Auto-immunity and the gut microbiome in type 1 diabetes: Lessons from rodent and human studies

Snethlage, Coco M. Fuhri; Nieuwdorp, Max; Raalte, Daniël H. van; Rampanelli, Elena; Verchere, Bruce; Hanssen, Nordin M.J.

doi:10.1016/j.beem.2021.101544

Cited by 16 publications

(10 citation statements)

References 84 publications

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“…The gut microbiome is, in addition to its symbiotic functions by regulating the inflammatory and immunological tone of the host [20] and prevention of pathogenic overgrowth of harmful microbes such as Clostridium difficile, increasingly compared to an endocrine organ [21]. Herein, the gut microbiome produces a range of metabolites that interact with specific receptors, altering the phenotype of the host.…”

Section: Introductionmentioning

confidence: 99%

Interactions between Tryptophan Metabolism, the Gut Microbiome and the Immune System as Potential Drivers of Non-Alcoholic Fatty Liver Disease (NAFLD) and Metabolic Diseases

2022

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The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing and therefore is its burden of disease as NALFD is a risk factor for cirrhosis and is associated with other metabolic conditions such as type II diabetes, obesity, dyslipidaemia and atherosclerosis. Linking these cardiometabolic diseases is a state of low-grade inflammation, with higher cytokines and c-reactive protein levels found in individuals with NAFLD, obesity and type II diabetes. A possible therapeutic target to decrease this state of low-grade inflammation is the metabolism of the essential amino-acid tryptophan. Its three main metabolic pathways (kynurenine pathway, indole pathway and serotonin/melatonin pathway) result in metabolites such as kynurenic acid, xanturenic acid, indole-3-propionic acid and serotonin/melatonin. The kynurenine pathway is regulated by indoleamine 2,3-dioxygenase (IDO), an enzyme that is upregulated by pro-inflammatory molecules such as INF, IL-6 and LPS. Higher activity of IDO is associated with increased inflammation and fibrosis in NAFLD, as well with increased glucose levels, obesity and atherosclerosis. On the other hand, increased concentrations of the indole pathway metabolites, regulated by the gut microbiome, seem to result in more favorable outcomes. This narrative review summarizes the interactions between tryptophan metabolism, the gut microbiome and the immune system as potential drivers of cardiometabolic diseases in NAFLD.

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Section: Introductionmentioning

confidence: 99%

Interactions between Tryptophan Metabolism, the Gut Microbiome and the Immune System as Potential Drivers of Non-Alcoholic Fatty Liver Disease (NAFLD) and Metabolic Diseases

2022

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“…Preclinical and clinical T1D is mostly associated with GIT pathogenesis, such as celiac disease or increased intestinal leakage potentially due to microbial dysbiosis ( 41 – 43 ). Multiple studies report significant shifts in gut microbes including bacteria, viruses, and fungi before the onset of T1D as reviewed ( 44 ). Figure 2 illustrates the balanced microbial interaction that contributes to glucose metabolism and suppresses hyperglycemia.…”

Section: Microbial Dysbiosis Drives Systemic Autoimmune Diseasesmentioning

confidence: 99%

Microbial dysbiosis in the gut drives systemic autoimmune diseases

Mousa

Chehadeh²,

Husband³

2022

Front. Immunol.

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Trillions of microbes survive and thrive inside the human body. These tiny creatures are crucial to the development and maturation of our immune system and to maintain gut immune homeostasis. Microbial dysbiosis is the main driver of local inflammatory and autoimmune diseases such as colitis and inflammatory bowel diseases. Dysbiosis in the gut can also drive systemic autoimmune diseases such as type 1 diabetes, rheumatic arthritis, and multiple sclerosis. Gut microbes directly interact with the immune system by multiple mechanisms including modulation of the host microRNAs affecting gene expression at the post-transcriptional level or production of microbial metabolites that interact with cellular receptors such as TLRs and GPCRs. This interaction modulates crucial immune functions such as differentiation of lymphocytes, production of interleukins, or controlling the leakage of inflammatory molecules from the gut to the systemic circulation. In this review, we compile and analyze data to gain insights into the underpinning mechanisms mediating systemic autoimmune diseases. Understanding how gut microbes can trigger or protect from systemic autoimmune diseases is crucial to (1) tackle these diseases through diet or lifestyle modification, (2) develop new microbiome-based therapeutics such as prebiotics or probiotics, (3) identify diagnostic biomarkers to predict disease risk, and (4) observe and intervene with microbial population change with the flare-up of autoimmune responses. Considering the microbiome signature as a crucial player in systemic autoimmune diseases might hold a promise to turn these untreatable diseases into manageable or preventable ones.

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“…Bacteria and their products are vital contributors to impairment and permeability of the gut barrier, resulting in an increased influx of bacteria, endotoxin, bacterial DNA, and metabolites into the host circulation. Recent reviews show that microbial dysbiosis and impaired barrier function are associated with gastrointestinal disease [113][114][115], neurodegenerative disease [116][117][118][119], autoimmune disease [120][121][122][123][124][125], and an impaired metabolic status in the host manifested by obesity, insulin resistance and cardiovascular complications [126][127][128][129][130][131][132][133][134][135]. In several animal models [63,64,107,136,137], exposure to PQQ increases mRNA expression levels of tight junction proteins and improves jejunal barrier function, suggesting PQQ may act through the gut to affect tissues in the periphery.…”

Section: Intestinal Barrier Functions and The Microbiomementioning

confidence: 99%

Pyrroloquinoline-Quinone Is More Than an Antioxidant: A Vitamin-like Accessory Factor Important in Health and Disease Prevention

2021

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Pyrroloquinoline quinone (PQQ) is associated with biological processes such as mitochondriogenesis, reproduction, growth, and aging. In addition, PQQ attenuates clinically relevant dysfunctions (e.g., those associated with ischemia, inflammation and lipotoxicity). PQQ is novel among biofactors that are not currently accepted as vitamins or conditional vitamins. For example, the absence of PQQ in diets produces a response like a vitamin–related deficiency with recovery upon PQQ repletion in a dose-dependent manner. Moreover, potential health benefits, such as improved metabolic flexibility and immuno-and neuroprotection, are associated with PQQ supplementation. Here, we address PQQ’s role as an enzymatic cofactor or accessory factor and highlight mechanisms underlying PQQ’s actions. We review both large scale and targeted datasets demonstrating that a neonatal or perinatal PQQ deficiency reduces mitochondria content and mitochondrial-related gene expression. Data are reviewed that suggest PQQ’s modulation of lactate acid and perhaps other dehydrogenases enhance NAD+–dependent sirtuin activity, along with the sirtuin targets, such as PGC-1α, NRF-1, NRF-2 and TFAM; thus, mediating mitochondrial functions. Taken together, current observations suggest vitamin-like PQQ has strong potential as a potent therapeutic nutraceutical.

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Auto-immunity and the gut microbiome in type 1 diabetes: Lessons from rodent and human studies

Cited by 16 publications

References 84 publications

Interactions between Tryptophan Metabolism, the Gut Microbiome and the Immune System as Potential Drivers of Non-Alcoholic Fatty Liver Disease (NAFLD) and Metabolic Diseases

Interactions between Tryptophan Metabolism, the Gut Microbiome and the Immune System as Potential Drivers of Non-Alcoholic Fatty Liver Disease (NAFLD) and Metabolic Diseases

Microbial dysbiosis in the gut drives systemic autoimmune diseases

Pyrroloquinoline-Quinone Is More Than an Antioxidant: A Vitamin-like Accessory Factor Important in Health and Disease Prevention

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