Top

Published in:

01-02-2022 | Respiratory Microbiota | Original Contribution

Lactobacillus coryniformis MXJ32 administration ameliorates azoxymethane/dextran sulfate sodium-induced colitis-associated colorectal cancer via reshaping intestinal microenvironment and alleviating inflammatory response

Authors: Tao Wang, Leshan Zhang, Panpan Wang, Yilin Liu, Gangtu Wang, Yuanyuan Shan, Yanglei Yi, Yuan Zhou, Bianfang Liu, Xin Wang, Xin Lü

Published in: European Journal of Nutrition | Issue 1/2022

Abstract

Purpose

Gut microbiota has been reported to contribute to either prevent or promote colorectal cancer (CRC), and treatment with probiotics might be a promising intervention method. The present study aimed to evaluate the potential anti-CRC effects of Lactobacillus coryniformis MXJ32 on a colitis-associated (CA)-CRC mouse model.

Methods

The CA-CRC mouse model was induced by a single intraperitoneal injection of 10 mg/kg azoxymethane and followed by three 7-day cycles of 2% dextran sulfate sodium in drinking water with a 14-day recovery period. Mice were supplemented with L. coryniformis MXJ32 by oral gavage (1 × 10⁹ CFU/day/mouse). The CA-CRC attenuating effects of this probiotic were assessed via intestinal barrier integrity, inflammation, and gut microenvironment.

Results

Treatment with L. coryniformis MXJ32 could significantly inhibit the total number of tumors and the average tumor diameter. This probiotic administration prevented the damage of intestinal barrier function by enhancing the expression of tight junction proteins (Occludin, Claudin-1, and ZO-1) and recovering the loss of goblet cells. Moreover, L. coryniformis MXJ32 alleviated intestinal inflammation via down-regulating the expression of inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-γ, and IL-17a) and chemokines (Cxcl1, Cxcl2, Cxcl3, Cxcl5, and Ccl7). In addition, L. coryniformis MXJ32 supplementation increased the abundance of some beneficial bacteria (such as SCFAs-producing bacteria, Lactobacillus, Bifidobacterium, Akkermansia, and Faecalibaculum) and decreased the abundance of some harmful bacteria (such as pro-inflammatory bacteria, Desulfovibrio and Helicobacter), which in turn attenuated the overexpression of inflammation.

Conclusion

Lactobacillus coryniformis MXJ32 could effectively ameliorate CA-CRC via regulating intestinal microenvironment, alleviating inflammation, and intestinal barrier damage, which further suggested that L. coryniformis MXJ32 could be considered as a functional food ingredient for the alleviation of CA-CRC.

Graphic abstract

Available only for authorised users

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68(6):394–424. https://doi.org/10.3322/caac.21492CrossRefPubMed

Yin L, Meng Z, Zhang YX, Hu KK, Chen WY, Han KB, Wu BY, You R, Li CH, Jin Y, Guan YQ (2018) Bacillus spore-based oral carriers loading curcumin for the therapy of colon cancer. J Control Release 271:31–44. https://doi.org/10.1016/j.jconrel.2017.12.013CrossRefPubMed

Yue YC, Ye K, Lu J, Wang XY, Zhang SW, Liu L, Yang BY, Nassar K, Xu XX, Pang XY, Lv JP (2020) Probiotic strain Lactobacillus plantarum YYC-3 prevents colon cancer in mice by regulating the tumour microenvironment. Biomed Pharmacother 127:1–8. https://doi.org/10.1016/j.biopha.2020.110159CrossRef

O’Brien JM (2000) Environmental and heritable factors in the causation of cancer: analyses of cohorts of twins from Sweden, Denmark, and Finland, by P. Lichtenstein, N.V. Holm, P.K. Verkasalo, A. Iliadou, J. Kaprio, M. Koskenvuo, E. Pukkala, A. Skytthe, and K. Hemminki. N Engl J Med 343:78-84, 2000. Surv Ophthalmol 45(2):167–168. https://doi.org/10.1016/s0039-6257(00)00165-xCrossRefPubMed

Czene K, Lichtenstein P, Hemminki K (2002) Environmental and heritable causes of cancer among 9.6 million individuals in the Swedish family-cancer database. Int J Cancer 99(2):260–266. https://doi.org/10.1002/ijc.10332CrossRefPubMed

Wong SH, Yu J (2019) Gut microbiota in colorectal cancer: mechanisms of action and clinical applications. Nat Rev Gastroenterol Hepatol 16(11):690–704. https://doi.org/10.1038/s41575-019-0209-8CrossRefPubMed

Donaldson GP, Lee SM, Mazmanian SK (2016) Gut biogeography of the bacterial microbiota. Nat Rev Microbiol 14(1):20–32. https://doi.org/10.1038/nrmicro3552CrossRefPubMed

Tian Y, Zhou Y, Huang SS, Li J, Zhao K, Li XH, Wen XC, Li XA (2019) Fecal microbiota transplantation for ulcerative colitis: a prospective clinical study. BMC Gastroenterol 19:12. https://doi.org/10.1186/s12876-019-1010-4CrossRef

Uronis JM, Muhlbauer M, Herfarth HH, Rubinas TC, Jones GS, Jobin C (2009) Modulation of the intestinal microbiota alters colitis-associated colorectal cancer susceptibility. PLoS ONE 4(6):e6026. https://doi.org/10.1371/journal.pone.0006026CrossRefPubMedPubMedCentral

10.

Li YH, Wang S, Sun Y, Xu WQ, Zheng HN, Wang Y, Tang Y, Gao XW, Song C, Long Y, Liu JY, Liu L, Mei QB (2020) Apple polysaccharide protects ICR mice against colitis associated colorectal cancer through the regulation of microbial dysbiosis. Carbohydr Polym 230:10. https://doi.org/10.1016/j.carbpol.2019.115726CrossRef

11.

Jacouton E, Chain F, Sokol H, Langella P, Bermudez-Humaran LG (2017) Probiotic strain Lactobacillus casei BL23 prevents colitis-associated colorectal cancer. Front Immunol 8:10. https://doi.org/10.3389/fimmu.2017.01553CrossRef

12.

Silveira DSC, Veronez LC, Lopes LC, Anatriello E, Brunaldi MO, Pereira-da-Silva G (2020) Lactobacillus bulgaricus inhibits colitis-associated cancer via a negative regulation of intestinal inflammation in azoxymethane/dextran sodium sulfate model. World J Gastroenterol 26(43):6782–6794. https://doi.org/10.3748/wjg.v26.i43.6782CrossRefPubMedPubMedCentral

13.

Eslami M, Yousefi B, Kokhaei P, Hemati M, Nejad ZR, Arabkari V, Namdar A (2019) Importance of probiotics in the prevention and treatment of colorectal cancer. J Cell Physiol 234(10):17127–17143. https://doi.org/10.1002/jcp.28473CrossRefPubMed

14.

Lu X, Yi LH, Dang J, Dang Y, Liu BF (2014) Purification of novel bacteriocin produced by Lactobacillus coryniformis MXJ32 for inhibiting bacterial foodborne pathogens including antibiotic-resistant microorganisms. Food Control 46:264–271. https://doi.org/10.1016/j.foodcont.2014.05.028CrossRef

15.

Wang T, Sun H, Chen J, Luo L, Gu Y, Wang X, Shan Y, Yi Y, Liu B, Zhou Y, Lu X (2021) Anti-adhesion effects of Lactobacillus strains on Caco-2 cells against Escherichia Coli and their application in ameliorating the symptoms of dextran sulfate sodium-induced colitis in mice. Probiotics Antimicrob Proteins. https://doi.org/10.1007/s12602-021-09774-8CrossRefPubMedPubMedCentral

16.

Chen WG, Liu FL, Ling ZX, Tong XJ, Xiang C (2012) Human intestinal lumen and mucosa-associated microbiota in patients with colorectal cancer. PLoS ONE 7(6):9. https://doi.org/10.1371/journal.pone.0039743CrossRef

17.

Yao DB, Dong M, Dai CL, Wu SD (2019) Inflammation and inflammatory cytokine contribute to the initiation and development of ulcerative colitis and its associated cancer. Inflamm Bowel Dis 25(10):1595–1602. https://doi.org/10.1093/ibd/izz149CrossRefPubMed

18.

Sun J, Chen H, Kan J, Gou YR, Liu J, Zhang X, Wu XN, Tang SX, Sun R, Qian CL, Zhang NF, Niu FX, Jin CH (2020) Anti-inflammatory properties and gut microbiota modulation of an alkali-soluble polysaccharide from purple sweet potato in DSS-induced colitis mice. Int J Biol Macromol 153:708–722. https://doi.org/10.1016/j.ijbiomac.2020.03.053CrossRefPubMed

19.

Yang HX, Wang WC, Romano KA, Gu M, Sanidad KZ, Kim D, Yang J, Schmidt B, Panigrahy D, Pei RS, Martin DA, Ozay EI, Wang YX, Song MY, Bolling BW, Xiao H, Minter LM, Yang GY, Liu ZH, Rey FE, Zhang GD (2018) A common antimicrobial additive increases colonic inflammation and colitis-associated colon tumorigenesis in mice. Sci Transl Med 10(443):10. https://doi.org/10.1126/scitranslmed.aan4116CrossRef

20.

Xie F, Zhang H, Zheng C, Shen XF (2020) Costunolide improved dextran sulfate sodium-induced acute ulcerative colitis in mice through NF-kappa B, STAT1/3, and Akt signaling pathways. Int Immunopharmacol 84:10. https://doi.org/10.1016/j.intimp.2020.106567CrossRef

21.

Wang T, Yan H, Lu YY, Li X, Wang X, Shan YY, Yi YL, Liu BF, Zhou Y, Lu X (2020) Anti-obesity effect of Lactobacillus rhamnosus LS-8 and Lactobacillus crustorum MN047 on high-fat and high-fructose diet mice base on inflammatory response alleviation and gut microbiota regulation. Eur J Nutr 59(6):2709–2728. https://doi.org/10.1007/s00394-019-02117-yCrossRefPubMed

22.

Song H, Wang WY, Shen B, Jia H, Hou ZY, Chen P, Sun YW (2018) Pretreatment with probiotic Bifico ameliorates colitis-associated cancer in mice: transcriptome and gut flora profiling. Cancer Sci 109(3):666–677. https://doi.org/10.1111/cas.13497CrossRefPubMedPubMedCentral

23.

Cammarota R, Bertolini V, Pennesi G, Bucci EO, Gottardi O, Garlanda C, Laghi L, Barberis MC, Sessa F, Noonan DM, Albini A (2010) The tumor microenvironment of colorectal cancer: Stromal TLR-4 expression as a potential prognostic marker. J Transl Med 8:16. https://doi.org/10.1186/1479-5876-8-112CrossRef

24.

van Staa TP, Card T, Logan RF, Leufkens HG (2005) 5-Aminosalicylate use and colorectal cancer risk in inflammatory bowel disease: a large epidemiological study. Gut 54(11):1573–1578. https://doi.org/10.1136/gut.2005.070896CrossRefPubMedPubMedCentral

25.

Flores BM, O’Connor A, Moss AC (2017) Impact of mucosal inflammation on risk of colorectal neoplasia in patients with ulcerative colitis: a systematic review and meta-analysis. Gastrointest Endosc 86(6):1006-1011.e1008. https://doi.org/10.1016/j.gie.2017.07.028CrossRefPubMed

26.

Wang DZ, DuBois RN, Richmond A (2009) The role of chemokines in intestinal inflammation and cancer. Curr Opin Pharmacol 9(6):688–696. https://doi.org/10.1016/j.coph.2009.08.003CrossRefPubMedPubMedCentral

27.

Wang K, Jin X, Li Q, Sawaya ACHF, Le Leu RK, Conlon MA, Wu L, Hu F (2018) Propolis from different geographic origins decreases intestinal inflammation and Bacteroides spp. populations in a model of DSS-induced colitis. Mol Nutr Food Res 62(17):1800080. https://doi.org/10.1002/mnfr.201800080CrossRef

28.

Khazaie K, Zadeh M, Khan MW, Bere P, Gounari F, Dennis K, Blatner NR, Owen JL, Klaenhammer TR, Mohamadzadeh M (2012) Abating colon cancer polyposis by Lactobacillus acidophilus deficient in lipoteichoic acid. Proc Natl Acad Sci USA 109(26):10462–10469. https://doi.org/10.1073/pnas.1207230109CrossRefPubMedPubMedCentral

29.

Soroosh A, Rankin CR, Polytarchou C, Lokhandwala ZA, Patel A, Chang L, Pothoulakis C, Iliopoulos D, Padua DM (2019) miR-24 Is elevated in ulcerative colitis patients and regulates intestinal epithelial barrier function. Am J Pathol 189(9):1763–1774. https://doi.org/10.1016/j.ajpath.2019.05.018CrossRefPubMedPubMedCentral

30.

Katinios G, Casado-Bedmar M, Walter SA, Vicario M, Gonzalez-Castro AM, Bednarska O, Soderholm JD, Hjortswang H, Keita AV (2020) Increased colonic epithelial permeability and mucosal eosinophilia in ulcerative colitis in remission compared with irritable bowel syndrome and health. Inflamm Bowel Dis 26(7):974–984. https://doi.org/10.1093/ibd/izz328CrossRefPubMedPubMedCentral

31.

Robrahn L, Jiao L, Cramer T (2020) Barrier integrity and chronic inflammation mediated by HIF-1 impact on intestinal tumorigenesis. Cancer Lett 490:186–192. https://doi.org/10.1016/j.canlet.2020.07.002CrossRefPubMed

32.

Sun J, Kato I (2016) Gut microbiota, inflammation and colorectal cancer. Genes Dis 3(2):130–143. https://doi.org/10.1016/j.gendis.2016.03.004CrossRefPubMedPubMedCentral

33.

Zeisel MB, Dhawan P, Baumert TF (2019) Tight junction proteins in gastrointestinal and liver disease. Gut 68(3):547–561. https://doi.org/10.1136/gutjnl-2018-316906CrossRefPubMed

34.

Kang MS, Martin A (2017) Microbiome and colorectal cancer: unraveling host-microbiota interactions in colitis-associated colorectal cancer development. Semin Immunol 32(C):3–13. https://doi.org/10.1016/j.smim.2017.04.003CrossRefPubMed

35.

Gao ZG, Guo BM, Gao RY, Zhu QC, Wu W, Qin HL (2015) Probiotics modify human intestinal mucosa-associated microbiota in patients with colorectal cancer. Mol Med Report 12(4):6119–6127. https://doi.org/10.3892/mmr.2015.4124CrossRef

36.

Wierzbicka A, Mankowska-Wierzbicka D, Mardas M, Stelmach-Mardas M (2021) Role of probiotics in modulating human gut microbiota populations and activities in patients with colorectal cancer-a systematic review of clinical trials. Nutrients 13(4):13. https://doi.org/10.3390/nu13041160CrossRef

37.

Peck BCE, Mah AT, Pitman WA, Ding SL, Lund PK, Sethupathy P (2017) Functional transcriptomics in diverse intestinal epithelial cell types reveals robust microRNA sensitivity in intestinal stem cells to microbial status. J Biol Chem 292(7):2586–2600. https://doi.org/10.1074/jbc.M116.770099CrossRefPubMedPubMedCentral

38.

Oh NS, Lee JY, Kim YT, Kim SH, Lee JH (2020) Cancer-protective effect of a synbiotic combination between Lactobacillus gasseri 505 and a Cudrania tricuspidata leaf extract on colitis-associated colorectal cancer. Gut Microbes 12(1):20. https://doi.org/10.1080/19490976.2020.1785803CrossRef

39.

Wang Q, Wang KC, Wu WR, Lv LX, Bian XY, Yang LY, Wang QQ, Li YT, Ye JH, Fang DQ, Wu JJ, Jiang XW, Xie JJ, Lu YM, Li LJ (2020) Administration of Bifidobacterium bifidum CGMCC 15068 modulates gut microbiota and metabolome in azoxymethane (AOM)/dextran sulphate sodium (DSS)-induced colitis-associated colon cancer (CAC) in mice. Appl Microbiol Biotechnol 104(13):5915–5928. https://doi.org/10.1007/s00253-020-10621-zCrossRefPubMed

40.

Fukata M, Chen A, Vamadevan AS, Cohen J, Breglio K, Krishnareddy S, Hsu D, Xu R, Harpaz N, Dannenberg AJ, Subbaramaiah K, Cooper HS, Itzkowitz SH, Abreu MT (2007) Toll-like receptor-4 promotes the development of colitis-associated colorectal tumors. Gastroenterology 133(6):1869–1881. https://doi.org/10.1053/j.gastro.2007.09.008CrossRefPubMed

41.

De Simone V, Franze E, Ronchetti G, Colantoni A, Fantini MC, Di Fusco D, Sica GS, Sileri P, MacDonald TT, Pallone F, Monteleone G, Stolfi C (2015) Th17-type cytokines, IL-6 and TNF-alpha synergistically activate STAT3 and NF-kB to promote colorectal cancer cell growth. Oncogene 34(27):3493–3503. https://doi.org/10.1038/onc.2014.286CrossRefPubMed

42.

Zagato E, Pozzi C, Bertocchi A, Schioppa T, Saccheri F, Guglietta S, Fosso B, Melocchi L, Nizzoli G, Troisi J, Marzano M, Oresta B, Spadoni I, Atarashi K, Carloni S, Arioli S, Fornasa G, Asnicar F, Segata N, Guglielmetti S, Honda K, Pesole G, Vermi W, Penna G, Rescigno M (2020) Endogenous murine microbiota member Faecalibaculum rodentium and its human homologue protect from intestinal tumour growth. Nat Microbiol 5(3):511–524. https://doi.org/10.1038/s41564-019-0649-5CrossRefPubMedPubMedCentral

43.

Gomes SD, Oliveira CS, Azevedo-Silva J, Casanova MR, Barreto J, Pereira H, Chaves SR, Rodrigues LR, Casal M, Corte-Real M, Baltazar F, Preto A (2020) The role of diet related short-chain fatty acids in colorectal cancer metabolism and survival: prevention and therapeutic implications. Curr Med Chem 27(24):4087–4108. https://doi.org/10.2174/0929867325666180530102050CrossRefPubMed

44.

Yao Y, Cai X, Fei W, Ye Y, Zhao M, Zheng C (2020) The role of short-chain fatty acids in immunity, inflammation and metabolism. Crit Rev Food Sci Nutr. https://doi.org/10.1080/10408398.2020.1854675CrossRefPubMed

45.

Li M, van Esch B, Wagenaar GTM, Garssen J, Folkerts G, Henricks PAJ (2018) Pro- and anti-inflammatory effects of short chain fatty acids on immune and endothelial cells. Eur J Pharmacol 831:52–59. https://doi.org/10.1016/j.ejphar.2018.05.003CrossRefPubMed

46.

Chang PV, Hao LM, Offermanns S, Medzhitov R (2014) The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition. Proc Natl Acad Sci USA 111(6):2247–2252. https://doi.org/10.1073/pnas.1322269111CrossRefPubMedPubMedCentral

47.

Singh N, Gurav A, Sivaprakasam S, Brady E, Padia R, Shi HD, Thangaraju M, Prasad PD, Manicassamy S, Munn DH, Lee JR, Offermanns S, Ganapathy V (2014) Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis. Immunity 40(1):128–139. https://doi.org/10.1016/j.immuni.2013.12.007CrossRefPubMedPubMedCentral

Title: Lactobacillus coryniformis MXJ32 administration ameliorates azoxymethane/dextran sulfate sodium-induced colitis-associated colorectal cancer via reshaping intestinal microenvironment and alleviating inflammatory response
Authors: Tao Wang
Leshan Zhang
Panpan Wang
Yilin Liu
Gangtu Wang
Yuanyuan Shan
Yanglei Yi
Yuan Zhou
Bianfang Liu
Xin Wang
Xin Lü
Publication date: 01-02-2022
Publisher: Springer Berlin Heidelberg
Keywords: Respiratory Microbiota
Colorectal Cancer
Colorectal Cancer
Published in: European Journal of Nutrition / Issue 1/2022
Print ISSN: 1436-6207
Electronic ISSN: 1436-6215
DOI: https://doi.org/10.1007/s00394-021-02627-8

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits

Illustration of figure on mountain summit/© Orapun / Stock.adobe.com, STEP AAG HeroTeaserCollection image/© Tarek / Generated with AI / Stock.adobe.com, ACC 2024 Pediatric and Congenital Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Pulmonary Vascular Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Valvular Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 HF and Cardiomyopathies: Year in Review/© 2024 American College of Cardiology, Woman out walking/© Seventyfour / stock.adobe.com (symbolic image with model), Woman checking smartwatch /© saltdium / stock.adobe.com (symbolic image with model), Cardiac catheterization/© Damian / stock.adobe.com

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

Graphic abstract

Please log in to get access to this content

Other articles of this Issue 1/2022

Micronutrients deficiences in patients after bariatric surgery

MFGM components promote gut Bifidobacterium growth in infant and in vitro

Correction to: Dietary total antioxidant capacity and mortality in the PREDIMED study

Correction to: Parental high‑fat high‑sugar diet programming and hypothalamus adipose tissue axis in male Wistar rats

Correction to: Aligning nutrient profiling with dietary guidelines: modifying the Nutri-Score algorithm to include whole grains

Correction to: The cost effectiveness of personalized dietary advice to increase protein intake in older adults with lower habitual protein intake: a randomized controlled trial

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

Highlights from the ACC 2024 Congress

ACC 2024 Congress Coverage