inflammatory state that can be modulated by diet and the intestinal microbiota.

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“…In the last 5 years an increasing number of studies using animal models have shown that the intake of dietary fibers plays an important role in maintaining gut microbiota homeostasis; this leads to a delay in the development of T1D ( Table 5 ). For example, feeding LEW.1AR1-iddm rats with a low antigen, hydrolyzed casein-based diet was shown to correct gut immune cell deficits and increase immunoregulatory capacity leading to protection against T1D ( 150 ). Similarly, feeding NOD mice with wheat flour for 72 days shows the same effect with a decrease in the levels of IFN-γ (a proinflammatory cytokine involved in the autoimmune pathogenesis of T1D) and an increase in the levels of IL-10 (an anti-inflammatory cytokine potentially implicated in hindering T1D development) ( 127 ).…”

Section: Future Of T1d Management By Microbiome Therapymentioning

confidence: 99%

Epigenetic Effects of Gut Metabolites: Exploring the Path of Dietary Prevention of Type 1 Diabetes

et al. 2020

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Type 1 diabetes (T1D) has increased over the past half century and has now become the second most frequent autoimmune disease in childhood and one of major public health concern worldwide. Evidence suggests that modern lifestyles and rapid environmental changes are driving factors that underlie this increase. The integration of these two factors brings about changes in food intake. This, in turn, alters epigenetic regulations of the genome and intestinal microbiota composition, which may ultimately play a role in pathogenesis of T1D. Recent evidence shows that dysbiosis of the gut microbiota is closely associated with T1D and that a dietary intervention can influence epigenetic changes associated with this disease and may modify gene expression patterns through epigenetic mechanisms. In this review focus on how a diet can shape the gut microbiome, its effect on the epigenome in T1D, and the future of T1D management by microbiome therapy.

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Gut immune deficits in LEW.1AR1‐iddm rats partially overcome by feeding a diabetes‐protective diet

Cited by 7 publications

References 61 publications

Host-microbiota interactions shaping T-cell response and tolerance in type 1 diabetes

Host-microbiota interactions shaping T-cell response and tolerance in type 1 diabetes

Modulation of the diet and gastrointestinal microbiota normalizes systemic inflammation and β-cell chemokine expression associated with autoimmune diabetes susceptibility

Epigenetic Effects of Gut Metabolites: Exploring the Path of Dietary Prevention of Type 1 Diabetes

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