The interplay between Dendrobium Officinale polysaccharide, gut microbiota, and lipid metabolism in HFD/STZ-induced type 2 diabetic mice
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Keywords
Abstract
Dietary polysaccharides are effective in mitigating hyperglycemia, insulin resistance, and improving the condition of people with type 2 diabetes mellitus (T2DM). Our investigation explored the changes in the normal microbiome that occur upon high-fat diet feeding and how dietary Dendrobium officinale polysaccharides (DOP) can benefit the treatment of T2DM by mitigating gut microbial dysbiosis. In addition, we have evaluated the changes in lipid metabolism in T2DM mice. Results suggest that HFD feeding (8 weeks) and streptozotocin (120 mg/kg b.w) result in insulin resistance, hyperlipidemia, and gut microbial dysbiosis associated with T2DM. Treatment with DOP results in improved glucose and insulin tolerance, as well as a better plasma and tissue lipid profile. In addition, histopathological and molecular changes support the biochemical observations. Results of gut microbiome studies based on 16S rRNA sequencing suggest that DOP plays a role in improving the population of beneficial bacterial species. In summary, DOP attenuated hyperlipidemia by regulating gut microbial dysbiosis in T2DM.
Riferimenti bibliografici
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Douglas G.M., Maffei V.J., Zaneveld J.R., Yurgel S.N., Brown J.R., Taylor C.M., Huttenhower C., Langille M.G.I. PICRUSt2 for prediction of metagenome functions. Nat. Biotechnol. 2020, 38(6), 685–688. 10.1038/s41587-020-0548-6
Du Vigneaud V., Karr W.G. Carbohydrates utilization rate of disappearance of d-glucose from the blood. J. Biol. Chem. 1925, 66, 281–300.
Edgar R.C. UPARSE: Highly accurate OTU sequences from microbial amplicon reads. Nat. Methods. 2013, 10(10), 996–998. 10.1038/nmeth.2604
Folch J., Lees M., Sloane Stanley G.H. A simple method for the isolation and purification of total lipids from animal tissues. J. Biol. Chem. 1957, 226(1), 497–509.
Galicia-Garcia U., Benito-Vicente A., Jebari S., Larrea-Sebal A., et al. Pathophysiology of type 2 diabetes mellitus. Int. J. Mol. Sci. 2020, 21, 6275. 10.3390/ijms21176275
Gevers D., Kugathasan S., Denson L.A., Vázquez-Baeza Y., Van Treuren W., Ren B., Schwager E., Knights D., Song S.J., Yassour M., et al. The treatment-naive microbiome in new-onset Crohn’s disease. Cell Host Microbe. 2014, 15(3), 382–392. 10.1016/j.chom.2014.02.005
Hung W.C., Hung W.W., Tsai H.J., Chang C.C., et al. The association of targeted gut microbiota with body composition in type 2 diabetes mellitus. Int. J. Med. Sci. 2021, 18, 511–519. 10.7150/ijms.51164
Jandhyala S.M., Madhulika A., Deepika G., Rao G.V., et al. Altered intestinal microbiota in patients with chronic pancreatitis: Implications in diabetes and metabolic abnormalities. Sci. Rep. 2017, 7, 43640. 10.1038/srep43640.
Jayachandran M., Christudas S., Zheng X., Xu B. Dietary fiber konjac glucomannan exerts an antidiabetic effect via inhibiting lipid absorption and regulation of PPAR-γ and gut microbiome. Food Chem. 2023, 403, 134336. 10.1016/j.foodchem.2022.134336
Jayachandran M., Wu Z., Ganesan K., Khalid S., Chung S.M., Xu B. Isoquercetin upregulates antioxidant genes, suppresses inflammatory cytokines, and regulates the AMPK pathway in streptozotocin-induced diabetic rats. Chem. Biol. Interact. 2019, 303, 62–69. 10.1016/j.cbi.2019.02.017
Jayachandran M., Zhang T., Wu Z., Liu Y., Xu B. Isoquercetin regulates SREBP-1C via the AMPK pathway in skeletal muscle to exert antihyperlipidemic and anti-inflammatory effects in STZ-induced diabetic rats. Mol. Biol. Rep. 2020, 47, 593–602. 10.1007/s11033-019-05166-y
Jia L., Li W., Li J., Li Y., et al. Lycium barbarum polysaccharide attenuates high-fat diet-induced hepatic steatosis by up-regulating SIRT1 expression and deacetylase activity. Sci. Rep. 2016, 6, 36209. 10.1038/srep36209
Jia X., Xu W., Zhang L., Li X., et al. Impact of gut microbiota and microbiota-related metabolites on hyperlipidemia. Front. Cell. Infect. Microbiol. 2021, 11, 634780. 10.3389/fcimb.2021.634780
Kheriji N., Dakhlaoui T., Kamoun Rebai W., Maatoug S., et al. Prevalence and risk factors of diabetes mellitus and hypertension in North East Tunisia calling for efficient and effective actions. Sci. Rep. 2023, 13, 12706. 10.1038/s41598-023-39197-0
Khoshnejat M., Kavousi K., Banaei-Moghaddam A.M., Moosavi-Movahedi A.A. Unraveling the molecular heterogeneity in type 2 diabetes: A potential subtype discovery followed by metabolic modeling. BMC Med. Genomics 2020, 13, 119. 10.1186/s12920-020-00767-0
Lei L., Zhao N., Zhang L., Chen J., Liu X., Piao S. Gut microbiota is a potential goalkeeper of dyslipidemia. Front. Endocrinol. 2022, 13, 950826. 10.3389/fendo.2022.950826
Li L., Yao H., Li X., Zhang Q., et al. Destiny of Dendrobium officinale polysaccharide after oral administration: Indigestible and nonabsorbing, ends in modulating gut microbiota. J. Agric. Food Chem. 2019, 67, 5968–5977. 10.1021/acs.jafc.9b01489
Li X., Jayachandran M., Xu B. Antidiabetic effect of konjac glucomannan via insulin signaling pathway regulation in high-fat diet and streptozotocin-induced diabetic rats. Food Res. Int. 2021, 149, 110664. 10.1016/j.foodres.2021.110664
Liu C., Zhao D., Ma W., Guo Y., et al. Denitrifying sulfide removal process on high-salinity wastewaters in the presence of Halomonas sp. Appl. Microbiol. Biotechnol. 2016, 100, 1421–1426.
Liu H., Xing Y., Wang Y., Ren X., et al. Dendrobium officinale polysaccharide prevents diabetes via the regulation of gut microbiota in prediabetic mice. Foods 2023, 12, 2310. 10.3390/foods12122310
Liu Y., Yang L., Zhang Y., Liu X., et al. Dendrobium officinale polysaccharide ameliorates diabetic hepatic glucose metabolism via glucagon-mediated signaling pathways and modifying liver-glycogen structure. J. Ethnopharmacol. 2020, 248, 112308. 10.1016/j.jep.2019.112308
Ma Y., Sun Y., Sun L., Liu X., et al. Effects of gut microbiota and fatty acid metabolism on dyslipidemia following weight-loss diets in women: Results from a randomized controlled trial. Clin. Nutr. 2021, 40, 5511–5520. 10.1016/j.clnu.2021.09.021
Magoc T., Salzberg S.L. FLASH: Fast length adjustment of short reads to improve genome assemblies. Bioinformatics. 2011, 27(21), 2957–2963. 10.1093/bioinformatics/btr507
Quast C., Pruesse E., Yilmaz P., Gerken J., Schweer T., Yarza P., Peplies J., Glöckner F.O. The SILVA ribosomal RNA gene database project: Improved data processing and web-based tools. Nucleic Acids Res. 2013, 41(D1), D590–D596. 10.1093/nar/gks1219
Ruze R., Liu T., Zou X., Song J., et al. Obesity and type 2 diabetes mellitus: Connections in epidemiology, pathogenesis, and treatments. Front. Endocrinol. 2023, 14, 1161521. 10.3389/fendo.2023.1161521
Schloss P.D., Westcott S.L., Ryabin T., Hall J.R., Hartmann M., Hollister E.B., Lesniewski R.A., Oakley B.B., Parks D.H., Robinson C.J., et al. Introducing mothur: Open-source, platform-independent, community-supported software for describing and comparing microbial communities. Appl. Environ. Microbiol. 2009, 75(23), 7537–7541. 10.1128/AEM.01541-09
Shetty S.S., Kumari S. Fatty acids and their role in type-2 diabetes (Review). Exp. Ther. Med. 2021, 22, 706. 10.3892/etm.2021.10138
Sun H., Saeedi P., Karuranga S., Pinkepank M., Ogurtsova K., et al. Erratum to “IDF diabetes atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045” [Diabetes Res. Clin. Pract. 183 (2022) 109119]. Diabetes Res. Clin. Pract. 2023, 204, 110945. 10.1016/j.diabres.2023.110945
Vourakis M., Mayer G., Rousseau G. The role of gut microbiota on cholesterol metabolism in atherosclerosis. Int. J. Mol. Sci. 2021, 22, 8074. 10.3390/ijms22158074
Wang P., Liu Y., Zhang T., Yin C., et al. Effects of root extract of Morinda officinalis in mice with high-fat-diet/streptozotocin-induced diabetes and C2C12 myoblast differentiation. ACS Omega 2021, 6, 26959–26968.
Wang Q., Garrity G.M., Tiedje J.M., Cole J.R. Naive Bayesian classifier for rapid assignment of rRNA sequences into the new bacterial taxonomy. Appl. Environ. Microbiol. 2007, 73(16), 5261–5267. 10.1128/AEM.00062-07
Wondmkun Y.T. Obesity, Insulin resistance, and type 2 diabetes: Associations and therapeutic implications. Diabetes Metab. Syndr. Obes. Targets Ther. 2020, 13, 3611–3616. 10.2147/DMSO.S275898
Wu W., Zhao Z., Zhang D., et al. Structure, health benefits, mechanisms, and gut microbiota of Dendrobium officinale polysaccharides: A review. Nutrients 2023, 15, 4901. 10.3390/nu15234901
Xu X., Zhang C., Wang N., Xu Y., Tang G., Xu L., Feng Y. Bioactivities and mechanism of actions of dendrobium officinale: A comprehensive Review. Oxid. Med. Cell. Longev. 2022, 2022, 6293355. 10.1155/2022/6293355
Zhao Y., Jayachandran M., Xu B. In vivo antioxidant and anti-inflammatory effects of soluble dietary fiber Konjac glucomannan in type-2 diabetic rats. Int. J. Biol. Macromol. 2020, 159, 1186–1196. 10.1016/j.ijbiomac.2020.05.105
Zhou X., Lian P., Liu H., Wang Y., Zhou M., Feng Z. Causal associations between gut microbiota and different types of dyslipidemia: A two-sample mendelian randomization study. Nutrients 2023, 15, 4445. 10.3390/nu15204445
Zhou Z., Sun B., Yu D., Zhu C. Gut microbiota: An important player in type 2 diabetes mellitus. Front. Cell. Infect. Microbiol. 2022, 12, 834485. 10.3389/fcimb.2022.834485
Chen S., Zhou Y., Chen Y., Gu J. Fastp: An ultra-fast all-in-one FASTQ preprocessor. Bioinformatics. 2018, 34(17), i884–i890. 10.1093/bioinformatics/bty560
Chong K., Chang J.K., Chuang L.M. Recent advances in the treatment of type 2 diabetes mellitus using new drug therapies. Kaohsiung J. Med. Sci. 2024, 40, 212–220. 10.1002/kjm2.12800
Cunningham A.L., Stephens J.W., Harris D.A. Gut microbiota influence in type 2 diabetes mellitus (T2DM). Gut Pathog. 2021, 13, 50. 10.1186/s13099-021-00446-0
Dhananjayan R., Koundinya K.S., Malati T., Kutala V.K. Endothelial dysfunction in type 2 diabetes mellitus. Indian J. Clin. Biochem. 2016, 31, 372–379. 10.1007/s12291-015-0516-y
Dludla P.V., Mabhida S.E., Ziqubu K., Nkambule B.B., Mazibuko-Mbeje S.E., Hanser S., Basson A.K., Pheiffer C., Kengne A.P. Pancreatic β-cell dysfunction in type 2 diabetes: Implications of inflammation and oxidative stress. World J. Diab. 2023, 14, 130–146. 10.4239/wjd.v14.i3.130
Douglas G.M., Maffei V.J., Zaneveld J.R., Yurgel S.N., Brown J.R., Taylor C.M., Huttenhower C., Langille M.G.I. PICRUSt2 for prediction of metagenome functions. Nat. Biotechnol. 2020, 38(6), 685–688. 10.1038/s41587-020-0548-6
Du Vigneaud V., Karr W.G. Carbohydrates utilization rate of disappearance of d-glucose from the blood. J. Biol. Chem. 1925, 66, 281–300.
Edgar R.C. UPARSE: Highly accurate OTU sequences from microbial amplicon reads. Nat. Methods. 2013, 10(10), 996–998. 10.1038/nmeth.2604
Folch J., Lees M., Sloane Stanley G.H. A simple method for the isolation and purification of total lipids from animal tissues. J. Biol. Chem. 1957, 226(1), 497–509.
Galicia-Garcia U., Benito-Vicente A., Jebari S., Larrea-Sebal A., et al. Pathophysiology of type 2 diabetes mellitus. Int. J. Mol. Sci. 2020, 21, 6275. 10.3390/ijms21176275
Gevers D., Kugathasan S., Denson L.A., Vázquez-Baeza Y., Van Treuren W., Ren B., Schwager E., Knights D., Song S.J., Yassour M., et al. The treatment-naive microbiome in new-onset Crohn’s disease. Cell Host Microbe. 2014, 15(3), 382–392. 10.1016/j.chom.2014.02.005
Hung W.C., Hung W.W., Tsai H.J., Chang C.C., et al. The association of targeted gut microbiota with body composition in type 2 diabetes mellitus. Int. J. Med. Sci. 2021, 18, 511–519. 10.7150/ijms.51164
Jandhyala S.M., Madhulika A., Deepika G., Rao G.V., et al. Altered intestinal microbiota in patients with chronic pancreatitis: Implications in diabetes and metabolic abnormalities. Sci. Rep. 2017, 7, 43640. 10.1038/srep43640.
Jayachandran M., Christudas S., Zheng X., Xu B. Dietary fiber konjac glucomannan exerts an antidiabetic effect via inhibiting lipid absorption and regulation of PPAR-γ and gut microbiome. Food Chem. 2023, 403, 134336. 10.1016/j.foodchem.2022.134336
Jayachandran M., Wu Z., Ganesan K., Khalid S., Chung S.M., Xu B. Isoquercetin upregulates antioxidant genes, suppresses inflammatory cytokines, and regulates the AMPK pathway in streptozotocin-induced diabetic rats. Chem. Biol. Interact. 2019, 303, 62–69. 10.1016/j.cbi.2019.02.017
Jayachandran M., Zhang T., Wu Z., Liu Y., Xu B. Isoquercetin regulates SREBP-1C via the AMPK pathway in skeletal muscle to exert antihyperlipidemic and anti-inflammatory effects in STZ-induced diabetic rats. Mol. Biol. Rep. 2020, 47, 593–602. 10.1007/s11033-019-05166-y
Jia L., Li W., Li J., Li Y., et al. Lycium barbarum polysaccharide attenuates high-fat diet-induced hepatic steatosis by up-regulating SIRT1 expression and deacetylase activity. Sci. Rep. 2016, 6, 36209. 10.1038/srep36209
Jia X., Xu W., Zhang L., Li X., et al. Impact of gut microbiota and microbiota-related metabolites on hyperlipidemia. Front. Cell. Infect. Microbiol. 2021, 11, 634780. 10.3389/fcimb.2021.634780
Kheriji N., Dakhlaoui T., Kamoun Rebai W., Maatoug S., et al. Prevalence and risk factors of diabetes mellitus and hypertension in North East Tunisia calling for efficient and effective actions. Sci. Rep. 2023, 13, 12706. 10.1038/s41598-023-39197-0
Khoshnejat M., Kavousi K., Banaei-Moghaddam A.M., Moosavi-Movahedi A.A. Unraveling the molecular heterogeneity in type 2 diabetes: A potential subtype discovery followed by metabolic modeling. BMC Med. Genomics 2020, 13, 119. 10.1186/s12920-020-00767-0
Lei L., Zhao N., Zhang L., Chen J., Liu X., Piao S. Gut microbiota is a potential goalkeeper of dyslipidemia. Front. Endocrinol. 2022, 13, 950826. 10.3389/fendo.2022.950826
Li L., Yao H., Li X., Zhang Q., et al. Destiny of Dendrobium officinale polysaccharide after oral administration: Indigestible and nonabsorbing, ends in modulating gut microbiota. J. Agric. Food Chem. 2019, 67, 5968–5977. 10.1021/acs.jafc.9b01489
Li X., Jayachandran M., Xu B. Antidiabetic effect of konjac glucomannan via insulin signaling pathway regulation in high-fat diet and streptozotocin-induced diabetic rats. Food Res. Int. 2021, 149, 110664. 10.1016/j.foodres.2021.110664
Liu C., Zhao D., Ma W., Guo Y., et al. Denitrifying sulfide removal process on high-salinity wastewaters in the presence of Halomonas sp. Appl. Microbiol. Biotechnol. 2016, 100, 1421–1426.
Liu H., Xing Y., Wang Y., Ren X., et al. Dendrobium officinale polysaccharide prevents diabetes via the regulation of gut microbiota in prediabetic mice. Foods 2023, 12, 2310. 10.3390/foods12122310
Liu Y., Yang L., Zhang Y., Liu X., et al. Dendrobium officinale polysaccharide ameliorates diabetic hepatic glucose metabolism via glucagon-mediated signaling pathways and modifying liver-glycogen structure. J. Ethnopharmacol. 2020, 248, 112308. 10.1016/j.jep.2019.112308
Ma Y., Sun Y., Sun L., Liu X., et al. Effects of gut microbiota and fatty acid metabolism on dyslipidemia following weight-loss diets in women: Results from a randomized controlled trial. Clin. Nutr. 2021, 40, 5511–5520. 10.1016/j.clnu.2021.09.021
Magoc T., Salzberg S.L. FLASH: Fast length adjustment of short reads to improve genome assemblies. Bioinformatics. 2011, 27(21), 2957–2963. 10.1093/bioinformatics/btr507
Quast C., Pruesse E., Yilmaz P., Gerken J., Schweer T., Yarza P., Peplies J., Glöckner F.O. The SILVA ribosomal RNA gene database project: Improved data processing and web-based tools. Nucleic Acids Res. 2013, 41(D1), D590–D596. 10.1093/nar/gks1219
Ruze R., Liu T., Zou X., Song J., et al. Obesity and type 2 diabetes mellitus: Connections in epidemiology, pathogenesis, and treatments. Front. Endocrinol. 2023, 14, 1161521. 10.3389/fendo.2023.1161521
Schloss P.D., Westcott S.L., Ryabin T., Hall J.R., Hartmann M., Hollister E.B., Lesniewski R.A., Oakley B.B., Parks D.H., Robinson C.J., et al. Introducing mothur: Open-source, platform-independent, community-supported software for describing and comparing microbial communities. Appl. Environ. Microbiol. 2009, 75(23), 7537–7541. 10.1128/AEM.01541-09
Shetty S.S., Kumari S. Fatty acids and their role in type-2 diabetes (Review). Exp. Ther. Med. 2021, 22, 706. 10.3892/etm.2021.10138
Sun H., Saeedi P., Karuranga S., Pinkepank M., Ogurtsova K., et al. Erratum to “IDF diabetes atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045” [Diabetes Res. Clin. Pract. 183 (2022) 109119]. Diabetes Res. Clin. Pract. 2023, 204, 110945. 10.1016/j.diabres.2023.110945
Vourakis M., Mayer G., Rousseau G. The role of gut microbiota on cholesterol metabolism in atherosclerosis. Int. J. Mol. Sci. 2021, 22, 8074. 10.3390/ijms22158074
Wang P., Liu Y., Zhang T., Yin C., et al. Effects of root extract of Morinda officinalis in mice with high-fat-diet/streptozotocin-induced diabetes and C2C12 myoblast differentiation. ACS Omega 2021, 6, 26959–26968.
Wang Q., Garrity G.M., Tiedje J.M., Cole J.R. Naive Bayesian classifier for rapid assignment of rRNA sequences into the new bacterial taxonomy. Appl. Environ. Microbiol. 2007, 73(16), 5261–5267. 10.1128/AEM.00062-07
Wondmkun Y.T. Obesity, Insulin resistance, and type 2 diabetes: Associations and therapeutic implications. Diabetes Metab. Syndr. Obes. Targets Ther. 2020, 13, 3611–3616. 10.2147/DMSO.S275898
Wu W., Zhao Z., Zhang D., et al. Structure, health benefits, mechanisms, and gut microbiota of Dendrobium officinale polysaccharides: A review. Nutrients 2023, 15, 4901. 10.3390/nu15234901
Xu X., Zhang C., Wang N., Xu Y., Tang G., Xu L., Feng Y. Bioactivities and mechanism of actions of dendrobium officinale: A comprehensive Review. Oxid. Med. Cell. Longev. 2022, 2022, 6293355. 10.1155/2022/6293355
Zhao Y., Jayachandran M., Xu B. In vivo antioxidant and anti-inflammatory effects of soluble dietary fiber Konjac glucomannan in type-2 diabetic rats. Int. J. Biol. Macromol. 2020, 159, 1186–1196. 10.1016/j.ijbiomac.2020.05.105
Zhou X., Lian P., Liu H., Wang Y., Zhou M., Feng Z. Causal associations between gut microbiota and different types of dyslipidemia: A two-sample mendelian randomization study. Nutrients 2023, 15, 4445. 10.3390/nu15204445
Zhou Z., Sun B., Yu D., Zhu C. Gut microbiota: An important player in type 2 diabetes mellitus. Front. Cell. Infect. Microbiol. 2022, 12, 834485. 10.3389/fcimb.2022.834485
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Jan 1, 2026
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Jayachandran, M., Liu, J., & Qu, S. (2026). The interplay between Dendrobium Officinale polysaccharide, gut microbiota, and lipid metabolism in HFD/STZ-induced type 2 diabetic mice. Italian Journal of Food Science, 38(1), 22-34. https://doi.org/10.15586/ijfs.v38i1.3104
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Come citare
Jayachandran, M., Liu, J., & Qu, S. (2026). The interplay between Dendrobium Officinale polysaccharide, gut microbiota, and lipid metabolism in HFD/STZ-induced type 2 diabetic mice. Italian Journal of Food Science, 38(1), 22-34. https://doi.org/10.15586/ijfs.v38i1.3104