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Cancer Immunology, Immunotherapy

Erschienen in:

26.10.2023 | Review

Human anaerobic microbiome: a promising and innovative tool in cancer prevention and treatment by targeting pyruvate metabolism

verfasst von: Hari Om, Umesh Chand, Pramod Kumar Kushawaha

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 12/2023

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Abstract

Introduction

Even in present-day times, cancer is one of the most fatal diseases. People are overwhelmed by pricey chemotherapy, immunotherapy, and other costly cancer therapies in poor and middle-income countries. Cancer cells grow under anaerobic and hypoxic conditions. Pyruvate is the final product of the anaerobic glycolysis pathway, and many cancer cells utilize pyruvate for their growth and development. The anaerobic microbiome produces many anti-cancer substances that can act as anti-tumor agents and are both feasible and of low cost. There are different mechanisms of action of the anaerobic microbiome, such as the production of short-chain fatty acids (SCFAs), and competition for the anaerobic environment includes the metabolic product pyruvate to form lactic acid for energy.

Key findings

In this review, we have summarized the role of the metabolic approach of the anaerobic human microbiome in cancer prevention and treatment by interfering with cancer metabolite pyruvate. SCFAs possess decisive outcomes in condoning almost all the hallmarks of cancer and helping the spread of cancer to other body parts. Studies have demonstrated the impact and significance of using SCFA, which results from anaerobic bacteria, as an anti-cancer agent. Anaerobic bacteria-based cancer therapy has become a promising approach to treat cancer using obligate and facultative anaerobic bacteria because of their ability to penetrate and increase in an acidic hypoxic environment.

Significance

This review attempts to provide the interconnection of cancer metabolism and anaerobic microbiome metabolism with a focus on pyruvate metabolism to understand and design unique anaerobic microbiota-based therapy for cancer patients.

Graphical abstract

Chen X, Winckler B, Lu M, Cheng H, Yuan Z, Yang Y, Jin L, Ye W (2015) Oral Microbiota and risk for esophageal squamous cell carcinoma in a high-risk area of China. PLoS ONE 10(12):e0143603. https://doi.org/10.1371/journal.pone.0143603CrossRefPubMedPubMedCentral

Ren Z, Li A, Jiang J, Zhou L, Yu Z, Lu H, Xie H, Chen X, Shao L, Zhang R, Xu S, Zhang H, Cui G, Chen X, Sun R, Wen H, Lerut JP, Kan Q, Li L, Zheng S (2019) Gut microbiome analysis as a tool towards targeted non-invasive biomarkers for early hepatocellular carcinoma. Gut 68(6):1014–1023. https://doi.org/10.1136/gutjnl-2017-315084CrossRefPubMed

Lu K, Dong S, Wu X, Jin R, Chen H (2021) Probiotics in Cancer. Front Oncol. https://doi.org/10.3389/fonc.2021.638148CrossRefPubMedPubMedCentral

Śliżewska K, Markowiak-Kopeć P, Śliżewska W (2020) The role of probiotics in cancer prevention. Cancers 13(1):20. https://doi.org/10.3390/cancers13010020CrossRefPubMedPubMedCentral

Shi Y, Lian K, Jia J (2022) Apigenin suppresses the warburg effect and stem-like properties in SOSP-9607 cells by inactivating the PI3K/Akt/mTOR signaling pathway. Evidence-Based Complement Altern Med 2022:1–10. https://doi.org/10.1155/2022/3983637CrossRef

Teng Y, Auld D, Pratap Mishra S et al (2020) Pyruvate Kinase M2 and cancer: the role of PKM2 in promoting tumorigenesis. Front Oncol 1:159. https://doi.org/10.3389/fonc.2020.00159CrossRef

Kruspig B, Zhivotovsky B, Gogvadze V (2014) Mitochondrial substrates in cancer: drivers or passengers? Mitochondrion 19:8–19. https://doi.org/10.1016/J.MITO.2014.08.007CrossRefPubMed

Peng Z, Cheng S, Kou Y et al (2020) The Gut microbiome is associated with clinical response to Anti-PD-1/PD-L1 immunotherapy in gastrointestinal cancer. Cancer Immunol Res 8:1251–1261. https://doi.org/10.1158/2326-6066.CIR-19-1014CrossRefPubMed

Ranjbar R, Vahdati SN, Tavakoli S, Khodaie R, Behboudi H (2021) Immunomodulatory roles of microbiota-derived short-chain fatty acids in bacterial infections. Biomed Pharmacoth 141:111817. https://doi.org/10.1016/j.biopha.2021.111817CrossRef

10.

Smith DM, Snow DE, Rees E et al (2010) Evaluation of the bacterial diversity of pressure ulcers using bTEFAP pyrosequencing. BMC Med Genomics. https://doi.org/10.1186/1755-8794-3-41CrossRefPubMedPubMedCentral

11.

Foster JW, Aliabadi Z, Slonczewski J (2021) Microbiology : the human experience, 2nd edn. W. W. Norton & Company, New York

12.

Coutzac C, Jouniaux JM, Paci A et al (2020) Systemic short chain fatty acids limit antitumor effect of CTLA-4 blockade in hosts with cancer. Nat Commun. https://doi.org/10.1038/s41467-020-16079-xCrossRefPubMedPubMedCentral

13.

Rastall RA (2004) Bacteria in the gut: friends and foes and how to alter the balance. J Nutr 134(8 Suppl):2022S-2026S. https://doi.org/10.1093/jn/134.8.2022SCrossRefPubMed

14.

Molska M, Reguła J (2019) Potential mechanisms of probiotics action in the prevention and treatment of colorectal cancer. Nutrients 11(10):2453. https://doi.org/10.3390/nu11102453CrossRefPubMedPubMedCentral

15.

Liang Y, Li Q, Liu Y, Guo Y, Li Q (2023) Awareness of intratumoral bacteria and their potential application in cancer treatment. Discov Oncol 14(1):57. https://doi.org/10.1007/s12672-023-00670-xCrossRefPubMedPubMedCentral

16.

Zhou W, Sailani MR, Contrepois K et al (2019) Longitudinal multi-omics of host–microbe dynamics in prediabetes. Nature 569:663–671. https://doi.org/10.1038/s41586-019-1236-xCrossRefPubMedPubMedCentral

17.

Urbaniak C, Gloor GB, Brackstone M, Scott L, Tangney M, Reid G (2016) The microbiota of breast tissue and its association with breast cancer. Appl Environ Microbiol 82(16):5039–5048. https://doi.org/10.1128/AEM.01235-16CrossRefPubMedPubMedCentral

18.

Sfanos KS, Markowski MC, Peiffer LB, Ernst SE, White JR, Pienta KJ, Antonarakis ES, Ross AE (2018) Compositional differences in gastrointestinal microbiota in prostate cancer patients treated with androgen axis-targeted therapies. Prostate Cancer Prostatic Dis 21(4):539–548. https://doi.org/10.1038/s41391-018-0061-xCrossRefPubMedPubMedCentral

19.

Sivaprakasam S, Bhutia YD, Yang S, Ganapathy V (2018) Short-chain fatty acid transporters: role in colonic homeostasis. Compr Physiol 8:299–314. https://doi.org/10.1002/cphy.c170014CrossRef

20.

Bultman SJ (2017) Interplay between diet, gut microbiota, epigenetic events, and colorectal cancer. Mol Nutr Food Res. https://doi.org/10.1002/mnfr.201500902CrossRefPubMed

21.

Dróżdż M, Makuch S, Cieniuch G, Woźniak M, Ziółkowski P (2020) Obligate and facultative anaerobic bacteria in targeted cancer therapy: current strategies and clinical applications. Life Sci 261:118296. https://doi.org/10.1016/j.lfs.2020.118296CrossRefPubMed

22.

Matsushita M, Fujita K, Hayashi T et al (2021) Gut microbiota–derived short-chain fatty acids promote prostate cancer growth via IGF1 signaling. Cancer Res 81:4014–4026. https://doi.org/10.1158/0008-5472.CAN-20-4090CrossRefPubMed

23.

Matthews GM, Howarth GS, Butler RN (2012) Short-chain fatty acids induce apoptosis in colon cancer cells associated with changes to intracellular redox state and glucose metabolism. Chemotherapy 58:102–109. https://doi.org/10.1159/000335672CrossRefPubMed

24.

Kim CH, Park J, Kim M (2014) Gut microbiota-derived short-chain fatty acids, T cells, and inflammation. Immune Netw 14(6):277–288. https://doi.org/10.4110/in.2014.14.6.277CrossRefPubMedPubMedCentral

25.

Yin J, Xiaozheng H, Chen T (2022) Can salt-tolerant sludge mitigate the salt inhibition to acidogenic fermentation of food waste? insight into volatile fatty acid production and microbial community. Waste Biomass Valoriz 13:2121–2136. https://doi.org/10.1007/s12649-021-01654-0CrossRef

26.

Koh A, De Vadder F, Kovatcheva-Datchary P, Bäckhed F (2016) From dietary fiber to host physiology: short-chain fatty acids as key bacterial metabolites. Cell 165(6):1332–1345. https://doi.org/10.1016/j.cell.2016.05.041CrossRefPubMed

27.

Luo A, Li S, Wang X et al (2021) Cefazolin improves anesthesia and surgery-induced cognitive impairments by modulating blood-brain barrier function, gut bacteria and short chain fatty acids. Front Aging Neurosci 13:680. https://doi.org/10.3389/FNAGI.2021.748637/BIBTEXCrossRef

28.

Ibragimova S, Ramachandran R, Ali FR et al (2021) Dietary patterns and associated microbiome changes that promote oncogenesis. Front Cell Dev Biol 9:3210. https://doi.org/10.3389/FCELL.2021.725821/BIBTEXCrossRef

29.

Ciani M, Comitini F, Mannazzu I (2013) Fermentation. Encycl Ecol. https://doi.org/10.1016/B978-0-12-409548-9.00693-XCrossRef

30.

Keshteli AH, Madsen KL, Dieleman LA (2019) Diet in the pathogenesis and management of ulcerative colitis; a review of randomized controlled dietary interventions. Nutrients 11(7):1498. https://doi.org/10.3390/nu11071498CrossRefPubMedPubMedCentral

31.

Ward B (2015) Bacterial energy metabolism. Molecular Medical Microbiology, 2nd edn, Vol 1–3. Academic Press, Cambridge. pp 201–233. https://doi.org/10.1016/B978-0-12-397169-2.00011-1

32.

Blouin JM, Penot G, Collinet M et al (2011) Butyrate elicits a metabolic switch in human colon cancer cells by targeting the pyruvate dehydrogenase complex. Int J Cancer 128:2591–2601. https://doi.org/10.1002/ijc.25599CrossRefPubMed

33.

Al-Hilu SA, Al-Shujairi WH (2020) Dual role of bacteria in carcinoma: stimulation and inhibition. Int J Microbiol 2020:4639761. https://doi.org/10.1155/2020/4639761CrossRefPubMedPubMedCentral

34.

Peng M, Reichmann G, Biswas D (2015) Lactobacillus casei and its byproducts alter the virulence factors of foodborne bacterial pathogens. J Funct Foods. https://doi.org/10.1016/j.jff.2015.03.055CrossRef

35.

Peng M, Biswas D (2017) Short chain and polyunsaturated fatty acids in host gut health and foodborne bacterial pathogen inhibition. Crit Rev Food SciNutr. https://doi.org/10.1080/10408398.2016.1203286CrossRef

36.

Pagliari D, Gambassi G, Piccirillo CA, Cianci R (2017) The intricate link among gut “immunological niche”, microbiota, and xenobiotics in intestinal pathology. Mediators Inflamm. https://doi.org/10.1155/2017/8390595CrossRefPubMedPubMedCentral

37.

Venegas DP, De La Fuente MK, Landskron G et al (2019) Short chain fatty acids (SCFAs)-mediated gut epithelial and immune regulation and its relevance for inflammatory bowel diseases. Front Immunol 10:424615. https://doi.org/10.3389/fimmu.2019.00277CrossRef

38.

Qian X-H, Xie R-Y, Liu X-L et al (2021) Mechanisms of short-chain fatty acids derived from gut microbiota in alzheimer’s disease. Aging Dis 13(4):1252. https://doi.org/10.14336/AD.2021.1215CrossRef

39.

Carretta MD, Quiroga J, López R, Hidalgo MA, Burgos RA (2021) Participation of short-chain fatty acids and their receptors in gut inflammation and colon cancer. Front Physiol 12:662739. https://doi.org/10.3389/fphys.2021.662739CrossRefPubMedPubMedCentral

40.

Kim CH, Park J, Kim M (2014) Gut microbiota-derived short-chain fatty acids, T cells, and inflammation. Immune Netw 14:277–288. https://doi.org/10.4110/IN.2014.14.6.277CrossRefPubMedPubMedCentral

41.

Cho YM, Fujita Y, Kieffer TJ (2014) Glucagon-like peptide-1: glucose homeostasis and beyond. Annu Rev Physiol 76:535–559. https://doi.org/10.1146/annurev-physiol-021113-170315CrossRefPubMed

42.

Mirzaei R, Afaghi A, Babakhani S, Sohrabi MR, Hosseini-Fard SR, Babolhavaeji K, Khani Ali Akbari S, Yousefimashouf R, Karampoor S (2021) Role of microbiota-derived short-chain fatty acids in cancer development and prevention. Biomed Pharmacoth 139:111619. https://doi.org/10.1016/j.biopha.2021.111619CrossRef

43.

Jafari SM, Nabavi SM, Silva AS (2021) Nutraceuticals and cancer signaling. Springer, New YorkCrossRef

44.

Gorlach S, Wagner W, Podsdek A et al (2011) Procyanidins from Japanese quince (Chaenomeles japonica) fruit induce apoptosis in human colon cancer caco-2 cells in a degree of polymerization- dependent manner. Nutr Cancer 63:1348–1360. https://doi.org/10.1080/01635581.2011.608480CrossRefPubMed

45.

Hinnebusch BF, Meng S, Wu JT et al (2002) The effects of short-chain fatty acids on human colon cancer cell phenotype are associated with histone hyperacetylation. J Nutr 132:1012–1017. https://doi.org/10.1093/JN/132.5.1012CrossRefPubMed

46.

Kim K, Kwon O, Ryu TY et al (2019) Propionate of a microbiota metabolite induces cell apoptosis and cell cycle arrest in lung cancer. Mol Med Rep 20:1569–1574. https://doi.org/10.3892/mmr.2019.10431CrossRefPubMedPubMedCentral

47.

Markowiak-Kopeć P, Śliżewska K (2020) The effect of probiotics on the production of short-chain fatty acids by human intestinal microbiome. Nutrients 12(4):1107. https://doi.org/10.3390/nu12041107CrossRefPubMedPubMedCentral

48.

van der Hee B, Wells JM (2021) Microbial regulation of host physiology by short-chain fatty acids. Trends Microbiol 29(8):700–712. https://doi.org/10.1016/j.tim.2021.02.001CrossRefPubMed

49.

Sanchez-Diaz PC, Chang JC, Moses ES et al (2017) Ubiquitin carboxyl-terminal esterase L1 (UCHL1) is associated with stem-like cancer cell functions in pediatric high-grade glioma. PLoS ONE. https://doi.org/10.1371/JOURNAL.PONE.0176879CrossRefPubMedPubMedCentral

50.

Gu BH, Kim M, Yun CH (2021) Regulation of gastrointestinal immunity by metabolites. Nutrients 13:167. https://doi.org/10.3390/NU13010167CrossRefPubMedPubMedCentral

51.

Funamizu N, Lacy CR, Kamada M et al (2015) MicroRNA-203 induces apoptosis by upregulating puma expression in colon and lung cancer cells. Int J Oncol 47:1981–1988. https://doi.org/10.3892/ijo.2015.3178CrossRefPubMed

52.

Wang G, Yu Y, Wang YZ, Wang JJ, Guan R, Sun Y, Shi F, Gao J, Fu XL (2019) Role of SCFAs in gut microbiome and glycolysis for colorectal cancer therapy. J Cell Physiol 234(10):17023–17049. https://doi.org/10.1002/jcp.28436CrossRefPubMed

53.

Wan MY, Liu LL, Dou DQ (2022) Comparative study on medicinal natures (qi) of black ginseng, red ginseng, and ginseng leaves based on typical deficiency-heat syndrome rat model. Evidence-based Complement Altern Med. https://doi.org/10.1155/2022/5194987CrossRef

54.

Pham CH, Lee JE, Yu J et al (2021) Anticancer effects of propionic acid inducing cell death in cervical cancer cells. Molecules. https://doi.org/10.3390/molecules26164951CrossRefPubMedPubMedCentral

55.

Adom D, Nie D (2013) Regulation of autophagy by short chain fatty acids in colon cancer cells. InTechCrossRef

56.

Valentine RJ, Coughlan KA, Ruderman NB, Saha AK (2014) Insulin inhibits AMPK activity and phosphorylates AMPK Ser 485/491 through Akt in hepatocytes, myotubes and incubated rat skeletal muscle. Arch Biochem Biophys. https://doi.org/10.1016/j.abb.2014.08.013CrossRefPubMedPubMedCentral

57.

Tang Y, Chen Y, Jiang H, Nie D (2011) Short-chain fatty acids induced autophagy serves as an adaptive strategy for retarding mitochondria-mediated apoptotic cell death. Cell Death Differ 18:602–618. https://doi.org/10.1038/cdd.2010.117CrossRefPubMed

58.

Kobayashi M, Mikami D, Uwada J et al (2018) A short-chain fatty acid, propionate, enhances the cytotoxic effect of cisplatin by modulating GPR41 signaling pathways in HepG2 cells. Oncotarget 9(59):31342CrossRefPubMedPubMedCentral

59.

Reczek CR, Chandel NS (2017) The two faces of reactive oxygen species in cancer. Annu Rev Cancer Biol. https://doi.org/10.1146/annurev-cancerbio-041916-065808CrossRef

60.

Krick S, Kotlyarov S (2022) Role of short-chain fatty acids produced by gut microbiota in innate lung immunity and pathogenesis of the heterogeneous course of chronic obstructive pulmonary disease. Int J Mol Sci 23:4768. https://doi.org/10.3390/IJMS23094768CrossRef

61.

Park J, Kim M, Kang SG et al (2015) Short-chain fatty acids induce both effector and regulatory T cells by suppression of histone deacetylases and regulation of the mTOR-S6K pathway. Mucosal Immunol 8:80–93. https://doi.org/10.1038/mi.2014.44CrossRefPubMed

62.

Ramires LC, Santos GS, Ramires RP et al (2022) The association between gut microbiota and osteoarthritis: does the disease begin in the gut? Int J Mol Sci 23:1494. https://doi.org/10.3390/IJMS23031494CrossRefPubMedPubMedCentral

63.

Aho VTE, Houser MC, Pereira PAB et al (2021) Relationships of gut microbiota, short-chain fatty acids, inflammation, and the gut barrier in Parkinson’s disease. MolNeurodegener. https://doi.org/10.1186/s13024-021-00427-6CrossRef

64.

Rossi T, Vergara D, Fanini F, Maffia M, Bravaccini S, Pirini F (2020) Microbiota-derived metabolites in tumor progression and metastasis. Int J Mol Sci 21(16):5786. https://doi.org/10.3390/ijms21165786CrossRefPubMedPubMedCentral

65.

Casanova MR, Azevedo-Silva J, Rodrigues LR, Preto A (2018) Colorectal cancer cells increase the production of short chain fatty acids by propionibacterium freudenreichii impacting on cancer cells survival. Front Nutr. https://doi.org/10.3389/fnut.2018.00044CrossRefPubMedPubMedCentral

66.

Zhao X, Sun P, Liu M et al (2022) Deoxynivalenol exposure inhibits biosynthesis of milk fat and protein by impairing tight junction in bovine mammary epithelial cells. Ecotoxicol Environ Saf 237:113504. https://doi.org/10.1016/j.ecoenv.2022.113504CrossRefPubMed

67.

Gupta KH, Nowicki C, Giurini EF, Marzo AL, Zloza A (2021) Bacterial-based cancer therapy (BBCT): recent advances, current challenges, and future prospects for cancer immunotherapy. Vaccines 9(12):1497. https://doi.org/10.3390/vaccines9121497CrossRefPubMedPubMedCentral

68.

Duong MTQ, Qin Y, You SH, Min JJ (2019) Bacteria-cancer interactions: bacteria-based cancer therapy. Exp Mol Med. https://doi.org/10.1038/S12276-019-0297-0CrossRefPubMedPubMedCentral

Titel: Human anaerobic microbiome: a promising and innovative tool in cancer prevention and treatment by targeting pyruvate metabolism
verfasst von: Hari Om
Umesh Chand
Pramod Kumar Kushawaha
Publikationsdatum: 26.10.2023
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Immunology, Immunotherapy / Ausgabe 12/2023
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-023-03551-y

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Human anaerobic microbiome: a promising and innovative tool in cancer prevention and treatment by targeting pyruvate metabolism

Abstract

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Key findings

Significance

Graphical abstract

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Abstract

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