The Impact of Intestinal Microorganisms and Their Metabolites on Type 1 Diabetes Mellitus

Abstract

Background

Type 1 diabetes mellitus (T1DM) is an autoimmune disease with a complex etiology comprising numerous genetic and environmental factors; however, many of the mechanisms underlying disease development remain unclear. Nevertheless, a critical role has recently been assigned to intestinal microorganisms in T1DM disease pathogenesis. In particular, a decrease in intestinal microbial diversity, increase in intestinal permeability, and the translocation of intestinal bacteria to the pancreas have been reported in patients and animal models with T1DM. Moreover, intestinal microbial metabolites differ between healthy individuals and patients with T1DM. Specifically, short-chain fatty acid (SCFA) production, which contributes to intestinal barrier integrity and immune response regulation, is significantly reduced in patients with T1DM. Considering this correlation between intestinal microorganisms and T1DM, many studies have investigated the potential of intestinal microbiota in preventive and therapeutic strategies for T1DM.

Objective

The aim of this review is to provide further support for the notion that intestinal microbiota contributes to the regulation of T1DM occurrence and development. In particular, this article reviews the involvement of the intestinal microbiota and the associated metabolites in T1DM pathogenesis, as well as recent studies on the involvement of the intestinal microbiota in T1DM prevention and treatment.

Conclusion

Intestinal microbes and their metabolites contribute to T1DM occurrence and development and may become a potential target for novel therapeutics.

Keywords:

• type 1 diabetes mellitus
• intestinal microorganisms
• intestinal microbiota
• dysbiosis
• metabolites
• prevention and treatment

Abbreviations

APC, antigen-presenting cell; AhR, aryl hydrocarbon receptor; ADSCs, adipose-derived stem cells; CRAMP, cathelicidin-associated antimicrobial peptide; CPT1A, carnitine palmitoyltransferase 1A; CTRs, controls; DC, dendritic cell; DSS, dextran sulfate sodium; GF, germ-free; HDAC, histone deacetylase; HIF1α, hypoxia-inducible factor 1α; HP, Heligmosomoides polygyrus; KRV, Kilham rat virus; I–IFN, type I interferon; LMP, low-methoxyl pectin; LPS, lipopolysaccharides; NOD, non-obese diabetes mellitus; NOD BDC2.5 TCR-Tg, non-obese diabetic (NOD) BDC2.5 TCR-transgenic (Tg); PLN, pancreatic lymph nodes; PSA, polysaccharide; P1Ab, individuals who tested positive for at least one antibody but did not progress to clinical T1DM; PT1D, progressors to T1DM; SCFAs, short-chain fatty acids; SFB, segmented filamentous bacteria; STZ, streptozotocin; T1DM, type 1 diabetes mellitus; YBG, yeast β-glucan.

Acknowledgments

The authors thank Editage for English editing and proofreading.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.

Additional information

Funding

The authors are grateful to financial support from National Natural Science Foundation of China, PR China (No. 81460156), Science and Technology Innovation Leading Academics of National High-level Personnel of Special Support Program, PR China (No. GKFZ-2018-29), Guizhou High-Level Innovative Talent Support Program, PR China (No. QKH-RC-2022-0001), the Science and Technology Foundation of Guizhou, PR China (No. QKHQKHJC-ZK-2021-ZD-026), and S&T Foundation of Zunyi Science and Technology Bureau, PR China (No. ZSK-RC-2020-1).