Gut Microbiota Alterations, Biochemical Markers, and Dietary Patterns in Type 2 Diabetes Mellitus: A Cross-Sectional Study in Sokoto, Nigeria

Asiya Umar Imam; Muhammad Lawal Jidda; Jafaru Muhammad Bunza; Bilkisu Mainasara Mika`ilu; Nura Muhammad Bunza; Halimatu Husaini Salisu; Wali Usman; Nasiru Suleiman; Muhammad Kabiru Dallatu

doi:10.31149/ijimm.v4i9.2999

Authors

Asiya Umar Imam Department of Medical Microbiology, School of Medical Laboratory Sciences, Usmanu Danfodiyo University, Sokoto, Nigeria
Muhammad Lawal Jidda Department of Chemical Pathology, School of Medical Laboratory Sciences, Usmanu Danfodiyo University, Sokoto, Nigeria
Jafaru Muhammad Bunza Department of Chemical Pathology, School of Medical Laboratory Sciences, Usmanu Danfodiyo University, Sokoto, Nigeria
Bilkisu Mainasara Mika`ilu Department of Medical Microbiology, School of Medical Laboratory Sciences, Usmanu Danfodiyo University, Sokoto, Nigeria
Nura Muhammad Bunza Department of Medical Laboratory Sciences, Faculty of Allied Health Sciences, Bayero University, Kano Nigeria
Halimatu Husaini Salisu Department of Chemical Pathology, School of Medical Laboratory Sciences, Usmanu Danfodiyo University, Sokoto, Nigeria
Wali Usman Department of Chemical Pathology, School of Medical Laboratory Sciences, Usmanu Danfodiyo University, Sokoto, Nigeria
Nasiru Suleiman Department of Veterinary Physiology and Biochemistry, Faculty of Veterinary Medicine, Usmanu Danfodiyo University, Sokoto, Nigeria. Centre for Advanced Medical Research and Training, Usmanu Danfodiyo University, Sokoto, Nigeria
Muhammad Kabiru Dallatu Department of Chemical Pathology, School of Medical Laboratory Sciences, Usmanu Danfodiyo University, Sokoto, Nigeria

DOI:

https://doi.org/10.31149/ijimm.v4i9.2999

Keywords:

Type 2 diabetes mellitus, gut dysbiosis, Firmicutes/Bacteroidetes ratio, TNF-α, TMAO, branched-chain amino acids, fecal calprotectin, dietary patterns, Nigeria

Abstract

Background: Type 2 diabetes mellitus (T2DM) is increasingly linked to gut microbiota dysbiosis, yet the relationship between microbial alterations, specific biochemical markers, and dietary patterns remains underexplored in African populations. This study examined associations between gut microbiota composition, circulating pro-inflammatory cytokines, fecal calprotectin, and dietary patterns in T2DM patients in Sokoto, Nigeria. Methods: A cross-sectional study enrolled 126 participants (63 T2DM patients and 63 age- and sex-matched healthy controls). We quantified gut microbiota (Bacteroidetes and Firmicutes) using qPCR. We measured plasma levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), as well as fecal calprotectin, using ELISA. We assessed dietary patterns using a structured questionnaire. We assessed associations between microbial abundance and biomarkers using Spearman's correlation, and analyzed clinical/dietary factors associated with dysbiosis using chi-square tests and logistic regression. Results: Among T2DM patients, 51 (81.0%) exhibited gut dysbiosis, characterized by an elevated Firmicutes/Bacteroidetes (F/B) ratio. Participants with dysbiosis had significantly higher median concentrations of TNF-α (41.41 ng/L), IL-6 (2.34 pg/mL), and fecal calprotectin (47.05 pg/mL) than controls (p < 0.05 for all). Hyperglycemia showed the strongest association with dysbiosis (χ² = 107.47, p < 0.001). Dietary analysis showed that rice/swallow consumption at breakfast was associated with 83.3% dysbiosis prevalence (χ² = 13.321, p = 0.038), while 100% of participants who consumed oats at dinner had dysbiosis (χ² = 53.784, p < 0.001). In dysbiotic patients, the F/B ratio correlated strongly with TNF-α (r = 0.782, p = 0.001), moderately with IL-6 (r = 0.352, p = 0.032) and faecal calprotectin (r = -0.530, p = 0.001). We observed no significant correlations in the eubiotic or control groups. Conclusion: Gut dysbiosis in T2DM is associated with elevated systemic inflammation, altered microbial metabolites, intestinal inflammation, and specific dietary patterns. These findings support the gut–systemic inflammatory axis and highlight the potential for microbiome-targeted dietary interventions in T2DM management, particularly in resource-limited settings.

References

[1] American Diabetes Association. Classification and diagnosis of diabetes: Standards of medical care in diabetes—2022. Diabetes Care. 2022;45(Supplement 1):S17–S38.

[2] International Diabetes Federation. IDF Diabetes Atlas. 11th ed. Brussels: International Diabetes Federation; 2021.

[3] Arora A, Behl T, Sehgal A, et al. Unraveling the involvement of gut microbiota in type 2 diabetes mellitus. Life Sci. 2021;273:119311.

[4] Ezenabor EH, Adeyemi AA, Adeyemi OS. Gut microbiota and metabolic syndrome: Relationships and opportunities for new therapeutic strategies. Best Pract Res Clin Gastroenterol. 2024;72:101892.

[5] Knudsen JK, Leutscher P, Sørensen S. Gut microbiota in bone health and diabetes. Curr Osteoporos Rep. 2021;19(4):462–479.

[6] Gurung M, Li Z, You H, et al. Role of gut microbiota in type 2 diabetes pathophysiology. EBioMedicine. 2020;51:102590.

[7] Cani PD, Van Hul M, Lefort C. Gut microbiota and metabolic endotoxemia in type 2 diabetes. Nat Rev Endocrinol. 2023;19(5):305–317.

[8] Młynarska E, Wasiak J, Gajewska A, et al. Exploring the significance of gut microbiota in diabetes pathogenesis and management: A narrative review. Nutrients. 2024;16:1938.

[9] Rohm TV, Meier DT, Donath MY. Toll-like receptors in metabolic disease and therapeutic targeting. Nat Rev Endocrinol. 2022;18(12):712–724.

[10] Amar J, Chabo C, Waget A. Metabolic endotoxemia: A trigger for obesity-related inflammation? Nat Rev Endocrinol. 2022;18(2):123–136.

[11] Tang WHW, Backhed F, Landmesser U, Hazen SL. Gut microbiota in cardiovascular health and disease. Nat Rev Cardiol. 2022;19(5):325–337.

[12] Kong L, Zhao Q, Jiang X, et al. Trimethylamine N-oxide impairs β-cell function and glucose tolerance. Nat Commun. 2024;15(1):2526.

[13] White PJ, McGarrah RW, Grimsrud PA, et al. The BCKDH kinase and phosphatase integrate BCAA and lipid metabolism via regulation of ATP-citrate lyase. Cell Metab. 2021;33(1):200–217.

[14] Zhang L, Li H. The gut microbiota-branched-chain amino acid axis in metabolic disease: From correlation to causation. Annu Rev Nutr. 2024;44:327–350.

[15] Sun Y, Liu B, Zhang X. Elevated fecal calprotectin levels are associated with type 2 diabetes mellitus and correlated with glycemic control. Diabetes Res Clin Pract. 2022;188:109936.

[16] Guo X, Xia X, Tang R, et al. Development of a real-time PCR method for Firmicutes and Bacteroidetes in feces and its application to quantify intestinal population of obese and lean pigs. Lett Appl Microbiol. 2008;47(5):367–373.

[17] Castaner O, Goday A, Park YM, et al. The gut microbiome profile in obesity: A systematic review. Int J Endocrinol. 2022;2022:4096372.

[18] Wang Y, Dilidaxi D, Wu Y. Dysbiosis of gut microbiota in type 2 diabetes: A systematic review and meta-analysis. Gut. 2022;71(3):534–543.

[19] Magne F, Gotteland M, Gauthier L, et al. The Firmicutes/Bacteroidetes ratio: A relevant marker of gut dysbiosis in obese patients? Nutrients. 2020;12(5):1474.

[20] Adamu H, Inuwa H, Taura MG, Bilbis LS. Levels of inflammatory cytokines and lipid profile in obese type 2 diabetic patients in Sokoto, Nigeria. Sub-Saharan Afr J Med. 2021;8(2):67–73.

[21] Falony G, Vandeputte D, Raes J. The microbiome in health and disease: A new era of human microbial ecology. Lancet Gastroenterol Hepatol. 2022;7(1):56–68.

[22] Pedersen HK, Forslund SK, Gudmundsdottir V, et al. A metagenome-wide association study of the gut microbiome and serum metabolome in type 2 diabetes reveals functional pathways for branched-chain amino acid biosynthesis. Nat Commun. 2023;14(1):5051.

[23] Allin KH, Tremaroli V, Caesar R, et al. Aberrant intestinal microbiota in individuals with prediabetes. Diabetologia. 2021;64(4):834–845.

[24] Stefan N. Metabolically healthy and unhealthy normal weight and obesity. Endocrinol Metab. 2020;35(3):487–493.

[25] Kim HN, Jeon SG. Methodological considerations for human microbiome studies in association with disease. Gut Liver. 2022;16(5):665–672.

[26] Jidda ML, Bunza JM, Salihu HH, et al. Plasma branched-chain amino acids are associated with gut dysbiosis and inflammatory markers in type 2 diabetes mellitus. Adv Gut Microbiome Res. 2026;2026:9295759.

[27] Adebamowo SN, Adeyemo AA, Rotimi CN. Gut microbiota and diabetes in African populations: A systematic review. Nat Rev Endocrinol. 2023;19(8):456–470.

[28] Owolabi MO, Arulogun O, Melikam S, et al. The burden of non-communicable diseases in Nigeria: A systematic review. Glob Heart. 2023;18(1):12.