Comment on: Brugman S et al. (2006) Antibiotic treatment partially protects against type 1 diabetes in the Bio-Breeding diabetes-prone rat. Is the gut flora involved in the development of type 1 diabetes? Diabetologia 49:2105–2108

Schwartz, R. Fletcher; Neu, Josef; Schatz, Desmond; Atkinson, Mark A.; Wasserfall, Clive

doi:10.1007/s00125-006-0526-7

Cited by 48 publications

(38 citation statements)

References 8 publications

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“…Furthermore, diabetes-prone BB rats (BBDP) subject to Cesarean derivation have been noted to develop accelerated disease (7). In terms of using such information to proactively modulate diabetes formation, the provision of antibiotics, such as fucidic acid, Colistin, and Bactrim, in BB rats after weaning (8,9) lead to diabetes prevention, whereas in our own efforts using the NOD mouse, a decreased frequency of type 1 diabetes was observed with the administration of doxycycline (10). The specific mechanisms of how such therapies modulate disease are unclear, but it is clear that changes in the microbiota affect the development of autoimmune diabetes in both animal models.…”

Section: Altered Intestinal Microbiotamentioning

confidence: 85%

The “Perfect Storm” for Type 1 Diabetes

2008

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It is often stated that type 1 diabetes results from a complex interplay between varying degrees of genetic susceptibility and environmental factors. While agreeing with this principal, our desire is that this Perspectives article will highlight another complex interplay potentially associated with this disease involving facets related to the gut, one where individual factors that, upon their interaction with each another, form a "perfect storm" critical to the development of type 1 diabetes. This trio of factors includes an aberrant intestinal microbiota, a "leaky" intestinal mucosal barrier, and altered intestinal immune responsiveness. Studies examining the microecology of the gastrointestinal tract have identified specific microorganisms whose presence appears related (either quantitatively or qualitatively) to disease; in type 1 diabetes, a role for microflora in the pathogenesis of disease has recently been suggested. Increased intestinal permeability has also been observed in animal models of type 1 diabetes as well as in humans with or at increased-risk for the disease. Finally, an altered mucosal immune system has been associated with the disease and is likely a major contributor to the failure to form tolerance, resulting in the autoimmunity that underlies type 1 diabetes. Herein, we discuss the complex interplay between these factors and raise testable hypotheses that form a fertile area for future investigations as to the role of the gut in the pathogenesis and prevention of type 1 diabetes.

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Section: Altered Intestinal Microbiotamentioning

confidence: 85%

The “Perfect Storm” for Type 1 Diabetes

2008

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“…The protective role of antibiotic doxycycline was also found in NOD-mice. These results suggest that microbial composition is of importance in development of type 1 diabetes in genetically susceptible rodents (30,65). In addition, in obese mice, the administration of norfloxacin and ampicilline ameliorates glucose tolerance and reduces hepatic steatosis.…”

Section: Attenuation Of the Intestinal Barriermentioning

confidence: 87%

Leaky gut and diabetes mellitus: what is the link?

2011

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Diabetes mellitus is a chronic disease requiring lifelong medical attention. With hundreds of millions suffering worldwide, and a rapidly rising incidence, diabetes mellitus poses a great burden on healthcare systems. Recent studies investigating the underlying mechanisms involved in disease development in diabetes point to the role of the dys-regulation of the intestinal barrier. Via alterations in the intestinal permeability, intestinal barrier function becomes compromised whereby access of infectious agents and dietary antigens to mucosal immune elements is facilitated, which may eventually lead to immune reactions with damage to pancreatic beta cells and can lead to increased cytokine production with consequent insulin resistance. Understanding the factors regulating the intestinal barrier function will provide important insight into the interactions between luminal antigens and immune response elements. This review analyses recent advances in the mechanistic understanding of the role of the intestinal epithelial barrier function in the development of type 1 and type 2 diabetes. Given our current knowledge, we may assume that reinforcing the intestinal barrier can offer and open new therapeutic horizons in the treatment of type 1 and type 2 diabetes.

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“…Direct evidence exists in rodents, as diabetes is aggravated under specific pathogen-free conditions or upon administration of antibiotics (27). In other studies, however, administration of antibiotics prevents diabetes (68,384). Perhaps autoimmunity ensues whenever the intricate microbial balance in the intestine is disturbed.…”

Section: B Bacteriamentioning

confidence: 99%

Type 1 Diabetes: Etiology, Immunology, and Therapeutic Strategies

Belle

Coppieters

Herrath

2011

Physiological Reviews

844

695

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Type 1 diabetes (T1D) is a chronic autoimmune disease in which destruction or damaging of the beta-cells in the islets of Langerhans results in insulin deficiency and hyperglycemia. We only know for sure that autoimmunity is the predominant effector mechanism of T1D, but may not be its primary cause. T1D precipitates in genetically susceptible individuals, very likely as a result of an environmental trigger. Current genetic data point towards the following genes as susceptibility genes: HLA, insulin, PTPN22, IL2Ra, and CTLA4. Epidemiological and other studies suggest a triggering role for enteroviruses, while other microorganisms might provide protection. Efficacious prevention of T1D will require detection of the earliest events in the process. So far, autoantibodies are most widely used as serum biomarker, but T-cell readouts and metabolome studies might strengthen and bring forward diagnosis. Current preventive clinical trials mostly focus on environmental triggers. Therapeutic trials test the efficacy of antigen-specific and antigen-nonspecific immune interventions, but also include restoration of the affected beta-cell mass by islet transplantation, neogenesis and regeneration, and combinations thereof. In this comprehensive review, we explain the genetic, environmental, and immunological data underlying the prevention and intervention strategies to constrain T1D.

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Comment on: Brugman S et al. (2006) Antibiotic treatment partially protects against type 1 diabetes in the Bio-Breeding diabetes-prone rat. Is the gut flora involved in the development of type 1 diabetes? Diabetologia 49:2105–2108

Cited by 48 publications

References 8 publications

The “Perfect Storm” for Type 1 Diabetes

The “Perfect Storm” for Type 1 Diabetes

Leaky gut and diabetes mellitus: what is the link?

Type 1 Diabetes: Etiology, Immunology, and Therapeutic Strategies

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