Back to basic – dietary microbial modulation for colorectal cancer prevention – for Hong Kong Chinese

CRC incidence and impact

Colorectal cancer [CRC] is one of the most common malignancies worldwide [1]. According to Globocan 2018, there were 18 million newly diagnosed cancer cases worldwide, while CRC made up 10.2%, topped the third highest cancer incidence. In the same year, CRC had the second highest mortality rate with more than 880,000 lives lost to it [2]. The environmental and heritable factors of colorectal cancer [CRC] is around 35% [3]. Up to 3%-5% of all CRC are represented by the hereditary syndromes [4]. Meanwhile, a higher incidence of CRC is observed in more developed regions than under developed regions, and changes in lifestyle and dietary habits are believed to attribute to an increased incidence [1,5]. In Hong Kong, CRC has been the most common cancer since 2013 [6], with more than 5,000 new diagnoses annually, accounts for 50.8% male, 31.5% female with an upward trend in 2017 [7]. The dietary habits of people in Hong Kong have steered away from the traditional Chinese diet, to fast-pace dining comprised of processed food and reduced diversity. Although the association between microbiota and the risk of CRC is indistinct, the undoubted fact is that CRC patients have less diverse microbiota than their healthy counter parts [8]. In this commentary, we would like to discuss the potential benefits of resuming a traditional diet which is relatively similar to the Mediterranean diet to modulate microbial risk in CRC in Hong Kong Chinese.

Microbial risk in developing CRC

Most microbial species in the gastrointestinal tract belong to Firmicutes, Bacteroidetes, Proteobacteria and Actinobacteria. Gut microbiota has a highly complex ecosystem composed of thousands of species and strains [9] which interacts with one another, the substrates, and the host that form a microbial-diet-host interaction. CRC risk may be determined through microbial profile with recent evidence showing that altered microbiome environment, or dysbiosis, in the gut and pathogenic bacterial colonies overgrowth has implication in cancer development [10-12]. Some gut microbiomes are even identified, known as CRC microbial markers, to promote colorectal tumorigenesis [12,13]. Certain unfavorable bacteria namely Fusobacterium nucleatum, Escherichia coli, Bacteroides fragilis, Clostridium hathewayi, and Bacteroides clarus are identified to be more abundant in CRC patients [14-18], while the beneficial bacteria are reduced [19]. Moreover, dysbiosis is observed in patients with CRC, among a cluster of chronic diseases, i.e. inflammatory bowel disease, diabetes mellitus, obesity [20-22]. The commonality amongst the diseases is chronic inflammation, which is critical factor in the development of CRC [23]. Some microbiomes induce inflammation via lipopolysaccharides [LPS], while the others are correlated with elevated serum C-Reactive Protein [CRP] [24-27]. Despite whether the shift in microbiota was a result of disease development, the abnormality in its composition has been implicated as a potentially important etiological factor in the initiation and progression of CRC [28] that diet is undeniably a key player.

Westernization is a global phenomenon

Hong Kong has a long history of westernization since her colonial era began in the 19th century, but many Chinese Hong Kong residents retained a traditional Chinese diet [cite]. As recommended by American Institute for Cancer Research and World Cancer Fund in the report Recommendations and Public Health and Policy Implication [Recommendations], diets high in fiber, rich in whole grains, and reduced or absent of red meats and processed meats reduce the risk of cancer development [29]. In contrast, in the recent decades, contemporary diets in Hong Kong [30] and many developed regions have shifted away from such diets to ones that are low in fibers and high in processed foods with exposure to food additives, refined sugar and hydrogenated fats [31]. In a prominent study compared cancer risks in rural and American Africans, the dietary habits of higher fibers, lower animal fats and protein in the rural Africans were associated with reduced cancer risks [32,33]. With that said, the reduced food diversity affects gut microbiota through dietary factors like high-fat, high-protein, low fiber that can trigger colon cancer . Ou et al. also reported microbial metabolite moderated by dietary intake can influence CRC risk [32]. Different dietary components may have various effects on the potential to develop CRC . Literature as of today is confusing on overall discussion of microbial-diet-host interaction involves metabolic cross-feeding of microbes, substrate degradation of dietary fibers, and microbiome as modulator to host physiology and behavior [34-36].

Traditional chinese diet

Dietary patterns and nutrients shape and reshape our gut microbiomes across lifespan, of which contribute to the initiation, development, or prevention of CRC [37-40]. One dietary approach in reducing CRC risk is directed at restoring the beneficial microbiota that leads to strengthening intestinal barrier against pathogenic bacteria, increasing intestinal motility, and lowering a pro-inflammatory state by adopting a diversified diet such like the Mediterranean diet [41-46]. Food diversity implies a wide range of food options covering the major food groups, such as described in the Mediterranean diet [30], are [i] high in vegetables and legumes, [ii] high in fruits, [iii] high in grains, [iv] moderate proteins from plants over animal, and [v] moderate dairy, which shares some characteristics of a traditional Chinese diet and translates to providing great sources of proteins, carbohydrates, fats, and the equally important micronutrients to optimize the bodily functions. Woo et al. revealed the dietary habits of Chinese population in four major cities, evaluated using the Mediterranean Diet Score, were compatible if not more adhering to the Mediterranean diet than the Greek population, whilst the cuisines varied yet remained culturally distinctive. The only sub-population with less adherence was the younger generation and men in Hong Kong, with 50% and 51% scored high, respectively [30]. The MDS described in Woo’s stool was indicative of the preservation of a more traditional Chinses dietary habit, being the population with 80% high scores resided in a rural Chinese region.

Conclusion

Considering a global westernization, many of the dietary and lifestyle recommendations are to promote a diversified dietary pattern to strengthen gut health, which is closely related to gut microbiota. Hippocrates once said, “All disease begins in the gut.” while not absolutely but it remains true to many diseases that trillions of microbes live on our skin and within our body are crucial to human health. Despite the lack of causation between microbiota and cancer, no single food can one-handedly prevent inflammation but relies on the synergetic effect of a diversified food consumption in compliance with the dietary guidelines to improve the overall anti-inflammatory prospects of the host [47-51] and advances the success rate of cultivating a healthy gut by creating a balancing microbiota environment. With further mechanistic studies to understand the multi-axial microbial-diet-host interaction, we hope to deduce a microbiota-driven dietary recommendation decision tree to optimize the growth and balance of gut microbiota soon.

Author contributions

WL was responsible for the conception, literature review, drafting and revising the manuscript. All authors reviewed and commented on subsequent drafts of the manuscript.

1. Allemani C, Matsuda T, Di Carlo V, Harewood R, Matz M, et al. (2018) Global surveillance of trends in cancer survival 2000-14 (CONCORD-3): analysis of individual records for 37 513 025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries. Lancet 391: 1023-1075. Link: https://bit.ly/3pycPT7
2. GlobalCan (2018) All Cancers Incidence and ortality Rates.
3. Lichtenstein P, Holm NV, Verkasalo PK, Iliadou A, Kaprio J, et al.  (2000) Environmental and heritable factors in the causation of cancer--analyses of cohorts of twins from Sweden, Denmark, and Finland. N Engl J Med  343: 78-85. Link: https://bit.ly/3lFq5mv
4. Samadder NJ, Jasperson K, Burt RW (2015) Hereditary and common familial colorectal cancer: evidence for colorectal screening. Dig Dis Sci 60: 734-747. Link: https://bit.ly/2IIkgGS
5. The L. GLOBOCAN 2018: counting the toll of cancer. Lancet 392: 985. Link:
6. Kong HAH (2017) Hong Kong Cancer Registry Top ten cancers 2017 2017. Link:
7. Department CaS, Health Do, Hong Kong Cancer Registry HA. Colorectal Cancer 2017. Available from: Link:
8. Ahn J, Sinha R, Pei Z, Dominianni C, Wu J, et al. (2013) Human gut microbiome and risk for colorectal cancer. Journal of the National Cancer Institute 105: 1907-1911. Link: https://bit.ly/3fdVMRK
9. Lozupone CA, Knight R (2008) Species divergence and the measurement of microbial diversity. FEMS microbiology reviews. 32: 557-578. Link: https://bit.ly/2IH6bcj
10. Cozen W, Yu Y, Hwang A, Ma B, Buchanan L, et al. (2017) Association between fecal microbiome and colon adenomas and hyperplastic polyps in monozygotic twins. Twin Research and Human Genetics 20: 620. Link: https://bit.ly/2UxJEBB
11. Xu S, Yin W, Zhang Y, Lv Q, Yang Y, et al. (2020) Foes or Friends? Bacteria Enriched in the Tumor Microenvironment of Colorectal Cancer. Cancers 12: 372. Link: https://bit.ly/3f6iLhj
12. Yang Y, Li L, Wang Y, Chen M, Huang J, et al. (2019) The gut microbiome-mediated proinflammatory macrophages recruitment to promote colon tumorigenesis. European Journal of Immunology 49: 1383.
13. Liang JQ, Chan FKL, Sung JJY, Yu J (2019) Fecal bacteria act as novel biomarkers for non-invasive diagnosis of colorectal neoplasm. Digestion 99: 104.
14. Cynthia S, Garrett WS (2014) Microbes, Microbiota, and Colon Cancer. Cell Host & Microbe 15: 317-328. Link: https://bit.ly/32Sv8ZE
15. Tilg H, Adolph TE, Gerner RR, Moschen AR (2018) The Intestinal Microbiota in Colorectal Cancer. Cancer Cell 33: 954-964. Link: https://bit.ly/3nswlib
16. Liang JQ, Li T, Nakatsu G, Chen YX, Yau TO, et al. (2019) A novel faecal Lachnoclostridium marker for the non-invasive diagnosis of colorectal adenoma and cancer. Gut  microbiota. Link: https://bit.ly/3nuBHt3
17. Yu J, Feng Q, Wong SH, Zhang D, Liang QY, et al. (2017) Metagenomic analysis of faecal microbiome as a tool towards targeted non-invasive biomarkers for colorectal cancer. Gut 66: 70-78. Link: https://bit.ly/2UyqL1d
18. Liang Q, Chiu J, Chen Y, Huang Y, Higashimori A, et al.  (2017) Fecal Bacteria Act as Novel Biomarkers for Noninvasive Diagnosis of Colorectal Cancer. Clin Cancer Res 23: 2061-2070. Link: https://bit.ly/2IH1HTi
19. Yu J, Feng Q, Wong SH, Zhang D, Liang Qy, et al. (2017) Metagenomic analysis of faecal microbiome as a tool towards targeted non-invasive biomarkers for colorectal cancer. Gut 66: 70-78. Link: https://bit.ly/3nCyGY1  
20. Schwabe RF, Jobin C (2013) The microbiome and cancer. Nat Rev Cancer 13: 800-812. Link: https://bit.ly/32Pb2ze  
21. Ijaz UZ, Quince C, Hanske L, Loman N, Calus ST, et al.  (2017) The distinct features of microbial 'dysbiosis' of Crohn's disease do not occur to the same extent in their unaffected, genetically-linked kindred. PLoS One 12: e0172605. Link: https://bit.ly/3f4BY39  
22. Jurjus A, Zeenny MN, Eid A, Chams S, Jurjus R (2015) Inflammation in colorectal cancer inflammatory bowel disease, and diabetes mellitus: The link. FASEB Journal Conference: Experimental Biology 29. Link: https://bit.ly/3kDWicT
23. de Almeida CV, Taddei A, Amedei A () The controversial role of Enterococcus faecalis in colorectal cancer. Therap Adv Gastroenterol 11: 1756284818783606. Link: https://bit.ly/38QftxC
24. Hersoug LG, Møller P, Loft S (2018) Role of microbiota-derived lipopolysaccharide in adipose tissue inflammation, adipocyte size and pyroptosis during obesity. Nutr Res Rev  31: 153-163. Link: https://bit.ly/3fixA0F  
25. Umoh FI, Kato I, Ren J, Wachowiak PL, Ruffin MT, et al. (2016) Markers of systemic exposures to products of intestinal bacteria in a dietary intervention study. Eur J Nutr 55: 793-798. Link: https://bit.ly/32SbNrt  
26. Balfegó M, Canivell S, Hanzu FA, Sala-Vila A, Martínez-Medina M, et al. (2016) Effects of sardine-enriched diet on metabolic control, inflammation and gut microbiota in drug-naïve patients with type 2 diabetes: a pilot randomized trial. Lipids Health Dis. 15: 78. Link: https://bit.ly/32SOTQO  
27. Awoyemi A, Trøseid M, Arnesen H, Solheim S, Seljeflot I (2019) Effects of dietary intervention and n-3 pufa supplementation on markers of gut-related inflammation and their association with cardiovascular events in a high-risk population. Atherosclerosis. 286: 53-59. Link: https://bit.ly/32RK4ag  
28. Irrazabal T, Belcheva A, Girardin SE, Martin A, Philpott DJ (2014) The multifaceted role of the intestinal microbiota in colon cancer. Mol Cell  54: 309-320. Link: https://bit.ly/2INU0L2  
29. Clinton SK, Giovannucci EL, Hursting SD (2019) The World Cancer Research Fund/American Institute for Cancer Research Third Expert Report on Diet, Nutrition, Physical Activity, and Cancer: Impact and Future Directions. J Nutr 150: 663-671. Link: https://bit.ly/2UCPS2M  
30. Woo J, Woo KS, Leung SS, Chook P, Liu B, et al. (2001) The Mediterranean score of dietary habits in Chinese populations in four different geographical areas. Eur J Clin Nutr 55: 215-220. Link: https://bit.ly/35COzHN
31. Jew S, AbuMweis SS, Jones PJ (2009) Evolution of the human diet: linking our ancestral diet to modern functional foods as a means of chronic disease prevention. J Med Food 12: 925-934. Link: https://bit.ly/36G0mEh
32. Ou J, Carbonero F, Zoetendal EG, DeLany JP, Wang M, et al. (2013) Diet, microbiota, and microbial metabolites in colon cancer risk in rural Africans and African Americans. Am J Clin Nutr  98: 111-120. Link: https://bit.ly/2IGytDZ
33. O’Keefe SJD, Li JV, Lahti L, Ou J, Carbonero F, et al. (2015) Fat, fibre and cancer risk in African Americans and rural Africans. Nat Commun 6: 6342. Link: https://bit.ly/3f3zthw
34. Cryan JF, O'Riordan KJ, Cowan CSM, Sandhu KV, Bastiaanssen TFS, et al. (2019) The Microbiota-Gut-Brain Axis. Physiol Rev 99: 1877-2013. Link: https://bit.ly/36LoG7E
35. Henriques SF, Serra L, Francisco AP, Carvalho-Santos Z, Baltazar C, et al. (2019) Metabolic cross-feeding allows a gut microbial community to overcome detrimental diets and alter host behaviour. bioRxiv 821892. Link: https://bit.ly/3lDv1IL
36. Kim M, Vogtmann E, Ahlquist DA, Devens ME, Kisiel JB, et al. (2020) Fecal Metabolomic Signatures in Colorectal Adenoma Patients Are Associated with Gut Microbiota and Early Events of Colorectal Cancer Pathogenesis. mBio 11: e03186-19. Link: https://bit.ly/3f9RQBw
37. Desai MS, Seekatz AM, Koropatkin NM, Kamada N, Hickey CA, et al. (2016) A Dietary Fiber-Deprived Gut Microbiota Degrades the Colonic Mucus Barrier and Enhances Pathogen Susceptibility. Cell 167: 1339-1353.e21. Link: https://bit.ly/3pCmPL1
38. Ríos-Covián D, Ruas-Madiedo P, Margolles A, Gueimonde M, de Los Reyes-Gavilán CG (2016) Intestinal short chain fatty acids and their link with diet and human health. Front Microbiol  7: 185. Link: https://bit.ly/3kEu1Tt
39. Fernández J, Redondo-Blanco S, Gutiérrez-del-Río I, Miguélez EM, Villar CJ, et al. (2016) Colon microbiota fermentation of dietary prebiotics towards short-chain fatty acids and their roles as anti-inflammatory and antitumour agents: A review. Journal of Functional Foods 25: 511-522. Link: https://bit.ly/2INN6VN
40. Tomás-Barberán FA, Selma MV, Espín JC (2016) Interactions of gut microbiota with dietary polyphenols and consequences to human health. Curr Opin Clin Nutr Metab Care 19:471-476. Link: https://bit.ly/3pzmcC4
41. Gutierrez-Diaz I, Fernandez-Navarro T, Sanchez B, Margolles A, Gonzalez S (2016) Mediterranean diet and faecal microbiota: a transversal study. Food Funct 7: 2347-2356. Link: https://bit.ly/3nwmIyZ
42. De Filippis F, Pellegrini N, Vannini L, Jeffery IB, La Storia A, et al. (2016) High-level adherence to a Mediterranean diet beneficially impacts the gut microbiota and associated metabolome. Gut 65: 1812-1821. Link: https://bit.ly/3pyjX1T
43. Bifulco M (2015) Mediterranean diet: the missing link between gut microbiota and inflammatory diseases. Eur J Clin Nutr  69: 1078. Link: https://bit.ly/3kCYZeD
44. Donovan MG, Selmin OI, Doetschman TC, Romagnolo DF (2017) Mediterranean Diet: Prevention of Colorectal Cancer. Frontiers in Nutrition 4: 59. Link: https://bit.ly/3f6h6Z7
45. Piazzi G, Prossomariti A, Baldassarre M, Montagna C, Vitaglione P, et al.  (2019) A Mediterranean Diet Mix Has Chemopreventive Effects in a Murine Model of Colorectal Cancer Modulating Apoptosis and the Gut Microbiota. Front Oncol  9: 140. Link: https://bit.ly/3lIgpry
46. Perez-Jimenez J, Diaz-Rubio ME, Saura-Calixto F (2015) Contribution of Macromolecular Antioxidants to Dietary Antioxidant Capacity: A Study in the Spanish Mediterranean Diet. Plant Foods Hum Nutr 70: 365-370. Link: https://bit.ly/2IJCEik
47. Sivaprakasam S, Ganapathy PK, Ramachandran S, Kottapalli KR, Vadivel G (2019) Deficiency of dietary fiber in Slc5a8-null mice promotes bacterial dysbiosis and inflammatory milieu in colon. Can J Gastroenterol Hepatol 79. Link: https://bit.ly/3lHcM59
48. Uribe G, Rourke R, Villeger R, Golovko G, Khanipov K, et al. (2018) Cancer derived Escherichia coli induces tumor-promoting inflammatory cytokine IL-6 in cancer associated fibroblasts (CAFs) in a NF-kappaB/BRD4 dependent manner. Cancer Research Conference 78.
49. Vanegas SM, Meydani M, Barnett JB, Goldin B, Kane A, 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. Link: https://bit.ly/38PIzgM
50. Huang W, Zhou L, Guo H, Xu Y, Xu Y (2017) The role of short-chain fatty acids in kidney injury induced by gut-derived inflammatory response. Metabolism 68: 20-30. Link: https://bit.ly/3lDtQsP
51. Fedorak R, Hotte N, Park H, Keshteli AH, Ginter R, et al. (2016) 546 High sugar diets promote an inflammatory microbiota and reduce gene expression related to intestinal barrier function. Gastroenterology S114-S115. Link: https://bit.ly/36K6OKu