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The Synergism of Human Lactobacillaceae and Inulin Decrease Hyperglycemia via Regulating the Composition of Gut Microbiota and Metabolic Profiles in db/db Mice

  • Peifan Li (College of Biochemical Engineering, Beijing Union University) ;
  • Tong Tong (College of Biochemical Engineering, Beijing Union University) ;
  • Yusong Wu (College of Biochemical Engineering, Beijing Union University) ;
  • Xin Zhou (College of Biochemical Engineering, Beijing Union University) ;
  • Michael Zhang (Department of Physics and Astronomy, University of Manitoba) ;
  • Jia Liu (Internal Trade Food Science and Technology (Beijing) Co., Ltd) ;
  • Yongxin She (Institute of Quality Standard and Testing Technology for Agro-Products, Chinese Academy of Agricultural Science) ;
  • Zuming Li (College of Biochemical Engineering, Beijing Union University) ;
  • Yongli Li (Henan Provincial People's Hospital, People's Hospital of Zhengzhou University)
  • Received : 2023.04.24
  • Accepted : 2023.08.14
  • Published : 2023.12.28

Abstract

This study aimed to evaluate the effects of Limosilactobacillus fermentum and Lactiplantibacillus plantarum isolated from human feces coordinating with inulin on the composition of gut microbiota and metabolic profiles in db/db mice. These supplements were administered to db/db mice for 12 weeks. The results showed that the Lactobacillaceae coordinating with inulin group (LI) exhibited lower fasting blood glucose levels than the model control group (MC). Additionally, LI was found to enhance colon tissue and increase the levels of short-chain fatty acids. 16S rRNA sequencing revealed that the abundance of Corynebacterium and Proteus, which were significantly increased in the MC group compared with NC group, were significantly decreased by the treatment of LI that also restored the key genera of the Lachnospiraceae_NK4A136_group, Lachnoclostridium, Ruminococcus_gnavus_group, Desulfovibrio, and Lachnospiraceae_UCG-006. Untargeted metabolomics analysis showed that lotaustralin, 5-hydroxyindoleacetic acid, and 13(S)-HpODE were increased while L-phenylalanine and L-tryptophan were decreased in the MC group compared with the NC group. However, the intervention of LI reversed the levels of these metabolites in the intestine. Correlation analysis revealed that Lachnoclostridium and Ruminococcus_gnavus_group were negatively correlated with 5-hydroxyindoleacetic acid and 13(S)-HpODE, but positively correlated with L-tryptophan. 13(S)-HpODE was involved in the "linoleic acid metabolism". L-tryptophan and 5-hydroxyindoleacetic acid were involved in "tryptophan metabolism" and "serotonergic synapse". These findings suggest that LI may alleviate type 2 diabetes symptoms by modulating the abundance of Ruminococcus_gnavus_group and Lachnoclostridium to regulate the pathways of "linoleic acid metabolism", "serotonergic synapse", and" tryptophan metabolism". Our results provide new insights into prevention and treatment of type 2 diabetes.

Keywords

Acknowledgement

This work was supported by the [Natural Science Foundation of Beijing Municipality] under Grant [6173033]; [Academic Research Projects of Beijing Union University] under Grant [ZK70202003]; [Sino Canada health engineering research institute cooperation projects] under Grant [50304JA1901]; [Internal trade food science and technology (Beijing) Co., Ltd cooperation projects] under Grant [202116].

References

  1. Tucker AJ, Vandermey JS, Robinson LE, Graham TE, Bakovic M, Duncan AM. 2014. Effects of breads of varying carbohydrate quality on postprandial glycaemic, incretin and lipidaemic response after first and second meals in adults with diet-controlled type 2 diabetes. J. Funct. Foods 6: 116-125. 
  2. Woldeamlak B, Yirdaw K, Biadgo B. 2019. Role of gut microbiota in type 2 diabetes mellitus and its complications: Novel insights and Potential Intervention Strategies. Korean J. Gastroenterol. 74: 314. 
  3. Gilbert JA, Blaser MJ, Caporaso JG, Jansson JK, Lynch SV, Knight R. 2018. Current understanding of the human microbiome. Nat. Med. 24: 392-400. 
  4. Garber AJ, Abrahamson MJ, Barzilay JI, Blonde L, Bloomgarden ZT, Bush MA, et al. 2018. Consensus statement by the American association of clinical endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes management algorithm - 2018 executive summary. Endocr. Pract. 24: 91-121. 
  5. Santos-Marcos JA, Perez-Jimenez F, Camargo A. 2019. The role of diet and intestinal microbiota in the development of metabolic syndrome. J. Nutr. Biochem. 70: 1-27. 
  6. Everard A, Belzer C, Geurts L, Ouwerkerk JP, Druart C, Bindels LB, et al. 2013. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc. Nat. Acad. Sci. USA 110: 9066-9071. 
  7. Cani PD, Osto M, Geurts L, Everard A. 2012. Involvement of gut microbiota in the development of low-grade inflammation and type 2 diabetes associated with obesity. Gut Microbes 3: 279-288. 
  8. Xia Z, Han Y, Wang K, Guo S, Wu D, Huang X, et al. 2017. Oral administration of propionic acid during lactation enhances the colonic barrier function. Lipids Health Dis. 16: 62. 
  9. Kirpich IA, McClain CJ. 2012. Probiotics in the treatment of the liver diseases. J. Am. Coll. Nutr. 31: 14-23. 
  10. Salles BIM, Cioffi D, Ferreira SRG. 2020. Probiotics supplementation and insulin resistance: a systematic review. Diabetol. Metab. Syndr. 12: 98. 
  11. Vallianou N, Stratigou T, Christodoulatos GS, Tsigalou C, Dalamaga M. 2020. Probiotics, prebiotics, synbiotics, postbiotics, and obesity: current evidence, controversies, and perspectives. Curr. Obes. Rep. 9: 179-192. 
  12. Tian L, Zhao R, Xu X, Zhou Z, Xu X, Luo D, et al. 2023. Modulatory effects of Lactiplantibacillus plantarum on chronic metabolic diseases. Food Sci. Hum. Wellness 12: 959-974. 
  13. Toshimitsu T, Gotou A, Furuichi K, Hachimura S, Asami Y. 2019. Effects of 12-wk Lactobacillus plantarum OLL2712 treatment on glucose metabolism and chronic inflammation in prediabetic individuals: a single-arm pilot study. Nutrition 58: 175-180. 
  14. Wang G, Song J, Huang Y, Li X, Wang H, Zhang Y, et al. 2022. Lactobacillus plantarum SHY130 isolated from yak yogurt attenuates hyperglycemia in C57BL/6J mice by regulating the enteroinsular axis. Food Funct. 13: 675-687. 
  15. Kim JE, Lee JY, Kang C-H. 2022. Limosilactobacillus fermentum MG4295 improves hyperglycemia in high-fat diet-induced mice. Foods 11: 231. 
  16. Sun Q, Liu X, Zhang Y, Song Y, Ma X, Shi Y, et al. 2019. L. plantarum, L. fermentum, and B. breve beads modified the intestinal microbiota and alleviated the inflammatory response in high-fat diet-fed mice. Probiotics Antimicro. Proteins 12: 535-544. 
  17. Singh RS, Singh RP, Kennedy JF. 2016. Recent insights in enzymatic synthesis of fructooligosaccharides from inulin. Int. J. Biol. Macromol. 85: 565-572. 
  18. Rao M, Gao C, Xu L, Jiang L, Zhu J, Chen G, et al. 2019. Effect of inulin-type carbohydrates on insulin resistance in patients with type 2 diabetes and obesity: a systematic review and meta-analysis. J. Diabetes Res. 2019: 5101423. 
  19. Hosseinifard E-S, Morshedi M, Bavafa-Valenlia K, Saghafi-Asl M. 2019. The novel insight into anti-inflammatory and anxiolytic effects of psychobiotics in diabetic rats: possible link between gut microbiota and brain regions. Eur. J. Nutr. 58: 3361-3375. 
  20. Ning C, Wang X, Gao S, Mu J, Wang Y, Liu S, et al. 2017. Chicory inulin ameliorates type 2 diabetes mellitus and suppresses JNK and MAPK pathways in vivo and in vitro. Mol. Nutr. Food Res. 61: 1600673. 
  21. Liu Y, Li Y, Zhang W, Sun M, Zhang Z. 2019. Hypoglycemic effect of inulin combined with ganoderma lucidum polysaccharides in T2DM rats. J. Funct. Food 55: 381-390. 
  22. Li C, Cao J, Nie S-P, Zhu K-X, Xiong T, Xie M-Y. 2018. Serum metabolomics analysis for biomarker of Lactobacillus plantarum NCU116 on hyperlipidaemic rat model feed by high fat diet. J. Funct. Food 42: 171-176. 
  23. Guerreiro I, Oliva-Teles A, Enes P. 2015. Improved glucose and lipid metabolism in European sea bass (Dicentrarchus labrax) fed short-chain fructooligosaccharides and xylooligosaccharides. Aquaculture 441: 57-63. 
  24. Lu H, Liu P, Zhang X, Bao T, Wang T, Guo L, et al. 2021. Inulin and lycium barbarum polysaccharides ameliorate diabetes by enhancing gut barrier via modulating gut microbiota and activating gut mucosal TLR2+ intraepithelial γδ T cells in rats. J. Funct. Food 79: 104407. 
  25. Ning C, Wang X, Gao S, Mu J, Wang Y, Liu S, et al. 2017. Chicory inulin ameliorates type 2 diabetes mellitus and suppresses JNK and MAPK pathways in vivo and in vitro. Mol. Nutr. Food Res. 61: 1600673. 
  26. Wang Y. 2009. Prebiotics: present and future in food science and technology. Food Res. Int. 42: 8-12. 
  27. Takemura N, Hagio M, Ishizuka S, Ito H, Morita T, Sonoyama K. 2010. Inulin prolongs survival of intragastrically administered Lactobacillus plantarum No. 14 in the gut of mice fed a high-fat diet. J. Nutr. 140: 1963-1969. 
  28. Soto C. 2013. Lactobacillus plantarum as source of conjugated linoleic acid: effect of pH, incubation temperature and inulin incorporation. J. Biochem. Technol. 5: 649-653. 
  29. Fuhren J, Schwalbe M, Rosch C, Nijland R, Wels M, Schols HA, et al. 2021. Dietary inulin increases Lactiplantibacillus plantarum strain Lp900 persistence in rats depending on the dietary-calcium level. Appl. Environ. Microbiol 87: e001222-21. 
  30. Valenlia KB, Morshedi M, Saghafi-Asl M, Shahabi P, Abbasi MM. 2018. Beneficial impacts of Lactobacillus plantarum and inulin on hypothalamic levels of insulin, leptin, and oxidative markers in diabetic rats. J. Funct. Food 46: 529-537. 
  31. Gao H, Wen JJ, Hu JL, Nie QX, Chen HH, Xiong T, et al. 2018. Polysaccharide from fermented Momordica charantia L. with Lactobacillus plantarum NCU116 ameliorates type 2 diabetes in rats. Carbohydr. Polym. 201: 624-633. 
  32. Nagpal R, Wang S, Ahmadi S, Hayes J, Gagliano J, Subashchandrabose S, et al. 2018. Human-origin probiotic cocktail increases short-chain fatty acid production via modulation of mice and human gut microbiome. Sci. Rep. 8: 12649. 
  33. Baothman OA, Zamzami MA, Taher I, Abubaker J, Abu-Farha M. 2016. The role of gut microbiota in the development of obesity and diabetes. Lipids Health Dis. 15: 108. 
  34. Tai N, Wong FS, Wen L. 2015. The role of gut microbiota in the development of type 1, type 2 diabetes mellitus and obesity. Rev. Endocr. Metab. Disord 16: 55-65. 
  35. Zhang L, Li L, Pan X, Shi Z, Feng X, Gong B, et al. 2018. Enhanced growth and activities of the dominant functional microbiota of chicken manure composts in the presence of maize straw. Front. Microbiol. 9: 1131. 
  36. Ottman N, Davids M, Suarez-Diez M, Boeren S, Schaap PJ, Martins dos Santos VAP, et al. 2017. Genome-scale model and omics analysis of metabolic capacities of Akkermansia muciniphila reveal a preferential mucin-degrading lifestyle. Appl. Environ. Microbiol. 83: e01014-17. 
  37. Fujio-Vejar S, Vasquez Y, Morales P, Magne F, Vera-Wolf P, Ugalde JA, et al. 2017. The gut microbiota of healthy chilean subjects reveals a high abundance of the phylum Verrucomicrobia. Front. Microbiol. 8: 1221. 
  38. Nam Y, Yoon S, Baek J, Kim J-H, Park M, Hwang K, et al. 2022. Heat-killed Lactiplantibacillus plantarum LRCC5314 mitigates the effects of stress-related type 2 diabetes in mice via gut microbiome modulation. J. Microbiol. Biotechnol. 32: 324-332. 
  39. Jia T, Yun Y, Yu Z. 2021. Propionic acid and sodium benzoate affected biogenic amine formation, microbial community, and quality of oat silage. Front. Microbiol. 12: 750920. 
  40. Arora T, Backhed F. 2016. The gut microbiota and metabolic disease: current understanding and future perspectives. J. Intern. Med. 280: 339-349. 
  41. Million M, Angelakis E, Paul M, Armougom F, Leibovici L, Raoult D. 2012. Comparative meta-analysis of the effect of Lactobacillus species on weight gain in humans and animals. Microb. Pathog. 53: 100-108. 
  42. Ghosh TS, Arnoux J, O'Toole PW. 2020. Metagenomic analysis reveals distinct patterns of gut Lactobacillus prevalence, abundance, and geographical variation in health and disease. Gut Microbes 12: 1822729. 
  43. Song Y, Wu M, Tao G, Lu M, Lin J, Huang J. 2020. Feruloylated oligosaccharides and ferulic acid alter gut microbiome to alleviate diabetic syndrome. Food Res. Int. 137: 109410. 
  44. Karlsson FH, Tremaroli V, Nookaew I, Bergstrom G, Behre CJ, Fagerberg B, et al. 2013. Gut metagenome in European women with normal, impaired and diabetic glucose control. Nature 498: 99-103. 
  45. Vanegas SM, Meydani M, Barnett JB, Goldin B, Kane A, Rasmussen H, et al. 2017. Substituting whole grains for refined grains in a 6-wk randomized trial has a modest effect on gut microbiota and immune and inflammatory markers of healthy adults. Am. J. Clin. Nutr. 105: 635-650. 
  46. Boutard M, Cerisy T, Nogue PY, Alberti A, Weissenbach J, Salanoubat M, et al. 2014. Functional diversity of carbohydrate-active enzymes enabling a bacterium to ferment plant biomass. PLoS Genet. 10: e1004773. 
  47. Chen L, Gao Y, Zhao Y, Yang G, Wang C, Zhao Z, et al. 2022. Chondroitin sulfate stimulates the secretion of H2S by Desulfovibrio to improve insulin sensitivity in NAFLD mice. Int. J. Biol. Macromol. 213: 631-638. 
  48. Wang S, Hovland J, Brooks S, Bakke R. 2013. Detoxifying CO2 capture reclaimer waste by anaerobic digestion. Appl. Biochem. Biotechnol. 172: 776-783. 
  49. Jimenez M, Gil V, Martinez-Cutillas M, Mane N, Gallego D. 2017. Hydrogen sulphide as a signalling molecule regulating physiopathological processes in gastrointestinal motility. Br. J. Pharmacol. 174: 2805-2817. 
  50. Dash NR, Al Bataineh MT. 2020. Metagenomic analysis of the gut microbiome reveals enrichment of menaquinones (Vitamin K2) pathway in diabetes mellitus. Diabetes Metab. J. 45: 77-85. 
  51. Li H, Qi T, Huang Z, Ying Y, Zhang Y, Wang B, et al. 2017. Relationship between gut microbiota and type 2 diabetic erectile dysfunction in Sprague-Dawley rats. J. Huazhong Univ. Sci. Technol. Med. Sci. 37: 523-530. 
  52. Wang S, Guo C, Xing Z, Li M, Yang H, Zhang Y, et al. 2021. Dietary intervention with α-amylase inhibitor in white kidney beans added yogurt modulated gut microbiota to adjust blood glucose in mice. Front. Nutr. 8: 664976. 
  53. Chen M, Liao Z, Lu B, Wang M, Lin L, Zhang S, et al. 2018. Huang-Lian-Jie-Du-decoction ameliorates hyperglycemia and insulin resistant in association with gut microbiota modulation. Front. Microbiol. 9: 2380. 
  54. Chen R, Wu P, Cai Z, Fang Y, Zhou H, Lasanajak Y, et al. 2019. Puerariae lobatae radix with chuanxiong rhizoma for treatment of cerebral ischemic stroke by remodeling gut microbiota to regulate the brain-gut barriers. J. Nutr. Biochem. 65: 101-114. 
  55. Ma L, Ni Y, Wang Z, Tu W, Ni L, Zhuge F, et al. 2020. Spermidine improves gut barrier integrity and gut microbiota function in diet-induced obese mice. Gut Microbe 12: 1-19. 
  56. Peng M, Wang L, Su H, Zhang L, Yang Y, Sun L, et al. 2022. Ginsenoside Rg1 improved diabetes through regulating the intestinal microbiota in high-fat diet and streptozotocin-induced type 2 diabetes rats. J. Food Biochem. 46: e14321. 
  57. Deng J, Zou X, Liang Y, Zhong J, Zhou K, Zhang J, et al. 2023. Hypoglycemic effects of different molecular weight konjac glucomannans via intestinal microbiota and SCFAs mediated mechanism. Int. J. Biological Macromol. 234: 122941. 
  58. Zhao L, Zhang F, Ding X, Wu G, Lam YY, Wang X, et al. 2018. Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes. Science 359: 1151-1156. 
  59. Alamshah A, Spreckley E, Norton M, Kinsey-Jones JS, Amin A, Ramgulam A, et al. 2017. L-phenylalanine modulates gut hormone release and glucose tolerance, and suppresses food intake through the calcium-sensing receptor in rodents. Int. J. Obes. 41: 1693-1701. 
  60. Debnath S, Velagapudi C, Redus L, Thameem F, Kasinath B, Hura CE, et al. 2017. Tryptophan metabolism in patients with chronic kidney disease secondary to type 2 diabetes: relationship to inflammatory markers. Int. J. Tryptophan Res. 10: 117864691769460. 
  61. Bjarnholt N, Rook F, Motawia MS, Cornett C, Jorgensen C, Olsen CE, et al. 2008. Diversification of an ancient theme: hydroxynitrile glucosides. Phytochemistry 69: 1507-1516. 
  62. Kamalu BP. 1995. The adverse effects of long-term cassava (Manihot esculentaCrantz) consumption. Int. J. Food Sci. Nutr. 46: 65-93. 
  63. Takada A, Shimizu F, Takao T, Masuda J. 2018. Measurement of tryptophan metabolites in healthy old men and patients of type 2 diabetes mellitus (T2DM). Food Nutr. Sci. 09: 1206-1220. 
  64. Banimfreg BH, Shamayleh A, Alshraideh H, Semreen MH, Soares NC. 2022. Untargeted approach to investigating the metabolomics profile of type 2 diabetes emiratis. J. Proteomics 269: 104718. 
  65. Matsuoka K, Kato K, Takao T, Ogawa M, Ishii Y, Shimizu F, et al. 2016. Concentrations of various tryptophan metabolites are higher in patients with diabetes mellitus than in healthy aged male adults. Diabetol. Int. 8: 69-75. 
  66. Shao J, Liu Y, Wang H, Luo Y, Chen L. 2020. An integrated fecal microbiome and metabolomics in T2DM rats reveal antidiabetes effects from host-microbial metabolic axis of etoac extract from sophora flavescens. Oxidative Medicine Cell. Longev. 2020: 1-25. 
  67. Bennet H, Balhuizen A, Medina A, Dekker Nitert M, Ottosson Laakso E, Essen S, et al. 2015. Altered serotonin (5-HT) 1D and 2A receptor expression may contribute to defective insulin and glucagon secretion in human type 2 diabetes. Peptides 71: 113-120. 
  68. Cataldo Bascunan LR, Lyons C, Bennet H, Artner I, Fex M. 2018. Serotonergic regulation of insulin secretion. Acta Physiol. 225: e13101. 
  69. Eriksson O, Selvaraju RK, Johansson L, Eriksson JW, Sundin A, Antoni G, et al. 2014. Quantitative imaging of serotonergic biosynthesis and degradation in the endocrine pancreas. J. Nucl. Med. 55: 460-465. 
  70. Wei S, Wang J, Wang C, Wang Y, Jin M. 2022. Inulin mitigates high fructose-induced gut dysbiosis and metabolic dysfunction in mice. J. Funct. Foods 97: 105236. 
  71. Imamura F, Micha R, Wu JHY, de Oliveira Otto MC, Otite FO, Abioye AI, et al. 2016. Effects of saturated fat, polyunsaturated fat, monounsaturated fat, and carbohydrate on glucose-insulin homeostasis: a systematic review and meta-analysis of randomised controlled feeding trials. PLoS Med. 13: e1002087. 
  72. Wu JHY, Marklund M, Imamura F, Tintle N, Ardisson Korat AV, de Goede J, et al. 2017. Omega-6 fatty acid biomarkers and incident type 2 diabetes: pooled analysis of individual-level data for 39 740 adults from 20 prospective cohort studies. Lancet Diabetes Endocrinol. 5: 965-974. 
  73. Zhang C, Dong L, Wu J, Qiao S, Xu W, Ma S, et al. 2020. Intervention of resistant starch 3 on type 2 diabetes mellitus and its mechanism based on urine metabonomics by liquid chromatography-tandem mass spectrometry. Biomed. Pharmacother. 128: 110350. 
  74. Chung HI, Kim J, Kim JY, Kwon O. 2013. Acute intake of mulberry leaf aqueous extract affects postprandial glucose response after maltose loading: randomized double-blind placebo-controlled pilot study. J. Funct. Foods 5: 1502-1506. 
  75. Williams BB, Van Benschoten AH, Cimermancic P, Donia MS, Zimmermann M, Taketani M, et al. 2014. Discovery and characterization of gut microbiota decarboxylases that can produce the neurotransmitter tryptamine. Cell Host Microbe 16: 495-503. 
  76. Booij L. 2002. Predictors of mood response to acute tryptophan depletion a reanalysis. Neuropsychopharmacology 27: 852-861.