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Diabetes and the Microbiome

The role of the gut microbiome in the treatment, prevention, and development of diabetes

General:

Review, Jan 2019: Impact of Gut Microbiota on Host Glycemic Control https://www.frontiersin.org/articles/10.3389/fendo.2019.00029/full

Review, 2018: The Role of Gut Microbiota in Obesity and Type 2 and Type 1 Diabetes Mellitus: New Insights into “Old” Diseases http://www.mdpi.com/2076-3271/6/2/32/htm

Review, Dec 2017 Gut Microbiota Dysbiosis Drives and Implies Novel Therapeutic Strategies for Diabetes Mellitus and Related Metabolic Diseases https://www.frontiersin.org/articles/10.3389/fimmu.2017.01882/full

Review, Dec 2017 Microbial Regulation of Glucose Metabolism and Insulin Resistance: http://www.mdpi.com/2073-4425/9/1/10/htm

FMT: Washed microbiota transplantation improves patients with high blood glucose in South China (Sep 2022, n=195) https://www.frontiersin.org/articles/10.3389/fendo.2022.985636/full

Altered Gut Microbiota Activate and Expand Insulin B15-23-Reactive CD8+ T-Cells (Feb 2019) "In mice with low incidence of autoimmune diabetes, broad-spectrum antibiotic treatment led to male mice developing accelerated diabetes" http://diabetes.diabetesjournals.org/content/early/2019/02/18/db18-0487

"Fragments of bacterial cell wall released by lysozyme 1 in the intestinal lumen are necessary to regulate insulin trafficking and glucose tolerance in pancreatic beta cells". Microbiota guides insulin trafficking in beta cells (Jul 2019) https://www.nature.com/articles/s41422-019-0200-5

Intermittent administration of a fasting-mimicking diet intervenes in diabetes progression, restores β cells and reconstructs gut microbiota in mice (Nov 2018). Previous studies have shown that the gut microbiome is responsible for the benefits of fasting, & the benefits can be transferred via FMT. https://archive.fo/EsoCz#selection-1143.13-1143.14

Some viruses produce insulin-like hormones that can stimulate human cells—and have potential to cause disease https://medicalxpress.com/news/2018-02-viruses-insulin-like-hormones-human-cellsand.html

Diabetes reversal after bypass surgery linked to changes in gut microorganisms https://www.sciencedaily.com/releases/2016/07/160711092303.htm

Gut bacteria imbalance increases diabetes risk http://www.eurekalert.org/pub_releases/2016-07/uoct-gbi071216.php

Analysis of a large cohort group has found a significant connection between gut microbes and 2 of the largest risk factors for diabetes: body mass index (BMI) and lipid levels: http://www.hcplive.com/medical-news/new-study-links-bmi-lipid-levels-to-gut-microbes

Immune system uses gut bacteria to control glucose metabolism: http://oregonstate.edu/ua/ncs/archives/2016/nov/immune-system-uses-gut-bacteria-control-glucose-metabolism

Metformin & Berberine Alter Gut Microbiota Composition in Diabetes http://www.sciencedirect.com/science/article/pii/S1550413117305715 - http://www.doctorslounge.com/index.php/news/pb/68025 - http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0042529 - http://agingfree.org/Portals/0/xBlog/uploads/2017/5/24/Metformin%20alters%20the%20gut%20microbiome%20of%20individuals.pdf

Pleiotropic effects of metformin: Shaping the microbiome to manage type 2 diabetes and postpone ageing (2018): https://www.sciencedirect.com/science/article/pii/S1568163718301855

Anti-diabetes drug, Acarbose, works via gut microbiome. Nonmicrobicidal Small Molecule Inhibition of Polysaccharide Metabolism in Human Gut Microbes: A Potential Therapeutic Avenue (2018): https://pubs.acs.org/doi/10.1021/acschembio.8b00309

The gut microbiota plays key role in diabetes treatment: https://www.drugtargetreview.com/news/23589/gut-microbiota-medication/ - https://newsroom.wakehealth.edu/News-Releases/2018/12/Gut-Microbiome-May-Affect-Some-Anti-Diabetes-Drugs

Researchers find bacterial protein that boosts insulin-producing cells in zebrafish: https://www.sciencedaily.com/releases/2016/12/161213130607.htm

Recombinant Incretin-Secreting Microbe Improves Metabolic Dysfunction in High-Fat Diet Fed Rodents (2017): https://www.nature.com/articles/s41598-017-14010-x

Taking synbiotic supplements for 6 weeks among patients with gestational diabetes mellitus had beneficial effects on markers of insulin metabolism, TAG and VLDL-cholesterol concentrations. (2016) https://doi.org/10.1017/S0007114516003457

Probiotic and synbiotic supplementation could improve metabolic syndrome in prediabetic adults: A randomized controlled trial (2018): https://www.sciencedirect.com/science/article/abs/pii/S1871402118302832 "treatment decreased metabolic syndrome prevalence by 17% and 23% respectively"

Gut Microbiota-Stimulated Innate Lymphoid Cells Support β-Defensin 14 Expression in Pancreatic Endocrine Cells, Preventing Autoimmune Diabetes (2018, mice): https://www.cell.com/cell-metabolism/pdfExtended/S1550-4131(18)30394-2

Long term but not short term exposure to obesity related microbiota promotes host insulin resistance (2018): https://www.nature.com/articles/s41467-018-07146-5

Immune Response to Gut Microbes Linked to Diabetes Risk. "the findings suggest a mechanistic connection between immune recognition of microbes and autoimmunity genetics" (Feb 2019). https://www.the-scientist.com/news-opinion/immune-response-to-gut-microbes-linked-to-diabetes-risk-65416. Association of HLA-dependent islet autoimmunity with systemic antibody responses to intestinal commensal bacteria in children http://immunology.sciencemag.org/content/4/32/eaau8125

Type 1:

Review, 2018: Gut microbiome in type 1 diabetes: A comprehensive review https://onlinelibrary.wiley.com/doi/abs/10.1002/dmrr.3043

Review, 2018: Modulation of the immune system by the gut microbiota in the development of Type 1 Diabetes https://doi.org/10.1080/21645515.2018.1514354

Review, 2017: Microbiota: Diet can protect against type 1 diabetes: http://www.ncbi.nlm.nih.gov/pubmed/28422177

Type 1 FMT:

Fecal microbiota transplantation treatment of autoimmune-mediated type 1 diabetes: A systematic review (Dec 2022) https://www.frontiersin.org/articles/10.3389/fcimb.2022.1075201/full

Fecal microbiota transplantation treatment for type 1 diabetes mellitus with malnutrition: a case report (Aug 2022) https://journals.sagepub.com/doi/10.1177/20406223221117449 "nausea and vomiting were significantly relieved. In addition, constipation, nutritional status, and blood glucose control (fasting blood glucose, HbA1c) gradually improved"

Fecal microbiota transplantation treatment of autoimmune-mediated type 1 diabetes mellitus (Aug 2022, n=2) https://www.frontiersin.org/articles/10.3389/fimmu.2022.930872/full "Our results suggest that FMT is an effective treatment for autoimmune T1DM"

Faecal microbiota transplantation halts progression of human new-onset type 1 diabetes in a randomised controlled trial (Oct 2020, n=20) https://gut.bmj.com/content/early/2020/10/25/gutjnl-2020-322630 Three autologous or allogenic (healthy donor) FMTs over a period of 4 months, 12 month follow up.

Microbiota from healthy mice alleviates cognitive decline via reshaping the gut-brain metabolic axis in diabetic mice (July 2023) https://www.sciencedirect.com/science/article/abs/pii/S0009279723003058

Washed microbiota transplantation reduces glycemic variability in unstable diabetes (Oct 2023, n=14) https://onlinelibrary.wiley.com/doi/10.1111/1753-0407.13485

Type 1 Antibiotics:

Single Course of Antibiotics Early in Life May Increase Type 1 Diabetes Risk (2018): https://www.genengnews.com/gen-news-highlights/single-course-of-antibiotics-early-in-life-may-increase-type-1-diabetes-risk/81256065 - https://doi.org/10.7554/eLife.37816

A study from the Aalto University finds that environmental factors such as the prevalence of antibiotics are part of what makes Finns the most likely in the world to contract Type I diabetes: http://yle.fi/uutiset/osasto/news/finnish_study_connects_infants_intestinal_microbes_to_childhood_diabetes/9530493

Antibiotic-mediated gut microbiome perturbation accelerates development of type 1 diabetes in mice: http://www.nature.com/articles/nmicrobiol2016140

Clostridial Butyrate Biosynthesis Enzymes Are Significantly Depleted in the Gut Microbiota of Nonobese Diabetic Mice (2018). https://msphere.asm.org/content/3/5/e00492-18 "results support a model for gut microbiota influence on T1D development involving bacterium-produced metabolites as butyrate"

Evaluation of different mucosal microbiota leads to gut microbiota-based prediction of type 1 diabetes in NOD mice (Oct 2018). https://www.nature.com/articles/s41598-018-33571-z "Our results suggest that the algorithm could potentially be used in early prediction of future T1D development."

Study shows gut microbe composition different in young children with and without type 1 diabetes http://medicalxpress.com/news/2014-06-gut-microbe-composition-young-children.html

Yale study shows that gut microbes could trigger type 1 diabetes: http://www.diabetes.co.uk/news/2016/sep/yale-study-shows-that-gut-microbes-could-trigger-type-1-diabetes-99484927.html

Italian 2017 study ties inflammation, gut bacteria to type 1 diabetes: http://www.upi.com/Health_News/2017/01/19/Study-ties-inflammation-gut-bacteria-to-type-1-diabetes/3631484859891/

Multi-omic characteristics of the gut microbiome in individuals with T1DM compared to healthy relatives show a greater influence of microbes rather than genetics of T1DM. This study identifies the expression of T1DM-associated microbial functions to distinct taxa: http://www.gutmicrobiotaforhealth.com/en/integrated-multi-omics-study-human-gut-microbiome-four-families-multiple-cases-type-1-diabetes/

Gut bacteria can alter the protective effects of a gene that wards off type 1 diabetes: https://www.sciencedaily.com/releases/2017/08/170830155511.htm - Protective major histocompatibility complex allele prevents type 1 diabetes by shaping the intestinal microbiota early in ontogeny http://dx.doi.org/10.1073/pnas.1712280114

Type 1 diabetes risk linked to intestinal viruses. One virus may protect against disease, others may increase risk: https://medicine.wustl.edu/news/diabetes-risk-linked-to-intestinal-viruses/ - http://www.pnas.org/content/114/30/E6166.abstract

Innate Viral Receptor Signaling Determines Type 1 Diabetes Onset https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5623193/

Type 2:

Review, 2021: Reconstruction of intestinal microecology of Type 2 diabetes by fecal microbiota transplantation: Why and how https://pubmed.ncbi.nlm.nih.gov/34761734/

Review, 2018: Inflammation and Gut-Brain Axis During Type 2 Diabetes: Focus on the Crosstalk Between Intestinal Immune Cells and Enteric Nervous System https://doi.org/10.3389/fnins.2018.00725

Type 2 FMT:

Review, Nov 2023: Efficacy of fecal microbiota transplantation in type 2 diabetes mellitus: a systematic review and meta-analysis https://link.springer.com/article/10.1007/s12020-023-03606-1 "FMT treatment can reduce the levels of PBG, TG, HOMA-IR, TC, ALT, and DBP"

Prospective Study Reveals Host Microbial Determinants of Clinical Response to Fecal Microbiota Transplant Therapy in Type 2 Diabetes Patients (Mar 2022, n=37) https://www.frontiersin.org/articles/10.3389/fcimb.2022.820367/full "Out of 17 T2DM patients, 11 were found to significantly improve T2DM symptoms"

Fecal microbiota transplantation reverses insulin resistance in type 2 diabetes: A randomized, controlled, prospective study (Jan 2023, n=31) https://www.frontiersin.org/articles/10.3389/fcimb.2022.1089991/full

By destroying the mucous membrane in the small intestine and causing a new one to develop, scientists stabilized the blood sugar levels of people with type 2 diabetes. https://www.theguardian.com/society/2018/oct/24/spectacular-diabetes-treatment-could-end-daily-insulin-injections Duodenal Mucosal Resurfacing Elicits Improvement in Glycemic and Hepatic Parameters in Type 2 Diabetes—One-Year Multicenter Study Results (2018): http://diabetes.diabetesjournals.org/content/67/Supplement_1/1137-P

Microbially Produced Imidazole Propionate Impairs Insulin Signaling through mTORC1 (Oct 2018): https://doi.org/10.1016/j.cell.2018.09.055 "Our findings indicate that the microbial metabolite imidazole propionate may contribute to the pathogenesis of type 2 diabetes"

Metabolic improvement in obese patients after duodenal–jejunal exclusion is associated with intestinal microbiota composition changes (Feb 2019) https://www.nature.com/articles/s41366-019-0336-x "Improvement of obesity and type 2 diabetes after treatment may be promoted by changes in fecal microbiota composition"

Causal relationships among the gut microbiome, short-chain fatty acids and metabolic diseases (Feb 2019): https://www.nature.com/articles/s41588-019-0350-x "These data provide evidence of a causal effect of the gut microbiome on metabolic traits"

Fiber-fermenting bacteria improve health of type 2 diabetes patients (2018): https://www.sciencedaily.com/releases/2018/03/180308143047.htm

Further analysis reveals new gut microbiome markers of type 2 diabetes mellitus https://link.springer.com/article/10.1007/s10482-016-0805-3

A human gut phage catalog correlates the gut phageome with type 2 diabetes (2018): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5796561/

Researchers from the University of Eastern Finland found that an intestinal bacteria may protect against type 2 diabetes. Indolepropionic acid is a metabolite produced by intestinal bacteria, which comes from a high-fiber diet: http://www.upi.com/Health_News/2017/04/11/Study-shows-intestinal-bacteria-may-prevent-type-2-diabetes/9291491921870/

Type II diabetes may be reversible using caloric restriction: /r/AdvancedFitness/comments/4bjg5t/type_ii_diabetes_may_be_reversible_using_caloric/

Lactobacillus casei CCFM419 attenuated type 2 diabetes via gut microbiota dependent mechanism [mice]: http://pubs.rsc.org/en/content/articlelanding/2017/fo/c7fo00593h#!divAbstract - Full study via sci-hub.

Targeting gut microbiota: Lactobacillus alleviated type 2 diabetes via inhibiting LPS secretion and activating GPR43 pathway [rats]: http://www.sciencedirect.com/science/article/pii/S1756464617305492 - Full study via sci-hub.

Gut Microbiome Composition Is Predictive of Incident Type 2 Diabetes in a Population Cohort of 5,572 Finnish Adults (Jan 2022) https://diabetesjournals.org/care/article/45/4/811/141052/Gut-Microbiome-Composition-Is-Predictive-of

The association of type II diabetes with gut microbiota composition: http://www.sciencedirect.com/science/article/pii/S0882401017308045

Systematic review assessing the effectiveness of dietary intervention on gut microbiota in adults with type 2 diabetes (2018): https://link.springer.com/article/10.1007%2Fs00125-018-4632-0 "Dietary intervention was found to modulate the gut microbiota and improve glucose control in individuals with type 2 diabetes."

Diabetes-Associated Alterations in the Cecal Microbiome and Metabolome are Independent of Diet or Environment in the UC Davis Type 2-Diabetes Mellitus Rat Model (2018): https://www.physiology.org/doi/abs/10.1152/ajpendo.00203.2018