Distinct alterations of gut morphology and microbiota characterize accelerated diabetes onset in nonobese diabetic mice

Simon, Marie‐Christine; Reinbeck, Anna Lena; Wessel, C; Heindirk, Julia; Kaul, Kirti; Arreguín-Cano, Juan Antonio; Strom, Alexander; Blaut, Michaël; Bäckhed, Fredrik; Burkart, Volker; Roden, Michael

doi:10.1016/s0021-9258(17)49908-x

Cited by 23 publications

(14 citation statements)

References 55 publications

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“…The molecular mechanism and signaling pathways of this process have many similarities to those of traditional inflammatory reactions, and this phenomenon is different from a slow inflammatory response [ 23 , 24 ]. In recent years, studies have shown that immune receptor-mediated signaling pathways also play an important role in metabolic inflammation in diabetes [ 25 ]. The NOD-like receptors (NLRs) belong to the class of intracellular sensor molecules [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Role of NOD-Like Receptors in a Miniature Pig Model of Diabetic Renal Injuries

Ren

Cui

Hong

et al. 2022

Mediators of Inflammation

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Activation of NOD-like receptor (NLR) signaling pathway can promote downstream cytokine and proinflammatory cytokines release, and inflammation induced by excess nutrients leads to renal metabolic injury. How the NLRs influence metabolic progress and then lead to the renal injury remains poorly investigated. Compared with rodents, minipigs are more similar to humans and are more ideal animal models for human disease research. In this study, we established a diabetic minipig model through a high-sugar and high-fat diet combined with streptozotocin (STZ) injection. Blood biological markers and renal pathological markers, expression of NLRP subfamily members (NLRP1 and NLRP3) and their downstream cytokines (precursors of IL-1β and IL-18 and mature forms of IL-1β and IL-18), expression of NLRC subfamily members (NLRC1, NLRC2, and NLRC5) and their downstream nuclear factor-κB (NF-κB) signaling pathway molecules (IKKβ, IκBα, and NF-κB p65), and inflammatory cytokines (TNF-α and interleukin-6 (IL-6)) were systematically evaluated. The expression of NLRP3 and its downstream cytokine signaling molecules, the precursors of IL-1β and IL-18, and the mature forms of IL-1β and IL-18 was significantly upregulated. The expression levels of NLRC1, NLRC2, and NLRC5 and activation of the downstream NF-κB pathway molecules phospho-IKKβ, phospho-IκBα, NF-κB p65, and phospho-NF-κB p65 were significantly increased. The TNF-α and IL-6 levels were significantly increased in diabetic pig kidneys. The TGF-β/Smad signaling molecules, TGF-β and P-SMAD2/3, were also increased. These results suggested that the metabolic inflammation activated by NLRs might play an important role in diabetic renal injuries.

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Section: Discussionmentioning

confidence: 99%

Role of NOD-Like Receptors in a Miniature Pig Model of Diabetic Renal Injuries

Ren

Cui

Hong

et al. 2022

Mediators of Inflammation

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“…antigens. Microbiota can regulate T1D through TLR signaling differences (61,62). For instance, imbalance between TLR2 vs. TLR4 stimulation can determine T1D susceptibility where TLR2 provides a pro-diabetic signal whereas TLR4 provides microbiota-induced tolerization (61).…”

Section: The Microbiome and T1dmentioning

confidence: 99%

Virus Infection Is an Instigator of Intestinal Dysbiosis Leading to Type 1 Diabetes

Morse

Horwitz

2021

Front. Immunol.

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In addition to genetic predisposition, environmental determinants contribute to a complex etiology leading to onset of type 1 diabetes (T1D). Multiple studies have established the gut as an important site for immune modulation that can directly impact development of autoreactive cell populations against pancreatic self-antigens. Significant efforts have been made to unravel how changes in the microbiome function as a contributor to autoimmune responses and can serve as a biomarker for diabetes development. Large-scale longitudinal studies reveal that common environmental exposures precede diabetes pathology. Virus infections, particularly those associated with the gut, have been prominently identified as risk factors for T1D development. Evidence suggests recent-onset T1D patients experience pre-existing subclinical enteropathy and dysbiosis leading up to development of diabetes. The start of these dysbiotic events coincide with detection of virus infections. Thus viral infection may be a contributing driver for microbiome dysbiosis and disruption of intestinal homeostasis prior to T1D onset. Ultimately, understanding the cross-talk between viral infection, the microbiome, and the immune system is key for the development of preventative measures against T1D.

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“…Then, to emphasize the importance of gut microbiota in inflammatory conditions, three original research articles explored this subject in animal models (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28). Watanabe et al evaluated the importance of these microorganisms in chronic kidney disease (CKD), by treating C57BL/6 mice, which were submitted to unilateral ureteral obstruction (UUO), with broad-spectrum antibiotics.…”

Section: Editorial On Research Topic Intestinal Dysbiosis In Inflammatory Diseasesmentioning

confidence: 99%