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ORIGINAL RESEARCH ARTICLE

Gut microbiome dysbiosis and colorectal cancer in low- and middle-income countries and the United States: A comparative analysis

Vaishnavi Chilakamarri1 ,  Roshan Paudel1*
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1 Department of Computer Science, School of Computer, Mathematical and Natural Sciences Morgan State University, Baltimore, Maryland , United States of America
MI, 026320095 https://doi.org/10.36922/MI026320095
Received: 4 August 2026 | Revised: 3 October 2026 | Accepted: 12 October 2026 | Published online: 26 October 2026
© 2026 by the Author(3). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Colorectal cancer (CRC) is a major cause of cancer deaths globally, with rising cases in low- and middle-income countries (LMICs). These trends have been associated with socioeconomic and lifestyle changes accompanying urbanization and dietary Westernization. The gut microbiome has emerged as a key mediator linking environmental factors to CRC. Microbial dysbiosis has been associated with a myriad of downstream carcinogenic effects through metabolic, immune, and inflammatory pathways. However, most existing research on microbiome-related CRC risk focuses on Western populations, creating a gap in comparative characterization of CRC-associated microbiomes in LMIC populations. To fill this gap, the study analyzed publicly available 16S ribosomal RNA (rRNA) sequencing datasets from Sri Lanka, Kenya, and the United States. We performed analyses in R and Python, including taxonomic profiling and alpha- and beta-diversity assessments. The results showed a consistently higher relative abundance of Fusobacteria in CRC than in controls across all populations (8.19% vs 1.64%). Alpha diversity analysis showed slightly higher microbial diversity in controls than in CRC samples, although Wilcoxon tests found no significant within-population differences, while Kruskal–Wallis and Dunn’s tests identified significant population-level differences. Among CRC samples, United States (U.S.) cohorts exhibited the highest median Shannon diversity, followed by Kenya and Sri Lanka. Beta diversity showed substantial overlap among the U.S. cohorts, whereas Sri Lankan and Kenyan samples showed greater dispersion, indicating more variability. However, significant differences in multivariate dispersion (permutational analysis of multivariate dispersion, p = 0.006) indicated that differences in within-group heterogeneity also contributed to the observed separation. These findings highlight substantial microbial variability observed across populations, consistent with environment and lifestyle changes previously reported in transitioning populations. This research addresses a gap in the comparative characterization of CRC-associated microbiomes in underprivileged LMICs and provides a basis for future research evaluating environmental, dietary, and clinical factors.

Graphical abstract
Keywords
Colorectal cancer
Gut microbiome
16S ribosomal RNA
Microbial diversity
Fusobacteria
Low- and middle-income countries
Funding
None.
Conflict of interest
The authors have no conflicts of interest to declare.
References
  1. Brenner H, Chen C. The colorectal cancer epidemic: challenges and opportunities for primary, secondary and tertiary prevention. Br J Cancer. 2018;119(7):785-792. doi: 10.1038/s41416-018-0264-x
  2. Siegel RL, Wagle NS, Star J, Kratzer TB, Smith RA, Jemal A. Colorectal cancer statistics, 2026. CA Cancer J Clin. 2026;76(2). doi: 10.3322/caac.70067
  3. Yang G, Yu X, Weisenberger DJ, Lu T, Liang G. A multi-omics overview of colorectal cancer to address mechanisms of disease, metastasis, patient disparities and outcomes. Cancers. 2023;15(11):2934. doi: 10.3390/cancers15112934
  4. Cherry LM. The Genetic Etiology of Familial and Nonfamilial Colorectal Cancer. Bayl Univ Med Cent Proc. 2011;24(2):139-141. doi: 10.1080/08998280.2011.11928702
  5. Maddula M, Cohen J, Kumarasinghe D, et al. Risk Factors in Sporadic Early-Onset Colorectal Cancer, Current Evidence and Emerging Insights: A Systematic Review. Cancers. 2026;18(10):1515. doi: 10.3390/cancers18101515
  6. Merie G, Al-hashimi H. The Role of Pathogenic Mutations in Colorectal Cancer. Int J Pathol Biomark. 2025;1(1):12-31. doi: 10.71428/IJPB.2025.0102
  7. Sung H, Filho AM, Laversanne M, et al. Global cancer statistics 2024: GLOBOCAN estimates of incidence and mortality worldwide for 34 cancers in 186 countries. CA A Cancer J Clin. 2026;76(4):e70090. doi: 10.3322/caac.70090
  8. Keenan J, Waddell O, McCombie A, et al. Risk Factors for Early-Onset Colorectal Cancer: The Role of Diet, Lifestyle and Obesity. Res Sq. Preprint posted online November 5, 2025. doi: 10.21203/rs.3.rs-7707153/v1
  9. Bishehsari F, Mahdavinia M, Vacca M, Malekzadeh R, Mariani-Costantini R. Epidemiological transition of colorectal cancer in developing countries: environmental factors, molecular pathways, and opportunities for prevention. World J Gastroenterol. 2014;20(20):6055. doi: 10.3748/wjg.v20.i20.6055
  10. Owolo O. Urbanization-Induced Gut Microbiome Dysbiosis and Type 2 Diabetes in Sub-Saharan Africa: A Systematic Review of Mechanisms and Indigenous Therapeutics. Preprints.org. 2026. doi: 10.20944/preprints202601.1838.v1
  11. Ramaboli MC, Ocvirk S, Khan Mirzaei M, et al. Diet changes due to urbanization in South Africa are linked to microbiome and metabolome signatures of Westernization and colorectal cancer. Nat Commun. 2024;15(1):3379. doi: 10.1038/s41467-024-46265-0
  12. Huang P, Wong CC. Microbiome in Colorectal Cancer. In: Yu J, ed. Microbiome in Gastrointestinal Cancer. Singapore: Springer Nature; 2023:23-39. doi: 10.1007/978-981-19-4492-5_3
  13. Yadav D, Sainatham C, Filippov E, Kanagala SG, Ishaq SM, Jayakrishnan T. Gut microbiome–colorectal cancer relationship. Microorganisms. 2024;12(3):484. doi: 10.3390/microorganisms12030484
  14. Coleman OI, Haller D. Dysbiosis of the intestinal microbiota and colorectal cancer. In: Colorectal Neoplasia and the Colorectal Microbiome. Academic Press; 2020:135-155. doi: 10.1016/B978-0-12-819672-4.00007-6
  15. Kosumi K, Mima K, Baba H, Ogino S. Dysbiosis of the gut microbiota and colorectal cancer: the key target of molecular pathological epidemiology. J Lab Precis Med. 2018;3:76. doi: 10.21037/jlpm.2018.09.05
  16. Alexander JL, Scott AJ, Pouncey AL, Marchesi J, Kinross J, Teare J. Colorectal carcinogenesis: An archetype of gut microbiota–host interaction. ecancermedicalscience. 2018;12:865. doi: 10.3332/ecancer.2018.865
  17. Bultman SJ. Interplay between diet, gut microbiota, epigenetic events, and colorectal cancer. Mol Nutr Food Res. 2017;61(1):1500902. doi: 10.1002/mnfr.201500902
  18. David LA, Maurice CF, Carmody RN, et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2014;505(7484):559-563. doi: 10.1038/nature12820
  19. Ou J, Carbonero F, Zoetendal EG, et al. Diet, microbiota, and microbial metabolites in colon cancer risk in rural Africans and African Americans. Am J Clin Nutr. 2013;98(1):111-120. doi: 10.3945/ajcn.112.056689
  20. Vipperla K, O’Keefe SJ. Diet, microbiota, and dysbiosis: a ‘recipe’ for colorectal cancer. Food Funct. 2016;7(4):1731-1740. doi: 10.1039/c5fo01276g
  21. Paulo LS, Msema Bwire G, Klipstein-Grobusch K, et al. Urbanization gradient, diet, and gut microbiota in Sub-Saharan Africa: a systematic review. Front Microbiomes. 2023;2:1208166. doi: 10.3389/frmbi.2023.1208166
  22. Tamburini FB, Maghini D, Oduaran OH, et al. Short-and long-read metagenomics of urban and rural South African gut microbiomes reveal a transitional composition and undescribed taxa. Nat Commun. 2022;13(1):926. doi: 10.1038/s41467-021-27917-x
  23. Nayak SP, Sasi MP, Sreejayan MP, Mandal S. A case-control study of roles of diet in colorectal carcinoma in a South Indian Population. Asian Pac J Cancer Prev. 2009;10(4):565-568. Accessed February 19 2026. https://pubmed.ncbi.nlm.nih.gov/19827870/
  24. Young C, Wood HM, Seshadri RA, et al. The colorectal cancer-associated faecal microbiome of developing countries resembles that of developed countries. Genome Med. 2021;13(1):27. doi: 10.1186/s13073-021-00844-8
  25. Katsidzira L, Ocvirk S, Wilson A, et al. Differences in Fecal Gut Microbiota, Short-Chain Fatty Acids and Bile Acids Link Colorectal Cancer Risk to Dietary Changes Associated with Urbanization Among Zimbabweans. Nutr Cancer. 2019;71(8):1313-1324. doi: 10.1080/01635581.2019.1602659
  26. Lee DJ, Parikh A, Sirohi B, Cao Y, Chan AT. Emerging trends in the global burden of colorectal cancer. Nat Rev Clin Oncol. 2026;23(8):569-581. doi: 10.1038/s41571-026-01149-8
  27. Gamage BD, Ranasinghe D, Sahankumari A, Malavige GN. Metagenomic analysis of colonic tissue and stool microbiome in patients with colorectal cancer in a South Asian population. BMC Cancer. 2024;24(1):1124. doi: 10.1186/s12885-024-12885-4
  28. Elkholy A, Avuthu N, Abdalla M, et al. Microbiome diversity in African American, European American, and Egyptian colorectal cancer patients. Heliyon. 2023;9(7). doi: 10.1016/j.heliyon.2023.e18035
  29. Obuya S, Elkholy A, Avuthu N, et al. A signature of Prevotella copri and Faecalibacterium prausnitzii depletion, and a link with bacterial glutamate degradation in the Kenyan colorectal cancer patients. J Gastrointest Oncol. 2022;13(5):2282-2292. doi: 10.21037/jgo-22-116
  30. Callahan BJ, McMurdie PJ, Rosen MJ, Han AW, Johnson AJA, Holmes SP. DADA2: High-resolution sample inference from Illumina amplicon data. Nat Methods. 2016;13(7):581-583. doi: 10.1038/nmeth.3869
  31. Shannon CE. A mathematical theory of communication. Bell Syst Tech J. 1948;27(3):379-423. doi: 10.1002/j.1538-7305.1948.tb01338.x
  32. Simpson EH. Measurement of diversity. Nature. 1949;163(4148):688. doi: 10.1038/163688a0
  33. Bray JR, Curtis JT. An ordination of the upland forest communities of southern Wisconsin. Ecol Monogr. 1957;27(4):325-349. doi: 10.2307/1942268
  34. Avuthu N, Guda C. Meta-Analysis of Altered Gut Microbiota Reveals Microbial and Metabolic Biomarkers for Colorectal Cancer. Microbiol Spectr. 2022;10(4). doi: 10.1128/spectrum.00013-22
  35. Zeller G, Tap J, Voigt AY, et al. Potential of fecal microbiota for early-stage detection of colorectal cancer. Mol Syst Biol. 2014;10(11):766. doi: 10.15252/msb.20145645
  36. Thakur BK, Choudhury SR, Turpin W, Martin A. Gut microbiota and diet in colorectal cancer: Converging determinants of carcinogenesis. Gut Microbes. 2026;18(1). doi: 10.1080/19490976.2026.2664684
  37. Mntambo N, Arumugam T, Pramchand A, Pillay K, Ramsuran V. A review of global patterns in gut microbiota composition, health and disease: locating South Africa in the conversation. Microorganisms. 2025;13(12):2831. doi: 10.3390/microorganisms13122831
  38. Datorre JG, de Carvalho AC, Guimaraes DP, Reis RM. The role of Fusobacterium nucleatum in colorectal carcinogenesis. Pathobiology. 2021;88(2):127-140. doi: 10.1159/000512175
  39. Hill CM, Malen RC, Reedy AM, et al. Associations of epidemiologic risk factors with Fusobacterium nucleatum and bacterial alpha diversity in the colorectal tumor-associated microbiota. Cancer Causes Control. 2026;37(3):45. doi: 10.1007/s10552-026-02133-4
  40. Ou S, Wang H, Tao Y, et al. Fusobacterium nucleatum and colorectal cancer: From phenomenon to mechanism. Front Cell Infect Microbiol. 2022;12:1020583. doi: 10.3389/fcimb.2022.1020583
  41. Lu W, Aihaiti A, Abudukeranmu P, Liu Y, Gao H. Unravelling the role of intratumoral bacteria in digestive system cancers: current insights and future perspectives. J Transl Med. 2024;22(1):545. doi: 10.1186/s12967-024-05320-6
  42. Darnindro N, Abdullah M, Sukartini N, et al. Differences in diversity and composition of mucosa-associated colonic microbiota in colorectal cancer and non-colorectal cancer in Indonesia. World J Gastroenterol. 2025;31(7):100051. doi: 10.3748/wjg.v31.i7.100051
  43. Wirbel J, Pyl PT, Kartal E, et al. Meta-analysis of fecal metagenomes reveals global microbial signatures that are specific for colorectal cancer. Nat Med. 2019;25(4):679-689. doi: 10.1038/s41591-019-0406-6
  44. Thomas AM, Manghi P, Asnicar F, et al. Metagenomic analysis of colorectal cancer datasets identifies cross-cohort microbial diagnostic signatures and a link with choline degradation. Nat Med. 2019;25(4):667-678. doi: 10.1038/s41591-019-0405-7
  45. Shi J, Shen H, Huang H, et al. Gut microbiota characteristics of colorectal cancer patients in Hubei, China, and differences with cohorts from other Chinese regions. Front Microbiol. 2024;15:1395514. doi: 10.3389/fmicb.2024.1395514
  46. Ma J, Kim N, Cha JH, et al. A human gut metagenome-assembled genome catalogue spanning 41 countries supports genome-scale metabolic models. Nat Microbiol. 2026;11(1):317-334. doi: 10.1038/s41564-025-02206-1
  47. Gérard P. The crosstalk between the gut microbiota and lipids. OCL Oilseeds Fats Crops Lipids. 2020;27(12):70. doi: 10.1051/ocl/2020070
  48. Kong F, Cai Y. Study Insights into Gastrointestinal Cancer through the Gut Microbiota. Biomed Res Int. 2019;2019:1-8. doi: 10.1155/2019/8721503
  49. O’Keefe SJ, Chung D, Mahmoud N, et al. Why do African Americans get more colon cancer than Native Africans? J Nutr. 2007;137(1):175S-182S. doi: 10.1093/jn/137.1.175S
  50. Sharma S, O’Keefe SJ. Environmental influences on the high mortality from colorectal cancer in African Americans. Postgrad Med J. 2007;83(983):583-589. doi: 10.1136/pgmj.2007.058958
  51. Pardamean CI, Sudigyo D, Budiarto A, et al. Changing Colorectal Cancer Trends in Asians: Epidemiology and Risk Factors. Oncol Rev. 2023;17:10576. doi: 10.3389/or.2023.10576
  52. Weerasekara PC, Withanachchi CR, Ginigaddara GAS, Ploeger A. Nutrition transition and traditional food cultural changes in Sri Lanka during colonization and post-colonization. Foods. 2018;7(7):111. doi: 10.3390/foods7070111
  53. Vásquez A, Zúñiga P, Torres K, Quest AF, Simón L. Beneficial effects of a high-anthocyanin diet versus a Westernized diet on colorectal cancer risk: a systematic review. Front Immunol. 2026;17:1736018. doi: 10.3389/fimmu.2026.1736018
  54. Osswald A, Wortmann E, Wylensek D, et al. Secondary bile acid production by gut bacteria promotes Western diet-associated colorectal cancer. Gut. 2026;75(8):1505-1519. doi: 10.1136/gutjnl-2024-332243
  55. Kase BE, Liese AD, Zhang J, Murphy EA, Steck SE. Association Between the Dietary Index for Gut Microbiota (DI-GM) and Colorectal Cancer in the PLCO Cohort. Nutrients. 2026;18(7):1088. doi: 10.3390/nu18071088
  56. Rosendal LB, Bundgaard C, Zhang J, et al. Adherence to the EAT-Lancet diet and risk of colorectal cancer in the general population and among individuals with diabetes: a cohort study. Eur J Nutr. 2026;65(3):90. doi: 10.1007/s00394-026-03936-6
  57. Aykan NF. Red meat and colorectal cancer. Oncol Rev. 2015;9:288. doi: 10.4081/oncol.2015.288
  58. Zhou Z, Kleis L, Depetris-Chauvin A, et al. Beneficial microbiome and diet interplay in early-onset colorectal cancer. EMBO Mol Med. 2025;17(1):9-30. doi: 10.1038/s44321-024-00177-0
  59. Smolińska K, Paluszkiewicz P. Risk of colorectal cancer in relation to frequency and total amount of red meat consumption. Systematic review and meta-analysis. Arch Med Sci. 2010;6(4):605-610. doi: 10.5114/aoms.2010.14475
  60. Farvid MS, Sidahmed E, Spence ND, Mante Angua K, Rosner BA, Barnett JB. Consumption of red meat and processed meat and cancer incidence: a systematic review and meta-analysis of prospective studies. Eur J Epidemiol. 2021;36(9):937-951. doi: 10.1007/s10654-021-00741-9
  61. Cheung HS, Lu LY, So WL, Wong HW, Wong SH, Mak CM. Association of Red Meat Intake and Colorectal Cancer among East-Asians: A Systematic Review and Meta-analysis of Observational Studies Performed between 2011-2021. J Gastrointestin Liver Dis. 2023;32(3):377. doi: 10.15403/jgld-4778
  62. Iswarya SK, Premarajan KC, Kar SS, Kumar SS, Kate V. Risk factors for the development of colorectal carcinoma: A case control study from South India. World J Gastrointest Oncol. 2016;8(2):207. doi: 10.4251/wjgo.v8.i2.207
  63. Kotemori A, Kito K, Iwasaki M, et al. Dietary Inflammatory Index and Risk of Colorectal Cancer in Japanese Men. Nutrients. 2026;18(2):338. doi: 10.3390/nu18020338
  64. Ganesh B, Talole SD, Dikshit R. A case–control study on diet and colorectal cancer from Mumbai, India. Cancer Epidemiol. 2009;33(3-4):189-193. doi: 10.1016/j.canep.2009.07.009
  65. Maiyoh GK, Tuei VC. Rising Cancer Incidence and Role of the Evolving Diet in Kenya. Nutr Cancer. 2019;71(4):531-546. doi: 10.1080/01635581.2018.1542010
  66. Ramachandran SL, Pasupuleti N, Abdill RJ, et al. Distinct trajectories of urbanization shape the human gut microbiome across South Asia. Gut Microbes. 2026;18(1). doi: 10.1080/19490976.2026.2700042
  67. Huang Z, Li Y, Park H, et al. Unveiling and harnessing the human gut microbiome in the rising burden of non-communicable diseases during urbanization. Gut Microbes. 2023;15(1):2237645. doi: 10.1080/19490976.2023.2237645
  68. Hassan M, Butt ZA. Applying the syndemic framework to cancer research for effective cancer control in low- and middle-income countries. ecancermedicalscience. 2023;17:1532. doi: 10.3332/ecancer.2023.1532
  69. Moyo G, Nyanhanda T, Mude W, et al. Diet and Cancers of the Gastrointestinal Tract in Africa: A Systematic Review and Meta-Analysis. Soc Sci Res Netw. 2025. doi: 10.2139/ssrn.5317670
  70. Abo-Hammam RH, Salah M, Shabayek S, Hanora A, Zakeer S, Khattab RH. Metagenomic analysis of fecal samples in colorectal cancer Egyptians patients post colectomy: a pilot study. AIMS Microbiol. 2024;10(1):148. doi: 10.3934/microbiol.2024008
  71. Siraj YA, Biadgelign MG, Yassin MO, Chekol YZ. Mucosa‐associated cultivable aerobic gut bacterial microbiota among colorectal cancer patients attending at the referral hospitals of Amhara Regional State, Ethiopia. Gut Pathog. 2021;13(1):19. doi: 10.1186/s13099-021-00415-7
  72. Pu T, Gustafson A, Ghabra S, et al. Underrepresentation of racial and ethnic minorities in metastatic colorectal carcinoma clinical trials within the United States. Ann Oncol. 2023;34(suppl 1). doi: 10.1016/j.annonc.2023.04.188
  73. Pham YTH, Jin A, Wang R, Koh WP, Yuan JM, Luu HN. Association between dietary one-carbon metabolism-related nutrients and the risk of colorectal cancer: Findings from the Singapore Chinese Health Study. Cancer Res. 2023;83(7 suppl):6449-6449. doi: 10.1158/1538-7445.AM2023-6449
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