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supportedtopmoderate inflation risk

Intestinal permeability

type 2 diabetes

Intestinal permeability looks like a credible signal in type 2 diabetes, though some caution is still warranted.

Intestinal permeability shows a moderate evidence base in type 2 diabetes, with multiple central papers and additional supporting literature.

intestinal_permeability
Credibility score
97
Human translation
3/5
Reproducibility
5/5
Novelty
1/5
Actionability
3/5
Credibility 97Human translation 3/5Reproducibility 5/5Novelty 1/5Actionability 3/5
Why this scores the way it does
  • moderate central evidence base
  • meaningful supporting human literature
  • dense review literature
Main caveats
  • directionality and confounding still require curated review

Internal review flags

2 flags
preclinical_heavy

Preclinical evidence exceeds central human evidence. Interpret translational relevance cautiously.

review_heavy

Review literature is very dense relative to primary central evidence.

Primary central evidence

12 papers
Akkermansia muciniphila-derived extracellular vesicles influence gut permeability through the regulation of tight junctions.
2018
Experimental & molecular medicine
Direct disease-relevant human paper with strong clinical, biomarker, or mechanistic framing.
Exercise Training Modulates Gut Microbiota Profile and Improves Endotoxemia.
2020
Medicine and science in sports and exercise
Direct disease-relevant human paper with strong clinical, biomarker, or mechanistic framing.
Serum zonulin levels in type 2 diabetes patients with diabetic kidney disease.
2021
Endokrynologia Polska
Direct disease-relevant human paper with strong clinical, biomarker, or mechanistic framing.
Morchella esculenta mushroom polysaccharide attenuates diabetes and modulates intestinal permeability and gut microbiota in a type 2 diabetic mice model.
2022
Frontiers in nutrition
Direct disease-relevant human paper with strong clinical, biomarker, or mechanistic framing.
Increased intestinal-fatty acid binding protein in obesity-associated type 2 diabetes mellitus.
2023
PloS one
Direct disease-relevant human paper with strong clinical, biomarker, or mechanistic framing.
High-fiber diet ameliorates gut microbiota, serum metabolism and emotional mood in type 2 diabetes patients.
2023
Frontiers in cellular and infection microbiology
Direct disease-relevant human paper with strong clinical, biomarker, or mechanistic framing.
Jiang-Tang-San-Huang pill alleviates type 2 diabetes mellitus through modulating the gut microbiota and bile acids metabolism.
2023
Phytomedicine : international journal of phytotherapy and phytopharmacology
Direct disease-relevant human paper with strong clinical, biomarker, or mechanistic framing.
An Association Between the Intestinal Permeability Biomarker Zonulin and the Development of Diabetic Retinopathy in Type II Diabetes Mellitus.
2023
Turkish journal of ophthalmology
Direct disease-relevant human paper with strong clinical, biomarker, or mechanistic framing.
Design and rationale for the SIB trial: a randomized parallel comparison of semaglutide versus placebo on intestinal barrier function in type 2 diabetes mellitus.
2023
Therapeutic advances in endocrinology and metabolism
Direct disease-relevant human paper with strong clinical, biomarker, or mechanistic framing.
Effectiveness of rifaximin and probiotics for the correction of intestinal permeability in patients with metabolic-associated fatty liver disease in combination with type 2 diabetes mellitus.
2024
Wiadomosci lekarskie (Warsaw, Poland : 1960)
Direct disease-relevant human paper with strong clinical, biomarker, or mechanistic framing.
Biomarkers of oxidation, inflammation and intestinal permeability in persons with diabetes mellitus with parenteral nutrition: A multicenter randomized trial.
2025
Clinical nutrition (Edinburgh, Scotland)
Direct disease-relevant human paper with strong clinical, biomarker, or mechanistic framing.
Indole-3-propionic acid links gut dysfunction to diabetic retinopathy: a biomarker and novel therapeutic approach.
2026
Gut
Direct disease-relevant human paper with strong clinical, biomarker, or mechanistic framing.

Supporting primary evidence

5 papers
Metabolic syndrome, metabolic comorbid conditions and risk of early-onset colorectal cancer.
2021
Gut
Human primary paper with plausible association relevance to the disease context.
Expression of Cholecystokinin and its Receptors in the Intestinal Tract of Type 2 Diabetes Patients and Healthy Controls.
2021
The Journal of clinical endocrinology and metabolism
Human primary paper with plausible association relevance to the disease context.
Expression of Neurotensin and Its Receptors Along the Intestinal Tract in Type 2 Diabetes Patients and Healthy Controls.
2023
The Journal of clinical endocrinology and metabolism
Human primary paper with plausible association relevance to the disease context.
Individuals with type 2 diabetes have higher density of small intestinal neurotensin-expressing cells.
2023
Molecular and cellular biochemistry
Human primary paper with plausible association relevance to the disease context.
A specific gut microbiota signature is associated with an enhanced GLP-1 and GLP-2 secretion and improved metabolic control in patients with type 2 diabetes after metabolic Roux-en-Y gastric bypass.
2023
Frontiers in endocrinology
Human primary paper with plausible association relevance to the disease context.

Preclinical supporting evidence

14 papers
Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice.
2008
Diabetes
Disease-relevant preclinical or model-based paper useful as supporting evidence.
A metagenome-wide association study of gut microbiota in type 2 diabetes.
2012
Nature
Disease-relevant preclinical or model-based paper useful as supporting evidence.
Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology.
2016
Gut
Disease-relevant preclinical or model-based paper useful as supporting evidence.
Increased intestinal permeability as a risk factor for type 2 diabetes.
2017
Diabetes & metabolism
Disease-relevant preclinical or model-based paper useful as supporting evidence.
A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice.
2017
Nature medicine
Disease-relevant preclinical or model-based paper useful as supporting evidence.
Healthspan and lifespan extension by fecal microbiota transplantation into progeroid mice.
2019
Nature medicine
Disease-relevant preclinical or model-based paper useful as supporting evidence.
GDF15 mediates the effects of metformin on body weight and energy balance.
2020
Nature
Disease-relevant preclinical or model-based paper useful as supporting evidence.
Metabolic endotoxemia promotes neuroinflammation after focal cerebral ischemia.
2020
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
Disease-relevant preclinical or model-based paper useful as supporting evidence.
Suppressing the intestinal farnesoid X receptor/sphingomyelin phosphodiesterase 3 axis decreases atherosclerosis.
2021
The Journal of clinical investigation
Disease-relevant preclinical or model-based paper useful as supporting evidence.
Decreased expression of the NLRP6 inflammasome is associated with increased intestinal permeability and inflammation in obesity with type 2 diabetes.
2024
Cellular and molecular life sciences : CMLS
Disease-relevant preclinical or model-based paper useful as supporting evidence.
Interactions between Age-Related Type 2 Diabetes and the Small Intestine.
2024
Biological & pharmaceutical bulletin
Disease-relevant preclinical or model-based paper useful as supporting evidence.
Carrageenan and insulin resistance in humans: a randomised double-blind cross-over trial.
2024
BMC medicine
Disease-relevant preclinical or model-based paper useful as supporting evidence.
Intestinal neutrophil extracellular traps promote gut barrier damage exacerbating endotoxaemia, systemic inflammation and progression of diabetic retinopathy in type 2 diabetes.
2025
Diabetologia
Disease-relevant preclinical or model-based paper useful as supporting evidence.
Mulberry leaf improves type 2 diabetes in mice via gut microbiota-SCFAs-GPRs axis and AMPK signaling pathway.
2025
Phytomedicine : international journal of phytotherapy and phytopharmacology
Disease-relevant preclinical or model-based paper useful as supporting evidence.

Review supporting evidence

63 papers
Leaky gut and diabetes mellitus: what is the link?
2011
Obesity reviews : an official journal of the International Association for the Study of Obesity
Relevant review or meta-analysis for the signal-disease area.
Type 2 diabetes mellitus: a possible surgically reversible intestinal dysfunction.
2012
Obesity surgery
Relevant review or meta-analysis for the signal-disease area.
Gut microbiota, probiotics and diabetes.
2014
Nutrition journal
Relevant review or meta-analysis for the signal-disease area.
The gut microbiome.
2014
Inflammation & allergy drug targets
Relevant review or meta-analysis for the signal-disease area.
Intestinal microbiota and type 2 diabetes: from mechanism insights to therapeutic perspective.
2014
World journal of gastroenterology
Relevant review or meta-analysis for the signal-disease area.
Metformin and the gastrointestinal tract.
2016
Diabetologia
Relevant review or meta-analysis for the signal-disease area.
Linking Gut Microbiota and Inflammation to Obesity and Insulin Resistance.
2016
Physiology (Bethesda, Md.)
Relevant review or meta-analysis for the signal-disease area.
Intestinal Microbiota in Type 2 Diabetes and Chronic Kidney Disease.
2017
Current diabetes reports
Relevant review or meta-analysis for the signal-disease area.
Gut Microbiota in Cardiovascular Health and Disease.
2017
Circulation research
Relevant review or meta-analysis for the signal-disease area.
Type 2 Diabetes and Bacteremia.
2017
Annals of nutrition & metabolism
Relevant review or meta-analysis for the signal-disease area.
Probiotics, prebiotics, synbiotics and insulin sensitivity.
2018
Nutrition research reviews
Relevant review or meta-analysis for the signal-disease area.
Probiotic strains and mechanistic insights for the treatment of type 2 diabetes.
2017
Endocrine
Relevant review or meta-analysis for the signal-disease area.
An update on the pathogenesis of cholesterol gallstone disease.
2018
Current opinion in gastroenterology
Relevant review or meta-analysis for the signal-disease area.
Microbial Regulation of Glucose Metabolism and Insulin Resistance.
2017
Genes
Relevant review or meta-analysis for the signal-disease area.
Increased Intestinal Permeability and Decreased Barrier Function: Does It Really Influence the Risk of Inflammation?
2016
Inflammatory intestinal diseases
Relevant review or meta-analysis for the signal-disease area.
Development of SGLT1 and SGLT2 inhibitors.
2018
Diabetologia
Relevant review or meta-analysis for the signal-disease area.
Altered Gut Microbiota in Type 2 Diabetes: Just a Coincidence?
2018
Current diabetes reports
Relevant review or meta-analysis for the signal-disease area.
Dietary metabolism, the gut microbiome, and heart failure.
2019
Nature reviews. Cardiology
Relevant review or meta-analysis for the signal-disease area.
Yogurt and other fermented foods as sources of health-promoting bacteria.
2018
Nutrition reviews
Relevant review or meta-analysis for the signal-disease area.
Dietary compounds and traditional Chinese medicine ameliorate type 2 diabetes by modulating gut microbiota.
2019
Critical reviews in food science and nutrition
Relevant review or meta-analysis for the signal-disease area.
Gut microbial metabolites in obesity, NAFLD and T2DM.
2019
Nature reviews. Endocrinology
Relevant review or meta-analysis for the signal-disease area.
The links between the gut microbiome and non-alcoholic fatty liver disease (NAFLD).
2019
Cellular and molecular life sciences : CMLS
Relevant review or meta-analysis for the signal-disease area.
The intestinal microbiota fuelling metabolic inflammation.
2020
Nature reviews. Immunology
Relevant review or meta-analysis for the signal-disease area.
The gut microbiome and metabolic syndrome.
2019
The Journal of clinical investigation
Relevant review or meta-analysis for the signal-disease area.
Gut Microbiome, Intestinal Permeability, and Tissue Bacteria in Metabolic Disease: Perpetrators or Bystanders?
2020
Nutrients
Relevant review or meta-analysis for the signal-disease area.
Influence of the Intestinal Microbiota on Diabetes Management.
2020
Current pharmaceutical biotechnology
Relevant review or meta-analysis for the signal-disease area.
The Effects of Type 2 Diabetes Mellitus on Organ Metabolism and the Immune System.
2020
Frontiers in immunology
Relevant review or meta-analysis for the signal-disease area.
Intestinal microbial metabolites in human metabolism and type 2 diabetes.
2020
Diabetologia
Relevant review or meta-analysis for the signal-disease area.
Gut Microbiota and Immune System Interactions.
2020
Microorganisms
Relevant review or meta-analysis for the signal-disease area.
Gut Microbiota as a Trigger for Metabolic Inflammation in Obesity and Type 2 Diabetes.
2020
Frontiers in immunology
Relevant review or meta-analysis for the signal-disease area.
Therapeutic mechanisms of traditional Chinese medicine to improve metabolic diseases via the gut microbiota.
2021
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
Relevant review or meta-analysis for the signal-disease area.
Microbiota-derived extracellular vesicles and metabolic syndrome.
2021
Acta physiologica (Oxford, England)
Relevant review or meta-analysis for the signal-disease area.
Role of the gut microbiota in type 2 diabetes and related diseases.
2021
Metabolism: clinical and experimental
Relevant review or meta-analysis for the signal-disease area.
Gut microbiome, prebiotics, intestinal permeability and diabetes complications.
2021
Best practice & research. Clinical endocrinology & metabolism
Relevant review or meta-analysis for the signal-disease area.
The Relationship between the Gut Microbiome and Metformin as a Key for Treating Type 2 Diabetes Mellitus.
2021
International journal of molecular sciences
Relevant review or meta-analysis for the signal-disease area.
Intestine-liver crosstalk in Type 2 Diabetes and non-alcoholic fatty liver disease.
2021
Metabolism: clinical and experimental
Relevant review or meta-analysis for the signal-disease area.
The Role of the Gut Microbiota in the Pathogenesis of Diabetes.
2022
International journal of molecular sciences
Relevant review or meta-analysis for the signal-disease area.
Gut microbiome and health: mechanistic insights.
2022
Gut
Relevant review or meta-analysis for the signal-disease area.
Dietary macronutrients and the gut microbiome: a precision nutrition approach to improve cardiometabolic health.
2022
Gut
Relevant review or meta-analysis for the signal-disease area.
Intestinal Barrier Function and Immune Homeostasis Are Missing Links in Obesity and Type 2 Diabetes Development.
2021
Frontiers in endocrinology
Relevant review or meta-analysis for the signal-disease area.
Gut Microbiota and Short Chain Fatty Acids: Implications in Glucose Homeostasis.
2022
International journal of molecular sciences
Relevant review or meta-analysis for the signal-disease area.
The human microbiome in disease and pathology.
2022
APMIS : acta pathologica, microbiologica, et immunologica Scandinavica
Relevant review or meta-analysis for the signal-disease area.
Diet-gut microbiota-epigenetics in metabolic diseases: From mechanisms to therapeutics.
2022
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
Relevant review or meta-analysis for the signal-disease area.
Gut microbiota: A new target for T2DM prevention and treatment.
2022
Frontiers in endocrinology
Relevant review or meta-analysis for the signal-disease area.
The role of Mediterranean diet and gut microbiota in type-2 diabetes mellitus associated with obesity (diabesity).
2022
Journal of preventive medicine and hygiene
Relevant review or meta-analysis for the signal-disease area.
Human milk oligosaccharides as prebiotics.
2023
Pediatrics and neonatology
Relevant review or meta-analysis for the signal-disease area.
Gut Microbiota and Cardiovascular Disease: Evidence on the Metabolic and Inflammatory Background of a Complex Relationship.
2023
International journal of molecular sciences
Relevant review or meta-analysis for the signal-disease area.
Type 2 Diabetes Mellitus and Liver Disease: Across the Gut-Liver Axis from Fibrosis to Cancer.
2023
Nutrients
Relevant review or meta-analysis for the signal-disease area.
The therapeutic potential of purified cannabidiol.
2023
Journal of cannabis research
Relevant review or meta-analysis for the signal-disease area.
The intestine as an endocrine organ and the role of gut hormones in metabolic regulation.
2023
Nature reviews. Gastroenterology & hepatology
Relevant review or meta-analysis for the signal-disease area.
Immunomodulatory effects of inulin and its intestinal metabolites.
2023
Frontiers in immunology
Relevant review or meta-analysis for the signal-disease area.
Berberine-induced glucagon-like peptide-1 and its mechanism for controlling type 2 diabetes mellitus: a comprehensive pathway review.
2024
Archives of physiology and biochemistry
Relevant review or meta-analysis for the signal-disease area.
Gut microbiota and therapy for obesity and type 2 diabetes.
2024
Frontiers in endocrinology
Relevant review or meta-analysis for the signal-disease area.
Incretin hormones, obesity and gut microbiota.
2024
Peptides
Relevant review or meta-analysis for the signal-disease area.
The central role of the gut microbiota in the pathophysiology and management of type 2 diabetes.
2024
Cell host & microbe
Relevant review or meta-analysis for the signal-disease area.
Exploring the Long-Term Effect of Artificial Sweeteners on Metabolic Health.
2024
Cureus
Relevant review or meta-analysis for the signal-disease area.
Targeting the Gut Microbiota for Prevention and Management of Type 2 Diabetes.
2024
Nutrients
Relevant review or meta-analysis for the signal-disease area.
Microbiota and Inflammatory Markers: A Review of Their Interplay, Clinical Implications, and Metabolic Disorders.
2025
International journal of molecular sciences
Relevant review or meta-analysis for the signal-disease area.
A Cascade of Microbiota-Leaky Gut-Inflammation- Is it a Key Player in Metabolic Disorders?
2025
Current obesity reports
Relevant review or meta-analysis for the signal-disease area.
Gut microbiome research: Revealing the pathological mechanisms and treatment strategies of type 2 diabetes.
2025
Diabetes, obesity & metabolism
Relevant review or meta-analysis for the signal-disease area.
Effect of Sodium Butyrate Supplementation on Type 2 Diabetes-Literature Review.
2025
Nutrients
Relevant review or meta-analysis for the signal-disease area.
Gut Microbiota in Exercise-Regulated Development, Progression, and Management of Type 2 Diabetes Mellitus: A Review of the Role and Mechanisms.
2025
Medical science monitor : international medical journal of experimental and clinical research
Relevant review or meta-analysis for the signal-disease area.
Gut microbiota-mediated metabolic dysregulation in type 2 diabetes and metabolic syndrome: emerging therapeutic targets beyond glycaemic control.
2026
Diabetes research and clinical practice
Relevant review or meta-analysis for the signal-disease area.