Dietary compounds and traditional Chinese medicine ameliorate type 2 diabetes by modulating gut microbiota

Abstract Diabetes mellitus (DM) and its complications are major public health concerns which strongly influence the quality of humans’ life. Modification of gut microbiota has been widely used for the management of diabetes. In this review, the relationship between diabetes and gut microbiota, as well as the effects of different dietary components and traditional Chinese medicine (TCM) on gut microflora are summarized. Dietary compounds and TCM possessing bioactive components (fiber and phytochemicals) first change the composition of gut microbiota (inhibiting pathogens and promoting the beneficial bacteria growth) and then influence the production of their metabolites, which would further modify the intestinal environment through inhibiting the production of detrimental compounds (such as lipopolysaccharide, hydrogen sulfide, indol, etc.). Importantly, metabolites (short chain fatty acids and other bioactive components) fermented/degraded by gut microbiota can target multiple pathways in intestine, liver, pancreas, etc., resulting in the improvement of gut health, glycemic control, lipids profile, insulin resistance and inflammation. Furthermore, understanding the interaction between different dietary components and gut microbiota, as well as underlying mechanisms would help design different diet formula for the management of diabetes. Further researches could focus on the combination of different dietary components for preventing and treating diabetes, based on the principle of “multiple components against multiple targets” from the perspective of gut microbiota.

[1]  S. Karboune,et al.  Digestibility and prebiotic properties of potato rhamnogalacturonan I polysaccharide and its galactose-rich oligosaccharides/oligomers. , 2016, Carbohydrate polymers.

[2]  X. Tong,et al.  Prevention of Type 2 Diabetes with the Chinese Herbal Medicine Tianqi Capsule: A Systematic Review and Meta-Analysis , 2016, Diabetes Therapy.

[3]  S. Massart,et al.  Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa , 2010, Proceedings of the National Academy of Sciences.

[4]  Chenhong Zhang,et al.  Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes , 2018, Science.

[5]  Jeong-Yeh Yang,et al.  Enhanced inhibition of adipogenesis and induction of apoptosis in 3T3-L1 adipocytes with combinations of resveratrol and quercetin. , 2008, Life sciences.

[6]  J. Laparra,et al.  Interactions of gut microbiota with functional food components and nutraceuticals. , 2010, Pharmacological research.

[7]  Lawrence A. David,et al.  Diet rapidly and reproducibly alters the human gut microbiome , 2013, Nature.

[8]  Zhi-xiang Shen,et al.  Dissection of mechanisms of Chinese medicinal formula Realgar-Indigo naturalis as an effective treatment for promyelocytic leukemia , 2008, Proceedings of the National Academy of Sciences.

[9]  Jacques Schrenzel,et al.  Responses of Gut Microbiota and Glucose and Lipid Metabolism to Prebiotics in Genetic Obese and Diet-Induced Leptin-Resistant Mice , 2011, Diabetes.

[10]  Young Min Cho,et al.  Rapidly increasing diabetes-related mortality with socio-environmental changes in South Korea during the last two decades. , 2006, Diabetes research and clinical practice.

[11]  N. de Kimpe,et al.  Natural medicines used in the traditional Chinese medical system for therapy of diabetes mellitus. , 2004, Journal of ethnopharmacology.

[12]  E. Feskens,et al.  Dietary fibre and incidence of type 2 diabetes in eight European countries: the EPIC-InterAct Study and a meta-analysis of prospective studies , 2015, Diabetologia.

[13]  E. Levy,et al.  A polyphenol-rich cranberry extract protects from diet-induced obesity, insulin resistance and intestinal inflammation in association with increased Akkermansia spp. population in the gut microbiota of mice , 2014, Gut.

[14]  J. Parkhill,et al.  Dominant and diet-responsive groups of bacteria within the human colonic microbiota , 2011, The ISME Journal.

[15]  Elisabeth M. Bik,et al.  Distinct Distal Gut Microbiome Diversity and Composition in Healthy Children from Bangladesh and the United States , 2013, PloS one.

[16]  S. Fava Glucagon-like peptide 1 and the cardiovascular system. , 2014, Current diabetes reviews.

[17]  P. Raskin,et al.  Report of the expert committee on the diagnosis and classification of diabetes mellitus. , 1999, Diabetes care.

[18]  F. Bäckhed,et al.  Microbiota-Generated Metabolites Promote Metabolic Benefits via Gut-Brain Neural Circuits , 2014, Cell.

[19]  F. Bäckhed,et al.  Dietary Fiber-Induced Improvement in Glucose Metabolism Is Associated with Increased Abundance of Prevotella. , 2015, Cell metabolism.

[20]  F. Bäckhed,et al.  The gut microbiota and metabolic disease: current understanding and future perspectives , 2016, Journal of internal medicine.

[21]  Karin Kraft,et al.  [Type-2 diabetes]. , 2010, MMW Fortschritte der Medizin.

[22]  W. D. de Vos,et al.  Akkermansia muciniphila and its role in regulating host functions. , 2017, Microbial pathogenesis.

[23]  野村栄一,et al.  2 , 1900, The Hatak Witches.

[24]  J. Clemente,et al.  Diet Drives Convergence in Gut Microbiome Functions Across Mammalian Phylogeny and Within Humans , 2011, Science.

[25]  A. Lee,et al.  Plasma concentrations of coffee polyphenols and plasma biomarkers of diabetes risk in healthy Japanese women , 2016, Nutrition & Diabetes.

[26]  R. Lamuela-Raventós,et al.  Intake of Total Polyphenols and Some Classes of Polyphenols Is Inversely Associated with Diabetes in Elderly People at High Cardiovascular Disease Risk. , 2015, The Journal of nutrition.

[27]  A. Duffy,et al.  Factors Influencing the Gut Microbiota, Inflammation, and Type 2 Diabetes. , 2017, The Journal of nutrition.

[28]  Xinli Li,et al.  Effects of Maydis stigma polysaccharide on the intestinal microflora in type-2 diabetes , 2016, Pharmaceutical biology.

[29]  S. Boytsov,et al.  Association between the gut microbiota and diet: Fetal life, early childhood, and further life. , 2016, Nutrition.

[30]  T. Consortium Dietary fibre and incidence of type 2 diabetes in eight European countries: the EPIC-InterAct Study and a meta-analysis of prospective studies , 2015 .

[31]  P. Franks,et al.  Lifestyle and precision diabetes medicine: will genomics help optimise the prediction, prevention and treatment of type 2 diabetes through lifestyle therapy? , 2017, Diabetologia.

[32]  C. Fu,et al.  Study on intestinal absorption and pharmacokinetic characterization of diester diterpenoid alkaloids in precipitation derived from fuzi-gancao herb-pair decoction for its potential interaction mechanism investigation. , 2013, Journal of ethnopharmacology.

[33]  R. Puupponen-Pimiä,et al.  Berry phenolics selectively inhibit the growth of intestinal pathogens , 2005, Journal of applied microbiology.

[34]  P. Sroka,et al.  Interaction of dietary compounds, especially polyphenols, with the intestinal microbiota: a review , 2015, European Journal of Nutrition.

[35]  Youfang Cao,et al.  Interactions between gut microbiota, host genetics and diet relevant to development of metabolic syndromes in mice , 2010, The ISME Journal.

[36]  Jie Yu,et al.  Intake of total saponins and polysaccharides from Polygonatum kingianum affects the gut microbiota in diabetic rats. , 2017, Phytomedicine : international journal of phytotherapy and phytopharmacology.

[37]  A. Agil,et al.  Melatonin improves glucose homeostasis in young Zucker diabetic fatty rats , 2012, Journal of pineal research.

[38]  L. Wen,et al.  The role of gut microbiota in the development of type 1, type 2 diabetes mellitus and obesity , 2015, Reviews in Endocrine and Metabolic Disorders.

[39]  Xinli Li,et al.  Effects of polysaccharide from Physalis alkekengi var. francheti on liver injury and intestinal microflora in type-2 diabetic mice , 2017, Pharmaceutical biology.

[40]  F. Tinahones,et al.  Benefits of polyphenols on gut microbiota and implications in human health. , 2013, The Journal of nutritional biochemistry.

[41]  Harry J Flint,et al.  The role of pH in determining the species composition of the human colonic microbiota. , 2009, Environmental microbiology.

[42]  Jianbo Xiao,et al.  Dietary polyphenols and type 2 diabetes: Human Study and Clinical Trial , 2018, Critical reviews in food science and nutrition.

[43]  P. Bork,et al.  A human gut microbial gene catalogue established by metagenomic sequencing , 2010, Nature.

[44]  E. Paschetta,et al.  Altered Gut Microbiota in Type 2 Diabetes: Just a Coincidence? , 2018, Current Diabetes Reports.

[45]  S B Roberts,et al.  Dietary fiber and weight regulation. , 2009, Nutrition reviews.

[46]  Xiexin Tang improves the symptom of type 2 diabetic rats by modulation of the gut microbiota , 2018, Scientific Reports.

[47]  F. Bäckhed,et al.  Reduced obesity, diabetes, and steatosis upon cinnamon and grape pomace are associated with changes in gut microbiota and markers of gut barrier. , 2018, American journal of physiology. Endocrinology and metabolism.

[48]  Vishal Sharma,et al.  Diabetes in Asia , 2010, The Lancet.

[49]  T. J. Wiles,et al.  Origins and virulence mechanisms of uropathogenic Escherichia coli. , 2008, Experimental and molecular pathology.

[50]  Hong Xiang,et al.  ZiBuPiYin recipe improves cognitive decline by regulating gut microbiota in Zucker diabetic fatty rats , 2017, Oncotarget.

[51]  J. Shaw,et al.  IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045. , 2018, Diabetes research and clinical practice.

[52]  J. Bressan,et al.  Melatonin intake and potential chronobiological effects on human health , 2019, Critical reviews in food science and nutrition.

[53]  K. Narayan,et al.  Prevention of type 2 diabetes , 2001, BMJ : British Medical Journal.

[54]  K. Svenson,et al.  Diet dominates host genotype in shaping the murine gut microbiota. , 2015, Cell host & microbe.

[55]  Yuguang Du,et al.  Chitosan oligosaccharides improve the disturbance in glucose metabolism and reverse the dysbiosis of gut microbiota in diabetic mice. , 2018, Carbohydrate polymers.

[56]  2. Classification and Diagnosis of Diabetes , 2016, Diabetes Care.

[57]  M. Li,et al.  Structural Changes of Gut Microbiota during Berberine-Mediated Prevention of Obesity and Insulin Resistance in High-Fat Diet-Fed Rats , 2012, PloS one.

[58]  L. Ferguson,et al.  Role of gut microbiota in , 2009 .

[59]  K. Kristiansen,et al.  Interplay between food and gut microbiota in health and disease. , 2019, Food research international.

[60]  Jun Xu,et al.  Understanding the Molecular Mechanisms of the Interplay Between Herbal Medicines and Gut Microbiota , 2017, Medicinal research reviews.

[61]  Jianping Ye,et al.  Berberine Improves Glucose Metabolism in Diabetic Rats by Inhibition of Hepatic Gluconeogenesis , 2011, PloS one.

[62]  Jianbo Xiao,et al.  Dietary polyphenols and type 2 diabetes: current insights and future perspectives. , 2014, Current medicinal chemistry.

[63]  H. T. Park,et al.  Akkermansia muciniphila-derived extracellular vesicles influence gut permeability through the regulation of tight junctions , 2018, Experimental & Molecular Medicine.

[64]  P. Wilmes,et al.  A Dietary Fiber-Deprived Gut Microbiota Degrades the Colonic Mucus Barrier and Enhances Pathogen Susceptibility , 2016, Cell.

[65]  L. Fan,et al.  Polysaccharide from Plantago asiatica L. attenuates hyperglycemia, hyperlipidemia and affects colon microbiota in type 2 diabetic rats , 2017, Food Hydrocolloids.

[66]  Anushka Patel Patients with Type 2 Diabetes , 2014 .

[67]  C. Sokhna,et al.  Gut microbiota diversity according to dietary habits and geographical provenance , 2018 .

[68]  R. Andridge,et al.  The flavonoid, naringenin, decreases adipose tissue mass and attenuates ovariectomy-associated metabolic disturbances in mice , 2015, Nutrition & Metabolism.

[69]  An Pan,et al.  Red meat consumption and risk of type 2 diabetes: 3 cohorts of US adults and an updated meta-analysis. , 2011, The American journal of clinical nutrition.

[70]  P. Teissèdre,et al.  Grape Polyphenols’ Effects in Human Cardiovascular Diseases and Diabetes , 2017, Molecules.

[71]  N. Okamura,et al.  The influence of rhein 8-O-β-D-glucopyranoside on the purgative action of sennoside A from rhubarb in mice. , 2012, Biological & pharmaceutical bulletin.

[72]  Eun-Jin Park,et al.  Strict vegetarian diet improves the risk factors associated with metabolic diseases by modulating gut microbiota and reducing intestinal inflammation. , 2013, Environmental microbiology reports.

[73]  Liping Zhao,et al.  Structural Alteration of Gut Microbiota during the Amelioration of Human Type 2 Diabetes with Hyperlipidemia by Metformin and a Traditional Chinese Herbal Formula: a Multicenter, Randomized, Open Label Clinical Trial , 2018, mBio.

[74]  Yonggong Zhai,et al.  Melatonin prevents obesity through modulation of gut microbiota in mice , 2017, Journal of pineal research.

[75]  L. Petit,et al.  Clostridium perfringens: toxinotype and genotype. , 1999, Trends in microbiology.

[76]  A. Lovegrove,et al.  In vitro fermentability of xylo-oligosaccharide and xylo-polysaccharide fractions with different molecular weights by human faecal bacteria. , 2018, Carbohydrate polymers.

[77]  Bernard Henrissat,et al.  The abundance and variety of carbohydrate-active enzymes in the human gut microbiota , 2013, Nature Reviews Microbiology.

[78]  Tian-Yu Zhao,et al.  Application of Berberine on Treating Type 2 Diabetes Mellitus , 2015, International journal of endocrinology.

[79]  L. Fan,et al.  Arabinoxylan Attenuates Type 2 Diabetes by Improvement of Carbohydrate, Lipid, and Amino Acid Metabolism , 2018, Molecular nutrition & food research.

[80]  W. Pan,et al.  Vegetarian diet, change in dietary patterns, and diabetes risk: a prospective study , 2018, Nutrition & Diabetes.

[81]  F. Bushman,et al.  Linking Long-Term Dietary Patterns with Gut Microbial Enterotypes , 2011, Science.

[82]  J. Manson,et al.  Curbing the Diabetes Pandemic: The Need for Global Policy Solutions. , 2015, JAMA.

[83]  R. Bauer,et al.  Natural product agonists of peroxisome proliferator-activated receptor gamma (PPARγ): a review , 2014, Biochemical pharmacology.

[84]  M. Roizen Red meat consumption and risk of type 2 diabetes: 3 cohorts of US adults and an updated meta-analysis , 2012 .

[85]  Jun Xu,et al.  Gut microbiota-involved mechanisms in enhancing systemic exposure of ginsenosides by coexisting polysaccharides in ginseng decoction , 2016, Scientific Reports.

[86]  Patricio Rojas-Silva,et al.  Dietary Polyphenols Promote Growth of the Gut Bacterium Akkermansia muciniphila and Attenuate High-Fat Diet–Induced Metabolic Syndrome , 2015, Diabetes.

[87]  F. Bäckhed,et al.  From Dietary Fiber to Host Physiology: Short-Chain Fatty Acids as Key Bacterial Metabolites , 2016, Cell.

[88]  F. Luo,et al.  Dietary nutrition and gut microflora: A promising target for treating diseases , 2018 .

[89]  E. Alizadeh,et al.  The effects of sodium butyrate and inulin supplementation on angiotensin signaling pathway via promotion of Akkermansia muciniphila abundance in type 2 diabetes; A randomized, double-blind, placebo-controlled trial , 2017, Journal of cardiovascular and thoracic research.

[90]  R. Reiter,et al.  Melatonin ameliorates low‐grade inflammation and oxidative stress in young Zucker diabetic fatty rats , 2013, Journal of pineal research.

[91]  Baojun Xu,et al.  Antidiabetic properties of dietary flavonoids: a cellular mechanism review , 2015, Nutrition & Metabolism.

[92]  Vanessa Neveu,et al.  Systematic analysis of the content of 502 polyphenols in 452 foods and beverages: an application of the phenol-explorer database. , 2010, Journal of agricultural and food chemistry.

[93]  H. Aisa,et al.  Hypoglycemic effect of the polyphenols rich extract from Rose rugosa Thunb on high fat diet and STZ induced diabetic rats. , 2017, Journal of ethnopharmacology.

[94]  Rui Liu,et al.  Network Pharmacology Bridges Traditional Application and Modern Development of Traditional Chinese Medicine , 2015 .

[95]  Ji‐Hyun Lee,et al.  Flavonoids protect against cytokine-induced pancreatic beta-cell damage through suppression of nuclear factor kappaB activation. , 2007, Pancreas.

[96]  M. Xie,et al.  Antidiabetic Mechanism of Dietary Polysaccharides Based on Their Gastrointestinal Functions. , 2018, Journal of agricultural and food chemistry.

[97]  Xi Chen,et al.  Transforming berberine into its intestine-absorbable form by the gut microbiota , 2015, Scientific Reports.

[98]  Peilin Shi,et al.  Dietary quality among men and women in 187 countries in 1990 and 2010: a systematic assessment , 2015, The Lancet. Global health.

[99]  M. Xie,et al.  Metabolism and health effects of phyto-estrogens , 2017, Critical reviews in food science and nutrition.

[100]  J. Walter,et al.  The human gut microbiome: ecology and recent evolutionary changes. , 2011, Annual review of microbiology.

[101]  H. Chung,et al.  Oligonol, a low-molecular-weight polyphenol derived from lychee fruit, protects the pancreas from apoptosis and proliferation via oxidative stress in streptozotocin-induced diabetic rats. , 2016, Food & function.

[102]  C. Knauf,et al.  Selective increases of bifidobacteria in gut microflora improve high-fat-diet-induced diabetes in mice through a mechanism associated with endotoxaemia , 2007, Diabetologia.

[103]  R. Knight,et al.  The gut microbiota in human energy homeostasis and obesity , 2015, Trends in Endocrinology & Metabolism.

[104]  BOULIN,et al.  Classification and Diagnosis of Diabetes. , 2022, Primary care.

[105]  Y. Terauchi,et al.  Galacto-oligosaccharides ameliorate dysbiotic Bifidobacteriaceae decline in Japanese patients with type 2 diabetes. , 2017, Beneficial microbes.

[106]  B. Liu,et al.  Regulatory Efficacy of Brown Seaweed Lessonia nigrescens Extract on the Gene Expression Profile and Intestinal Microflora in Type 2 Diabetic Mice , 2018, Molecular nutrition & food research.

[107]  J. Most,et al.  Short-term supplementation with a specific combination of dietary polyphenols increases energy expenditure and alters substrate metabolism in overweight subjects , 2014, International Journal of Obesity.

[108]  Yongli Guo,et al.  Erratum to “The Feasibility of Xpert MTB/RIF Testing to Detect Rifampicin Resistance among Childhood Tuberculosis for Prevalence Surveys in Northern China” , 2017, BioMed research international.

[109]  Yuko Sakurai,et al.  Gut Dysbiosis and Detection of “Live Gut Bacteria” in Blood of Japanese Patients With Type 2 Diabetes , 2014, Diabetes Care.

[110]  L. Kong,et al.  High fructose diet-induced metabolic syndrome: Pathophysiological mechanism and treatment by traditional Chinese medicine. , 2018, Pharmacological research.

[111]  J. Shaw,et al.  Diabetes: a 21st century challenge. , 2014, The lancet. Diabetes & endocrinology.

[112]  D. Damin,et al.  THE THERAPEUTIC USE OF SYMBIOTICS , 2014, Arquivos brasileiros de cirurgia digestiva : ABCD = Brazilian archives of digestive surgery.

[113]  F. Bäckhed,et al.  Signals from the gut microbiota to distant organs in physiology and disease , 2016, Nature Medicine.

[114]  H. Tilg,et al.  Microbiota and diabetes: an evolving relationship , 2014, Gut.

[115]  Zhuye Jie,et al.  Human Gut Microbiota Changes Reveal the Progression of Glucose Intolerance , 2013, PloS one.

[116]  B. Liu,et al.  Bioactive compounds from marine macroalgae and their hypoglycemic benefits , 2018 .

[117]  E. Levy,et al.  Triggering Akkermansia with dietary polyphenols: A new weapon to combat the metabolic syndrome? , 2016, Gut microbes.

[118]  Li Liang,et al.  Pumpkin polysaccharide modifies the gut microbiota during alleviation of type 2 diabetes in rats. , 2018, International journal of biological macromolecules.

[119]  Xinhua Xiao,et al.  Inulin-type fructan improves diabetic phenotype and gut microbiota profiles in rats , 2018, PeerJ.

[120]  M. Haluzík,et al.  The role of adipose tissue immune cells in obesity and low-grade inflammation. , 2014, The Journal of endocrinology.

[121]  U. Ijaz,et al.  Host–microbiome interactions in human type 2 diabetes following prebiotic fibre (galacto-oligosaccharide) intake , 2016, British Journal of Nutrition.

[122]  Qiang Feng,et al.  A metagenome-wide association study of gut microbiota in type 2 diabetes , 2012, Nature.

[123]  W. Deng,et al.  Baicalein, a natural product, selectively activating AMPKα2 and ameliorates metabolic disorder in diet-induced mice , 2012, Molecular and Cellular Endocrinology.

[124]  Ying Wang Attenuation of berberine on lipopolysaccharide-induced inflammatory and apoptosis responses in β-cells via TLR4-independent JNK/NF-κB pathway , 2014, Pharmaceutical biology.

[125]  Lucie Geurts,et al.  Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity , 2013, Proceedings of the National Academy of Sciences.

[126]  J. Most,et al.  Short-term supplementation with a specific combination of dietary polyphenols increases energy expenditure and alters substrate metabolism in overweight subjects , 2014, International Journal of Obesity.

[127]  Na-Ri Shin,et al.  An increase in the Akkermansia spp. population induced by metformin treatment improves glucose homeostasis in diet-induced obese mice , 2013, Gut.

[128]  Liping Zhao,et al.  Structural modulation of gut microbiota during alleviation of type 2 diabetes with a Chinese herbal formula , 2014, The ISME Journal.

[129]  Kai-Fai Lee,et al.  Intestinal absorption and bioavailability of traditional Chinese medicines: a review of recent experimental progress and implication for quality control , 2013, The Journal of pharmacy and pharmacology.

[130]  S. Prapulla,et al.  Beneficial effect of xylo-oligosaccharides and fructo-oligosaccharides in streptozotocin-induced diabetic rats , 2010, British Journal of Nutrition.

[131]  W. Willett,et al.  Carbohydrate quality and quantity and risk of type 2 diabetes in US women. , 2015, The American journal of clinical nutrition.

[132]  M. Yeomans,et al.  Optimising foods for satiety , 2015 .

[133]  P. Clifton,et al.  Probiotics, prebiotics, synbiotics and insulin sensitivity , 2017, Nutrition Research Reviews.

[134]  S. Sørensen,et al.  Gut Microbiota in Human Adults with Type 2 Diabetes Differs from Non-Diabetic Adults , 2010, PloS one.

[135]  Eleazar Eskin,et al.  Genetic and environmental control of host-gut microbiota interactions , 2015, Genome research.

[136]  M. Johansson,et al.  The gastrointestinal mucus system in health and disease , 2013, Nature Reviews Gastroenterology &Hepatology.

[137]  B. Bartolomé,et al.  A Survey of Modulation of Gut Microbiota by Dietary Polyphenols , 2015, BioMed research international.

[138]  F. Milagro,et al.  Reshaping faecal gut microbiota composition by the intake of trans-resveratrol and quercetin in high-fat sucrose diet-fed rats. , 2015, The Journal of nutritional biochemistry.

[139]  D. Ojcius,et al.  Anti-obesogenic and antidiabetic effects of plants and mushrooms , 2017, Nature Reviews Endocrinology.

[140]  Zhaoping Li,et al.  Xylooligosaccharide supplementation alters gut bacteria in both healthy and prediabetic adults: a pilot study , 2015, Front. Physiol..

[141]  Xiyan Zhao,et al.  Prevention of type 2 diabetes with the traditional Chinese patent medicine: A systematic review and meta-analysis. , 2017, Diabetes research and clinical practice.

[142]  G. Mithieux Nutrient Control of Energy Homeostasis via Gut-Brain Neural Circuits , 2014, Neuroendocrinology.

[143]  Oluf Pedersen,et al.  The Gut Microbiota in Type 2 Diabetes , 2016 .

[144]  Ji‐Hyun Lee,et al.  Flavonoids Protect Against Cytokine-Induced Pancreatic β-Cell Damage Through Suppression of Nuclear Factor κB Activation , 2007 .

[145]  J. Nicholson,et al.  Host-Gut Microbiota Metabolic Interactions , 2012, Science.

[146]  K. Petersen,et al.  Acetate mediates a microbiome-brain-β cell axis promoting metabolic syndrome , 2016, Nature.

[147]  E. Zoetendal,et al.  Diet, microbiota, and microbial metabolites in colon cancer risk in rural Africans and African Americans. , 2013, The American journal of clinical nutrition.

[148]  Dan Zhu,et al.  Effects of Melatonin on Intestinal Microbiota and Oxidative Stress in Colitis Mice , 2018, BioMed research international.

[149]  Kee Seng Chia,et al.  Diabetes in Asia and the Pacific: Implications for the Global Epidemic , 2016, Diabetes Care.

[150]  Jian Zhang,et al.  Effects of Qijian mixture on type 2 diabetes assessed by metabonomics, gut microbiota and network pharmacology , 2018, Pharmacological research.