Early-stage Hyperglycemia-induced Gut Microbial Changes Are Partially Associated with Mechanical Allodynia in <i>db/db</i> Mice

Xinting Wang; Jihong Wu; Simin Qi; Rui Huang; Xiaoping Wu; Lin Tian; Peili Wang; Shenglan Wang

doi:doi:10.11648/j.ijde.20210604.15

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Early-stage Hyperglycemia-induced Gut Microbial Changes Are Partially Associated with Mechanical Allodynia in db/db Mice

Xinting Wang, Jihong Wu, Simin Qi, Rui Huang, Xiaoping Wu, Lin Tian, Peili Wang, Shenglan Wang

Published in International Journal of Diabetes and Endocrinology (Volume 6, Issue 4)

Received: 27 October 2021 Accepted: 22 November 2021 Published: 2 December 2021

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Abstract

Recent studies have demonstrated that pain is partially regulated by the gut microbiota. However, the association of gut microbiota with painful diabetic neuropathy, a common complication of diabetes, remains unclear. Herein, we investigated whether the gut microbiota is associated with mechanical allodynia during the early stage of hyperglycemia in 7-week-old db/db mice. The db/db mice were intraperitoneally injected with metformin for 2 weeks. Using the von Frey test and gut microbiota analyses, we investigated the association of gut microbial changes with mechanical allodynia in 7-week-old mice. In db/db mice, colonic microbial community profiles were altered, and both unweighted and weighted UniFrac distances were reduced. Colonic genus-level abundances of Alloprevotella and Prevotellaceae_UCG-001 were positively correlated with mechanical allodynia in db/db mice, while the abundance of Odoribacter was negatively correlated. Intraperitoneal injection of metformin for 2 weeks alleviated mechanical allodynia in db/db mice but did not achieve an anti-diabetic effect. Metformin altered colonic microbial communities and increased weighted UniFrac distance in db/db mice, although its analgesic effect was not associated with specific bacteria. Additionally, alteration of small intestinal microbial community profiles and reduction in weighted UniFrac distance were observed in db/db mice, which were not affected by metformin. These results provide potential evidence of the association of the gut microbiota with mechanical allodynia during early-stage of hyperglycemia.

Published in	International Journal of Diabetes and Endocrinology (Volume 6, Issue 4)
DOI	10.11648/j.ijde.20210604.15
Page(s)	150-159
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

Gut Microbiota, Painful Diabetic Neuropathy, Mechanical Allodynia, Metformin

References

[1]	Santoni, M., F. Miccini, and N. Battelli. (2021). Gut microbiota, immunity and pain. Immunol Lett, 229: p. 44-47.
[2]	Guo, R., L. H. Chen, C. Xing, and T. Liu. (2019). Pain regulation by gut microbiota: molecular mechanisms and therapeutic potential. Br J Anaesth, 123 (5): p. 637-654.
[3]	Luczynski, P., M. Tramullas, M. Viola, F. Shanahan, G. Clarke, S. O'Mahony, et al. (2017). Microbiota regulates visceral pain in the mouse. Elife, 6.
[4]	O'Mahony, S. M., V. D. Felice, K. Nally, H. M. Savignac, M. J. Claesson, P. Scully, et al. (2014). Disturbance of the gut microbiota in early-life selectively affects visceral pain in adulthood without impacting cognitive or anxiety-related behaviors in male rats. Neuroscience, 277: p. 885-901.
[5]	Verdu, E. F., P. Bercik, M. Verma-Gandhu, X. X. Huang, P. Blennerhassett, W. Jackson, et al. (2006). Specific probiotic therapy attenuates antibiotic induced visceral hypersensitivity in mice. Gut, 55 (2): p. 182-90.
[6]	Shen, S., G. Lim, Z. You, W. Ding, P. Huang, C. Ran, et al. (2017). Gut microbiota is critical for the induction of chemotherapy-induced pain. Nat Neurosci, 20 (9): p. 1213-1216.
[7]	Amaral, F. A., D. Sachs, V. V. Costa, C. T. Fagundes, D. Cisalpino, T. M. Cunha, et al. (2008). Commensal microbiota is fundamental for the development of inflammatory pain. Proc Natl Acad Sci U S A, 105 (6): p. 2193-7.
[8]	Yang, C., X. Fang, G. Zhan, N. Huang, S. Li, J. Bi, et al. (2019). Key role of gut microbiota in anhedonia-like phenotype in rodents with neuropathic pain. Transl Psychiatry, 9 (1): p. 57.
[9]	Guastella, V. and G. Mick. (2009). Strategies for the diagnosis and treatment of neuropathic pain secondary to diabetic peripheral sensory polyneuropathy. Diabetes Metab, 35 (1): p. 12-9.
[10]	Boulton, A. J., R. A. Malik, J. C. Arezzo, and J. M. Sosenko. (2004). Diabetic somatic neuropathies. Diabetes Care, 27 (6): p. 1458-86.
[11]	Malik, R. A. (2020). Diabetic neuropathy: A focus on small fibres. Diabetes Metab Res Rev, 36 Suppl 1: p. e3255.
[12]	Scholz, J., J. P. Rathmell, W. S. David, D. A. Chad, A. C. Broderick, S. G. Perros, et al. (2016). A standardized clinical evaluation of phenotypic diversity in diabetic polyneuropathy. Pain, 157 (10): p. 2297-2308.
[13]	Wang, S., K. Kobayashi, Y. Kogure, H. Yamanaka, S. Yamamoto, H. Yagi, et al. (2018). Negative Regulation of TRPA1 by AMPK in Primary Sensory Neurons as a Potential Mechanism of Painful Diabetic Neuropathy. Diabetes, 67 (1): p. 98-109.
[14]	Iqbal, Z., S. Azmi, R. Yadav, M. Ferdousi, M. Kumar, D. J. Cuthbertson, et al. (2018). Diabetic Peripheral Neuropathy: Epidemiology, Diagnosis, and Pharmacotherapy. Clin Ther, 40 (6): p. 828-849.
[15]	Vallianou, N. G., T. Stratigou, and S. Tsagarakis. (2019). Metformin and gut microbiota: their interactions and their impact on diabetes. Hormones (Athens), 18 (2): p. 141-144.
[16]	Forslund, K., F. Hildebrand, T. Nielsen, G. Falony, E. Le Chatelier, S. Sunagawa, et al. (2015). Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota. Nature, 528 (7581): p. 262-266.
[17]	Gurung, M., Z. Li, H. You, R. Rodrigues, D. B. Jump, A. Morgun, et al. (2020). Role of gut microbiota in type 2 diabetes pathophysiology. EBioMedicine, 51: p. 102590.
[18]	Wu, H., E. Esteve, V. Tremaroli, M. T. Khan, R. Caesar, L. Mannerås-Holm, et al. (2017). Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug. Nat Med, 23 (7): p. 850-858.
[19]	Fugmann, M., M. Breier, M. Rottenkolber, F. Banning, U. Ferrari, V. Sacco, et al. (2015). The stool microbiota of insulin resistant women with recent gestational diabetes, a high risk group for type 2 diabetes. Sci Rep, 5: p. 13212.
[20]	Yuan, Y., J. Zhou, Y. Zheng, Z. Xu, Y. Li, S. Zhou, et al. (2020). Beneficial effects of polysaccharide-rich extracts from Apocynum venetum leaves on hypoglycemic and gut microbiota in type 2 diabetic mice. Biomed Pharmacother, 127: p. 110182.
[21]	Kang, Y., Y. Li, Y. Du, L. Guo, M. Chen, X. Huang, et al. (2019). Konjaku flour reduces obesity in mice by modulating the composition of the gut microbiota. Int J Obes (Lond), 43 (8): p. 1631-1643.
[22]	Wei, S., R. Han, J. Zhao, S. Wang, M. Huang, Y. Wang, et al. (2018). Intermittent administration of a fasting-mimicking diet intervenes in diabetes progression, restores beta cells and reconstructs gut microbiota in mice. Nutr Metab (Lond), 15: p. 80.
[23]	Li, H., F. Liu, J. Lu, J. Shi, J. Guan, F. Yan, et al. (2020). Probiotic Mixture of Lactobacillus plantarum Strains Improves Lipid Metabolism and Gut Microbiota Structure in High Fat Diet-Fed Mice. Front Microbiol, 11: p. 512.
[24]	Duan, C., L. Kuang, X. Xiang, J. Zhang, Y. Zhu, Y. Wu, et al. (2020). Activated Drp1-mediated mitochondrial ROS influence the gut microbiome and intestinal barrier after hemorrhagic shock. Aging (Albany NY), 12 (2): p. 1397-1416.
[25]	Song, X., L. Zhong, N. Lyu, F. Liu, B. Li, Y. Hao, et al. (2019). Inulin Can Alleviate Metabolism Disorders in ob/ob Mice by Partially Restoring Leptin-related Pathways Mediated by Gut Microbiota. Genomics Proteomics Bioinformatics, 17 (1): p. 64-75.
[26]	Lin, B., Y. Wang, P. Zhang, Y. Yuan, Y. Zhang, and G. Chen. (2020). Gut microbiota regulates neuropathic pain: potential mechanisms and therapeutic strategy. J Headache Pain, 21 (1): p. 103.
[27]	Zhou, F., X. Wang, B. Han, X. Tang, R. Liu, Q. Ji, et al. (2021). Short-chain fatty acids contribute to neuropathic pain via regulating microglia activation and polarization. Mol Pain, 17: p. 1744806921996520.
[28]	Wang, S., S. Qi, Y. Kogure, H. Kanda, L. Tian, S. Yamamoto, et al. (2020). The ubiquitin E3 ligase Nedd 4-2 relieves mechanical allodynia through the ubiquitination of TRPA1 channel in db/db mice. Eur J Neurosci.
[29]	Tseng, C. H. (2018). Metformin and Helicobacter pylori Infection in Patients With Type 2 Diabetes. Diabetes Care, 41 (4): p. e42-e43.
[30]	Shin, N. R., J. C. Lee, H. Y. Lee, M. S. Kim, T. W. Whon, M. S. Lee, et al. (2014). An increase in the Akkermansia spp. population induced by metformin treatment improves glucose homeostasis in diet-induced obese mice. Gut, 63 (5): p. 727-35.
[31]	Silamiķele, L., I. Silamiķelis, M. Ustinova, Z. Kalniņa, I. Elbere, R. Petrovska, et al. (2021). Metformin Strongly Affects Gut Microbiome Composition in High-Fat Diet-Induced Type 2 Diabetes Mouse Model of Both Sexes. Frontiers in Endocrinology, 12 (231).
[32]	Hannachi, N. and L. Camoin-Jau. (2021). Drug Response Diversity: A Hidden Bacterium? J Pers Med, 11 (5).
[33]	Schalliol, L. A. and J. M. Pittman, Chapter 35 - Insulin and other hypoglycemic drugs, in Side Effects of Drugs Annual, S. D. Ray, Editor. 2020, Elsevier. p. 441-448.
[34]	Lee, H., Y. Lee, J. Kim, J. An, S. Lee, H. Kong, et al. (2018). Modulation of the gut microbiota by metformin improves metabolic profiles in aged obese mice. Gut Microbes, 9 (2): p. 155-165.
[35]	Zhang, X., Y. Zhao, J. Xu, Z. Xue, M. Zhang, X. Pang, et al. (2015). Modulation of gut microbiota by berberine and metformin during the treatment of high-fat diet-induced obesity in rats. Scientific Reports, 5 (1): p. 14405.
[36]	Louis, S., R. M. Tappu, A. Damms-Machado, D. H. Huson, and S. C. Bischoff. (2016). Characterization of the Gut Microbial Community of Obese Patients Following a Weight-Loss Intervention Using Whole Metagenome Shotgun Sequencing. PLoS One, 11 (2): p. e0149564.
[37]	Dong, T. S., H. H. Chang, M. Hauer, V. Lagishetty, W. Katzka, E. Rozengurt, et al. (2019). Metformin alters the duodenal microbiome and decreases the incidence of pancreatic ductal adenocarcinoma promoted by diet-induced obesity. Am J Physiol Gastrointest Liver Physiol, 317 (6): p. G763-g772.
[38]	Duca, F. A., T. M. Z. Waise, W. T. Peppler, and T. K. T. Lam. (2021). The metabolic impact of small intestinal nutrient sensing. Nat Commun, 12 (1): p. 903.
[39]	Bauer, P. V., F. A. Duca, T. M. Z. Waise, B. A. Rasmussen, M. A. Abraham, H. J. Dranse, et al. (2018). Metformin Alters Upper Small Intestinal Microbiota that Impact a Glucose-SGLT1-Sensing Glucoregulatory Pathway. Cell Metab, 27 (1): p. 101-117. e5.

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APA Style

Xinting Wang, Jihong Wu, Simin Qi, Rui Huang, Xiaoping Wu, et al. (2021). Early-stage Hyperglycemia-induced Gut Microbial Changes Are Partially Associated with Mechanical Allodynia in db/db Mice. International Journal of Diabetes and Endocrinology, 6(4), 150-159. https://doi.org/10.11648/j.ijde.20210604.15

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ACS Style

Xinting Wang; Jihong Wu; Simin Qi; Rui Huang; Xiaoping Wu, et al. Early-stage Hyperglycemia-induced Gut Microbial Changes Are Partially Associated with Mechanical Allodynia in db/db Mice. Int. J. Diabetes Endocrinol. 2021, 6(4), 150-159. doi: 10.11648/j.ijde.20210604.15

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AMA Style

Xinting Wang, Jihong Wu, Simin Qi, Rui Huang, Xiaoping Wu, et al. Early-stage Hyperglycemia-induced Gut Microbial Changes Are Partially Associated with Mechanical Allodynia in db/db Mice. Int J Diabetes Endocrinol. 2021;6(4):150-159. doi: 10.11648/j.ijde.20210604.15

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@article{10.11648/j.ijde.20210604.15,
  author = {Xinting Wang and Jihong Wu and Simin Qi and Rui Huang and Xiaoping Wu and Lin Tian and Peili Wang and Shenglan Wang},
  title = {Early-stage Hyperglycemia-induced Gut Microbial Changes Are Partially Associated with Mechanical Allodynia in db/db Mice},
  journal = {International Journal of Diabetes and Endocrinology},
  volume = {6},
  number = {4},
  pages = {150-159},
  doi = {10.11648/j.ijde.20210604.15},
  url = {https://doi.org/10.11648/j.ijde.20210604.15},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ijde.20210604.15},
  abstract = {Recent studies have demonstrated that pain is partially regulated by the gut microbiota. However, the association of gut microbiota with painful diabetic neuropathy, a common complication of diabetes, remains unclear. Herein, we investigated whether the gut microbiota is associated with mechanical allodynia during the early stage of hyperglycemia in 7-week-old db/db mice. The db/db mice were intraperitoneally injected with metformin for 2 weeks. Using the von Frey test and gut microbiota analyses, we investigated the association of gut microbial changes with mechanical allodynia in 7-week-old mice. In db/db mice, colonic microbial community profiles were altered, and both unweighted and weighted UniFrac distances were reduced. Colonic genus-level abundances of Alloprevotella and Prevotellaceae_UCG-001 were positively correlated with mechanical allodynia in db/db mice, while the abundance of Odoribacter was negatively correlated. Intraperitoneal injection of metformin for 2 weeks alleviated mechanical allodynia in db/db mice but did not achieve an anti-diabetic effect. Metformin altered colonic microbial communities and increased weighted UniFrac distance in db/db mice, although its analgesic effect was not associated with specific bacteria. Additionally, alteration of small intestinal microbial community profiles and reduction in weighted UniFrac distance were observed in db/db mice, which were not affected by metformin. These results provide potential evidence of the association of the gut microbiota with mechanical allodynia during early-stage of hyperglycemia.},
 year = {2021}
}

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TY  - JOUR
T1  - Early-stage Hyperglycemia-induced Gut Microbial Changes Are Partially Associated with Mechanical Allodynia in db/db Mice
AU  - Xinting Wang
AU  - Jihong Wu
AU  - Simin Qi
AU  - Rui Huang
AU  - Xiaoping Wu
AU  - Lin Tian
AU  - Peili Wang
AU  - Shenglan Wang
Y1  - 2021/12/02
PY  - 2021
N1  - https://doi.org/10.11648/j.ijde.20210604.15
DO  - 10.11648/j.ijde.20210604.15
T2  - International Journal of Diabetes and Endocrinology
JF  - International Journal of Diabetes and Endocrinology
JO  - International Journal of Diabetes and Endocrinology
SP  - 150
EP  - 159
PB  - Science Publishing Group
SN  - 2640-1371
UR  - https://doi.org/10.11648/j.ijde.20210604.15
AB  - Recent studies have demonstrated that pain is partially regulated by the gut microbiota. However, the association of gut microbiota with painful diabetic neuropathy, a common complication of diabetes, remains unclear. Herein, we investigated whether the gut microbiota is associated with mechanical allodynia during the early stage of hyperglycemia in 7-week-old db/db mice. The db/db mice were intraperitoneally injected with metformin for 2 weeks. Using the von Frey test and gut microbiota analyses, we investigated the association of gut microbial changes with mechanical allodynia in 7-week-old mice. In db/db mice, colonic microbial community profiles were altered, and both unweighted and weighted UniFrac distances were reduced. Colonic genus-level abundances of Alloprevotella and Prevotellaceae_UCG-001 were positively correlated with mechanical allodynia in db/db mice, while the abundance of Odoribacter was negatively correlated. Intraperitoneal injection of metformin for 2 weeks alleviated mechanical allodynia in db/db mice but did not achieve an anti-diabetic effect. Metformin altered colonic microbial communities and increased weighted UniFrac distance in db/db mice, although its analgesic effect was not associated with specific bacteria. Additionally, alteration of small intestinal microbial community profiles and reduction in weighted UniFrac distance were observed in db/db mice, which were not affected by metformin. These results provide potential evidence of the association of the gut microbiota with mechanical allodynia during early-stage of hyperglycemia.
VL  - 6
IS  - 4
ER  -

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Author Information

Xinting Wang

School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, China
Jihong Wu

School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, China
Simin Qi

School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, China
Rui Huang

School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, China
Xiaoping Wu

National Clinical Research Center for Chinese Medicine Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
Lin Tian

Department of Gerontology, Guang'anmen Hospital, China Academy of Chinese Medical Science, Beijing, China
Peili Wang

National Clinical Research Center for Chinese Medicine Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
Shenglan Wang

School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, China

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Xinting Wang, Jihong Wu, Simin Qi, Rui Huang, Xiaoping Wu, et al. (2021). Early-stage Hyperglycemia-induced Gut Microbial Changes Are Partially Associated with Mechanical Allodynia in db/db Mice. International Journal of Diabetes and Endocrinology, 6(4), 150-159. https://doi.org/10.11648/j.ijde.20210604.15

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ACS Style

Xinting Wang; Jihong Wu; Simin Qi; Rui Huang; Xiaoping Wu, et al. Early-stage Hyperglycemia-induced Gut Microbial Changes Are Partially Associated with Mechanical Allodynia in db/db Mice. Int. J. Diabetes Endocrinol. 2021, 6(4), 150-159. doi: 10.11648/j.ijde.20210604.15

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AMA Style

Xinting Wang, Jihong Wu, Simin Qi, Rui Huang, Xiaoping Wu, et al. Early-stage Hyperglycemia-induced Gut Microbial Changes Are Partially Associated with Mechanical Allodynia in db/db Mice. Int J Diabetes Endocrinol. 2021;6(4):150-159. doi: 10.11648/j.ijde.20210604.15

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@article{10.11648/j.ijde.20210604.15,
  author = {Xinting Wang and Jihong Wu and Simin Qi and Rui Huang and Xiaoping Wu and Lin Tian and Peili Wang and Shenglan Wang},
  title = {Early-stage Hyperglycemia-induced Gut Microbial Changes Are Partially Associated with Mechanical Allodynia in db/db Mice},
  journal = {International Journal of Diabetes and Endocrinology},
  volume = {6},
  number = {4},
  pages = {150-159},
  doi = {10.11648/j.ijde.20210604.15},
  url = {https://doi.org/10.11648/j.ijde.20210604.15},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ijde.20210604.15},
  abstract = {Recent studies have demonstrated that pain is partially regulated by the gut microbiota. However, the association of gut microbiota with painful diabetic neuropathy, a common complication of diabetes, remains unclear. Herein, we investigated whether the gut microbiota is associated with mechanical allodynia during the early stage of hyperglycemia in 7-week-old db/db mice. The db/db mice were intraperitoneally injected with metformin for 2 weeks. Using the von Frey test and gut microbiota analyses, we investigated the association of gut microbial changes with mechanical allodynia in 7-week-old mice. In db/db mice, colonic microbial community profiles were altered, and both unweighted and weighted UniFrac distances were reduced. Colonic genus-level abundances of Alloprevotella and Prevotellaceae_UCG-001 were positively correlated with mechanical allodynia in db/db mice, while the abundance of Odoribacter was negatively correlated. Intraperitoneal injection of metformin for 2 weeks alleviated mechanical allodynia in db/db mice but did not achieve an anti-diabetic effect. Metformin altered colonic microbial communities and increased weighted UniFrac distance in db/db mice, although its analgesic effect was not associated with specific bacteria. Additionally, alteration of small intestinal microbial community profiles and reduction in weighted UniFrac distance were observed in db/db mice, which were not affected by metformin. These results provide potential evidence of the association of the gut microbiota with mechanical allodynia during early-stage of hyperglycemia.},
 year = {2021}
}

Copy | Download

TY  - JOUR
T1  - Early-stage Hyperglycemia-induced Gut Microbial Changes Are Partially Associated with Mechanical Allodynia in db/db Mice
AU  - Xinting Wang
AU  - Jihong Wu
AU  - Simin Qi
AU  - Rui Huang
AU  - Xiaoping Wu
AU  - Lin Tian
AU  - Peili Wang
AU  - Shenglan Wang
Y1  - 2021/12/02
PY  - 2021
N1  - https://doi.org/10.11648/j.ijde.20210604.15
DO  - 10.11648/j.ijde.20210604.15
T2  - International Journal of Diabetes and Endocrinology
JF  - International Journal of Diabetes and Endocrinology
JO  - International Journal of Diabetes and Endocrinology
SP  - 150
EP  - 159
PB  - Science Publishing Group
SN  - 2640-1371
UR  - https://doi.org/10.11648/j.ijde.20210604.15
AB  - Recent studies have demonstrated that pain is partially regulated by the gut microbiota. However, the association of gut microbiota with painful diabetic neuropathy, a common complication of diabetes, remains unclear. Herein, we investigated whether the gut microbiota is associated with mechanical allodynia during the early stage of hyperglycemia in 7-week-old db/db mice. The db/db mice were intraperitoneally injected with metformin for 2 weeks. Using the von Frey test and gut microbiota analyses, we investigated the association of gut microbial changes with mechanical allodynia in 7-week-old mice. In db/db mice, colonic microbial community profiles were altered, and both unweighted and weighted UniFrac distances were reduced. Colonic genus-level abundances of Alloprevotella and Prevotellaceae_UCG-001 were positively correlated with mechanical allodynia in db/db mice, while the abundance of Odoribacter was negatively correlated. Intraperitoneal injection of metformin for 2 weeks alleviated mechanical allodynia in db/db mice but did not achieve an anti-diabetic effect. Metformin altered colonic microbial communities and increased weighted UniFrac distance in db/db mice, although its analgesic effect was not associated with specific bacteria. Additionally, alteration of small intestinal microbial community profiles and reduction in weighted UniFrac distance were observed in db/db mice, which were not affected by metformin. These results provide potential evidence of the association of the gut microbiota with mechanical allodynia during early-stage of hyperglycemia.
VL  - 6
IS  - 4
ER  -

Copy | Download