Abstract
Postbiotics are produced by microbes and have recently gained importance in the field of oncology due to their beneficial effects to the host, effectiveness against cancer cells, and their ability to suppress inflammation. In particular, butyrate dominates over all other postbiotics both in quantity and anticancer properties. Pancreatic cancer (PC), being one of the most malignant and lethal cancers, reported a decreased 5-year survival rate in less than 10% of the patients. PC causes an increased mortality rate due to its inability to be detected at an early stage but still a promising strategy for its diagnosis has not been achieved yet. It is necessary to diagnose Pancreatic cancer before the metastatic progression stage. The available blood biomarkers lack accurate and proficient diagnostic results. Postbiotic butyrate is produced by gut microbiota such as Rhuminococcus and Faecalibacterium it is involved in cell signalling pathways, autophagy, and cell cycle regulation, and reduction in butyrate concentration is associated with the occurrence of pancreatic cancer. The postbiotic butyrate is a potential biomarker that could detect PC at an early stage, before the metastatic progression stage. Thus, this review focused on the gut microbiota butyrate’s role in pancreatic cancer and the immuno-suppressive environment, its effects on histone deacetylase and other immune cells, microbes in major butyrate synthesis pathways, current biomarkers in use for Pancreatic Cancer.
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No datasets were generated or analysed during the current study.
Abbreviations
- AhR:
-
Aryl hydrocarbon receptor
- CA19–9:
-
Carbohydrate antigen 19 − 9
- CAR:
-
Chimeric antigen receptor
- CEA:
-
Carcinoembryonic antigen
- CTLA-4:
-
Cytotoxic T-lymphocyte-associated antigen 4
- CTLA-4:
-
Anti-cytotoxic T lymphocyte-associated antigen-4
- CTLs:
-
Cytotoxic T lymphocytes
- DNA:
-
Deoxyribose nucleic acid
- DUPAN-2:
-
Duke pancreatic monoclonal antigen type 2
- FDA:
-
Food and Drug Administration
- FISH:
-
Fluorescence in situ hybridization
- HDAC:
-
Histone deacetylase
- IMPACT:
-
Immunological multiparameter chip technology
- LTS:
-
Long-term survivors
- MDSCs:
-
Myeloid-derived suppressor cells
- NFAT:
-
Nuclear factor of activated T-cells
- PC:
-
Pancreatic Cancer
- PCoA:
-
Principal coordinate analysis
- PD-1:
-
Programmed cell death protein 1
- PDAC:
-
Pancreatic ductal adenocarcinoma
- qPCR:
-
Quantitative polymerase chain reaction
- RNA:
-
Ribonucleic acid
- STS:
-
Short-term survivors
- T-bet:
-
Transcription factor of T box
- TAM:
-
Tumor-associated macrophages
- TIME:
-
Tumor immune microenvironment
- TIMP-1:
-
Tissue inhibitor matrix metalloproteinase 1
- Treg:
-
T regulatory cells
References
Abdul Rahman R, Lamarca A, Hubner RA, Valle JW, McNamara MG (2021) The Microbiome as a potential target for therapeutic manipulation in pancreatic Cancer. Cancers (Basel) 13(15):3779. https://doi.org/10.3390/cancers13153779
Abue M, Yokoyama M, Shibuya R, Tamai K, Yamaguchi K, Sato I, Tanaka N, Hamada S, Shimosegawa T, Sugamura K, Satoh K (2015) Circulating mir-483-3p and miR-21 is highly expressed in plasma of pancreatic cancer. Int J Oncol 46(2):539–547. https://doi.org/10.3892/ijo.2014.2743
Adewiah S, Abubakar A, Yusuf F (2018) IDDF2018-ABS-0023 butyrate acid as a potential marker for the diversity of gut microbiota in colorectal cancer patients. Clin. Gastroenterol. BMJ Publishing Group Ltd and British Society of Gastroenterology, pp A341–A34
Agrawal S (2017) Potential prognostic biomarkers in pancreatic juice of resectable pancreatic ductal adenocarcinoma. World J Clin Oncol 8(3):255. https://doi.org/10.5306/wjco.v8.i3.255
Aguirre AJ, Bardeesy N, Sinha M, Lopez L, Tuveson DA, Horner J et al (2003) Activated Kras and Ink4a/Arf deficiency cooperate to produce metastatic pancreatic ductal adenocarcinoma. Genes Dev 17:3112–3126. https://doi.org/10.1101/gad.1158703
Ahuja M, Schwartz DM, Tandon M, Son A, Zeng M, Swaim W, Eckhaus M, Hoffman V, Cui Y, Xiao B, Worley PF, Muallem S (2017) Orai1-mediated antimicrobial secretion from pancreatic Acini shapes the gut microbiome and regulates gut innate immunity. Cell Metab 25(3):635–646. https://doi.org/10.1016/j.cmet.2017.02.007
Alemar B, Izetti P, Gregório C, Macedo GS, Castro MAA, Osvaldt AB, Matte U, Ashton-Prolla P (2016) miRNA-21 and miRNA-34a are potential minimally invasive biomarkers for the diagnosis of pancreatic ductal adenocarcinoma. Pancreas 45(1):84–92. https://doi.org/10.1097/MPA.0000000000000383
Arends J, Bachmann P, Baracos V, Barthelemy N, Bertz H, Bozzetti F, Fearon K, Hütterer E, Isenring E, Kaasa S, Krznaric Z, Laird B, Larsson M, Laviano A, Mühlebach S, Muscaritoli M, Oldervoll L, Ravasco P, Solheim T, Strasser F, de van der Schueren M, Preiser J-C (2017) ESPEN guidelines on nutrition in cancer patients. Clin Nutr 36(1):11–48. https://doi.org/10.1016/j.clnu.2016.07.015
Barker HA, Kahn JM, Hedrick L (1982) Pathway of lysine degradation in Fusobacterium nucleatum. J Bacteriol 152(1):201–207. https://doi.org/10.1128/jb.152.1.201-207.1982
Bastos AR, Pereira-Marques J, Ferreira RM, Figueiredo C (2023) Harnessing the microbiome to reduce pancreatic cancer burden. Cancers (Basel) 15(9):2629. https://doi.org/10.3390/cancers15092629
Campbell PJ, Yachida S, Mudie LJ, Stephens PJ, Pleasance ED, Stebbings LA, Morsberger LA, Latimer C, McLaren S, Lin M-L, McBride DJ, Varela I, Nik-Zainal SA, Leroy C, Jia M, Menzies A, Butler AP, Teague JW, Griffin CA, Burton J, Swerdlow H, Quail MA, Stratton MR, Iacobuzio-Donahue C, Futreal PA (2010) The patterns and dynamics of genomic instability in metastatic pancreatic cancer. Nature 467(7319):1109–1113. https://doi.org/10.1038/nature09460
Cancer Stat Facts : Pancreatic Cancer. https://seer.cancer.gov/statfacts/html/pancreas.html. Accessed on 15 Feb 2023
Cancer.Net Editorial Board (2023) Pancreatic Cancer: stages. Cancer.Net
Cao Y, Gao X, Zhang W (2011) Dietary fiber enhances TGF-β signaling and growth inhibition in the gut. Dietary Fiber enhances TGF-β signaling and growth inhibition in the gut. Am J Physiol Gastrointest Liver Physiol 301:G156–G164
Carreras-Torres R, Johansson M, Gaborieau V, Haycock P, Wade KH, Relton CL, Martin RM, Davey Smith G, Brennan P (2017) The role of obesity, type 2 diabetes, and metabolic factors in pancreatic cancer: a Mendelian randomization study. JNCI: JNatl Cancer Inst 109(9). https://doi.org/10.1093/jnci/djx012
Chapman MAS, Hutton M, Grahn MF, Williams NS (1997) Metabolic adaptation of terminal ileal mucosa after construction of an ileoanal pouch. Br J Surg 84(1):71–73. https://doi.org/10.1002/bjs.1800840127
Charkhchi P, Cybulski C, Gronwald J, Wong FO, Narod SA, Akbari MR (2020) CA125 and ovarian Cancer: a Comprehensive Review. Cancers (Basel) 12(12):3730. https://doi.org/10.3390/cancers12123730
Chen J, Zhao KN, Vitetta L (2019) Effects of intestinal microbial-elaborated butyrate on oncogenic signaling pathways. Nutrients 11(5):1026. https://doi.org/10.3390/nu11051026
Chen IM, Willumsen N, Dehlendorff C, Johansen AZ, Jensen BV, Hansen CP, Hasselby JP, Bojesen SE, Pfeiffer P, Nielsen SE, Holländer NH, Yilmaz MK, Karsdal M, Johansen JS (2020) Clinical value of serum hyaluronan and propeptide of type III collagen in patients with pancreatic cancer. Int J Cancer 146(10):2913–2922. https://doi.org/10.1002/ijc.32751
Chen J, Zhao KN, Vitetta L (2019) Effects of intestinal microbial-elaborated butyrate on oncogenic signaling pathways. Nutrients 11. https://doi.org/10.3390/nu11051026
Chim SSC, Shing TKF, Hung ECW, Leung T, Lau T, Chiu RWK, Dennis Lo YM (2008) Detection and characterization of placental MicroRNAs in maternal plasma. Clin Chem 54(3):482–490. https://doi.org/10.1373/clinchem.2007.097972
Ciernikova S, Sevcikova A, Drgona L, Mego M (2023) Modulating the gut microbiota by probiotics, prebiotics, postbiotics, and fecal microbiota transplantation: an emerging trend in cancer patient care. Biochimica et Biophysica Acta (BBA). - Rev Cancer 1878(6):188990. https://doi.org/10.1016/j.bbcan.2023.188990
Costello E, Greenhalf W, Neoptolemos JP (2012) New biomarkers and targets in pancreatic cancer and their application to treatment. Nat Rev Gastroenterol Hepatol 9(8):435–444. https://doi.org/10.1038/nrgastro.2012.119
Coutzac C, Jouniaux J-M, Paci A, Schmidt J, Mallardo D, Seck A, Asvatourian V, Cassard L, Saulnier P, Lacroix L, Woerther P-L, Vozy A, Naigeon M, Nebot-Bral L, Desbois M, Simeone E, Mateus C, Boselli L, Grivel J, Soularue E, Lepage P, Carbonnel F, Ascierto PA, Robert C, Chaput N (2020) Systemic short chain fatty acids limit antitumor effect of CTLA-4 blockade in hosts with cancer. Nat Commun 11(1):2168. https://doi.org/10.1038/s41467-020-16079-x
Davie JR (2003) Inhibition of histone deacetylase activity by Butyrate. J Nutr 133(7):2485S–2493S. https://doi.org/10.1093/jn/133.7.2485S
de Sousa Cavalcante L, Monteiro G (2014) Gemcitabine: metabolism and molecular mechanisms of action, sensitivity and chemoresistance in pancreatic cancer. Eur J Pharmacol 741:8–16. https://doi.org/10.1016/j.ejphar.2014.07.041
del Castillo E, Meier R, Chung M, Koestler DC, Chen T, Paster BJ, Charpentier KP, Kelsey KT, Izard J, Michaud DS (2019) The microbiomes of pancreatic and duodenum tissue overlap and are highly subject specific but differ between pancreatic cancer and noncancer subjects. Cancer Epidemiol Biomarkers Prev 28(2):370–383. https://doi.org/10.1158/1055-9965.EPI-18-0542
Dittmar RL, Liu S, Tai MC, Rajapakshe K, Huang Y, Longton G, DeCapite C, Hurd MW, Paris PL, Kirkwood KS, Coarfa C, Maitra A, Brand RE, Killary AM, Sen S (2021) Plasma miRNA biomarkers in limited volume samples for detection of early-stage pancreatic cancer. Cancer Prev Res 14(7):729–740. https://doi.org/10.1158/1940-6207.CAPR-20-0303
Dong D, Jia L, Zhang L, Ma N, Zhang A, Zhou Y, Ren L (2018) Periostin and CA242 as potential diagnostic serum biomarkers complementing CA19.9 in detecting pancreatic cancer. Cancer Sci 109(9):2841–2851. https://doi.org/10.1111/cas.13712
Dong Y, Zhang K, Wei J, Ding Y, Wang X, Hou H, Wu J, Liu T, Wang B, Cao H (2023) Gut microbiota-derived short-chain fatty acids regulate gastrointestinal tumor immunity: a novel therapeutic strategy? Front Immunol 14. https://doi.org/10.3389/fimmu.2023.1158200
Dou H, Sun G, Zhang L (2019) CA242 as a biomarker for pancreatic cancer and other diseases. Prog Mol BiolTransl Sci 162:229–239. https://doi.org/10.1016/bs.pmbts.2018.12.007
Egawa S, Takeda K, Fukuyama S, Motoi F, Sunamura M, Matsuno S (2004) Clinicopathological aspects of small pancreatic cancer. Pancreas 28(3):235–240. https://doi.org/10.1097/00006676-200404000-00004
Erin P (2022) Five-year pancreatic Cancer survival rate increases to 11%. In: Pancreat Cancer Action Netw, https://pancan.org/news/five-year-pancreatic-cancer-survival-rate-increases-to-11/
Fan X, Alekseyenko AV, Wu J, Peters BA, Jacobs EJ, Gapstur SM, Purdue MP, Abnet CC, Stolzenberg-Solomon R, Miller G, Ravel J, Hayes RB, Ahn J (2018) Human oral microbiome and prospective risk for pancreatic cancer: a population-based nested case-control study. Gut 67(1):120–127. https://doi.org/10.1136/gutjnl-2016-312580
Farrell JJ, Zhang L, Zhou H, Chia D, Elashoff D, Akin D, Paster BJ, Joshipura K, Wong DTW (2012) Variations of oral microbiota are associated with pancreatic diseases including pancreatic cancer. Gut 61(4):582–588. https://doi.org/10.1136/gutjnl-2011-300784
Fong W, Li Q, Yu J (2020) Gut microbiota modulation: a novel strategy for prevention and treatment of colorectal cancer. Oncogene 39(26):4925–4943. https://doi.org/10.1038/s41388-020-1341-1
Fu X, Liu Z, Zhu C, Mou H, Kong Q (2019) Nondigestible carbohydrates, butyrate, and butyrate-producing bacteria. Crit Rev Food Sci Nutr 59(sup1):S130–S152. https://doi.org/10.1080/10408398.2018.1542587
Geller LT, Barzily-Rokni M, Danino T, Jonas OH, Shental N, Nejman D, Gavert N, Zwang Y, Cooper ZA, Shee K, Thaiss CA, Reuben A, Livny J, Avraham R, Frederick DT, Ligorio M, Chatman K, Johnston SE, Mosher CM, Brandis A, Fuks G, Gurbatri C, Gopalakrishnan V, Kim M, Hurd MW, Katz M, Fleming J, Maitra A, Smith DA, Skalak M, Bu J, Michaud M, Trauger SA, Barshack I, Golan T, Sandbank J, Flaherty KT, Mandinova A, Garrett WS, Thayer SP, Ferrone CR, Huttenhower C, Bhatia SN, Gevers D, Wargo JA, Golub TR, Straussman R (2017) Potential role of intratumor bacteria in mediating tumor resistance to the chemotherapeutic drug gemcitabine. Science (1979) 357(6356):1156–1160. https://doi.org/10.1126/science.aah5043
Gleeson FC, Jeraldo P, Levy MJ, Murphy SJ, Mendes-Soares H, Karagouga G, Mccune AF, Garcia GarciaDeparedes A, Kipp BR, Song SD, Khanna S, Pardi DS, Chia N (2022) Composition, diversity and potential utility of intervention-naïve pancreatic cancer intratumoral microbiome signature profiling via endoscopic ultrasound. Gut 71(2):441–443. https://doi.org/10.1136/gutjnl-2021-324031
Haglund C (1986) Tumour marker antigen CA125 in pancreatic cancer: a comparison with CA19-9 and CEA. Br J Cancer 54(6):897–901. https://doi.org/10.1038/bjc.1986.259
Hall C, Clarke L, Pal A, Buchwald P, Eglinton T, Wakeman C, Frizelle F (2019) A review of the role of carcinoembryonic antigen in clinical practice. Ann Coloproctol 35(6):294–305. https://doi.org/10.3393/ac.2019.11.13
He Y, Fu L, Li Y, Wang W, Gong M, Zhang J, Dong X, Huang J, Wang Q, Mackay CR, Fu Y-X, Chen Y, Guo X (2021) Gut microbial metabolites facilitate anticancer therapy efficacy by modulating cytotoxic CD8 + T cell immunity. Cell Metab 33(5):988–1000e7. https://doi.org/10.1016/j.cmet.2021.03.002
Huang Y, Zhu N, Zheng X, Liu Y, Lu H, Yin X, Hao H, Tan Y, Wang D, Hu H, Liang Y, Li X, Hu Z, Yin Y (2022) Intratumor microbiome analysis identifies positive association between megasphaera and survival of chinese patients with pancreatic ductal adenocarcinomas. Front Immunol 13. https://doi.org/10.3389/fimmu.2022.785422
Hujoel PP, Drangsholt M, Spiekerman C, Weiss NS (2003) An exploration of the periodontitis–cancer association. Ann Epidemiol 13(5):312–316. https://doi.org/10.1016/S1047-2797(02)00425-8
Hullar MAJ, Burnett-Hartman AN, Lampe JW (2014) Gut microbes, diet, and cancer. Cancer Treat Res 159:377–399. https://doi.org/10.1007/978-3-642-38007-5_22
Ishige F, Hoshino I, Iwatate Y, Chiba S, Arimitsu H, Yanagibashi H, Nagase H, Takayama W (2020) MIR1246 in body fluids as a biomarker for pancreatic cancer. Sci Rep 10(1):8723. https://doi.org/10.1038/s41598-020-65695-6
Javadrashid D, Baghbanzadeh A, Derakhshani A, Leone P, Silvestris N, Racanelli V et al (2021) Pancreatic cancer signaling pathways, genetic alterations, and tumor microenvironment: the barriers affecting the method of treatment. Biomedicines 9. https://doi.org/10.3390/biomedicines9040373
Joergensen MT, Brünner N, De Muckadell OBS (2010) Comparison of circulating MMP-9, TIMP-1 and CA19-9 in the detection of pancreatic cancer. Anticancer Res 30(2):587–592 PMID: 20332475
Kane LE, Mellotte GS, Mylod E, O’Brien RM, O’Connell F, Buckley CE, Arlow J, Nguyen K, Mockler D, Meade AD, Ryan BM, Maher SG (2022) Diagnostic accuracy of blood-based biomarkers for pancreatic cancer: a systematic review and meta-analysis. Cancer Res Commun 2(10):1229–1243. https://doi.org/10.1158/2767-9764.CRC-22-0190
Kartal E, Schmidt TSB, Molina-Montes E, Rodríguez-Perales S, Wirbel J, Maistrenko OM, Akanni WA, AlashkarAlhamwe B, Alves RJ, Carrato A, Erasmus H-P, Estudillo L, Finkelmeier F, Fullam A, Glazek AM, Gómez-Rubio P, Hercog R, Jung F, Kandels S, Kersting S, Langheinrich M, Márquez M, Molero X, Orakov A, Van Rossum T, Torres-Ruiz R, Telzerow A, Zych K, Benes V, Zeller G, Trebicka J, Real FX, Malats N, Bork P (2022) A faecal microbiota signature with high specificity for pancreatic cancer. Gut 71(7):1359–1372. https://doi.org/10.1136/gutjnl-2021-324755
Kaur S, Baine MJ, Jain M, Sasson AR, Batra SK (2012) Early diagnosis of pancreatic cancer: challenges and new developments. Biomark Med 6(5):597–612. https://doi.org/10.2217/bmm.12.69
Kespohl M, Vachharajani N, Luu M, Harb H, Pautz S, Wolff S, Sillner N, Walker A, Schmitt-Kopplin P, Boettger T, Renz H, Offermanns S, Steinhoff U, Visekruna A (2017) The microbial metabolite butyrate induces expression of Th1-associated factors in CD4 + T cells. Front Immunol 8. https://doi.org/10.3389/fimmu.2017.01036
Kibbie JJ, Dillon SM, Thompson TA, Purba CM, McCarter MD, Wilson CC (2021) Butyrate directly decreases human gut lamina propria CD4 T cell function through histone deacetylase (HDAC) inhibition and GPR43 signaling. Immunobiology 226(5):152126. https://doi.org/10.1016/j.imbio.2021.152126
Kiss B, Mikó E, Sebő É, Toth J, Ujlaki G, Szabó J, Uray K, Bai P, Árkosy P (2020) Oncobiosis and microbial metabolite signaling in pancreatic adenocarcinoma. Cancers (Basel) 12(5):1068. https://doi.org/10.3390/cancers12051068
Le Large TYS, Meijer LL, Paleckyte R, Boyd LNC, Kok B, Wurdinger T, Schelfhorst T, Piersma SR, Pham TV, van Grieken NCT, Zonderhuis BM, Daams F, van Laarhoven HWM, Bijlsma MF, Jimenez CR, Giovannetti E, Kazemier G (2020) Combined expression of plasma thrombospondin-2 and CA19-9 for diagnosis of pancreatic cancer and distal cholangiocarcinoma: a proteome approach. Oncologist 25(4):e634–e643. https://doi.org/10.1634/theoncologist.2019-0680
Lee M (2021) Harness the functions of gut microbiome in tumorigenesis for cancer treatment. Cancer Commun 41(10):937–967. https://doi.org/10.1002/cac2.12200
Li S, Fuhler GM, BN N, Jose T, Bruno MJ, Peppelenbosch MP, Konstantinov SR (2017) Pancreatic cyst fluid harbors a unique microbiome. Microbiome 5(1):147. https://doi.org/10.1186/s40168-017-0363-6
Louis P, Flint HJ (2009) Diversity, metabolism and microbial ecology of butyrate-producing bacteria from the human large intestine. FEMS Microbiol Lett 294(1):1–8. https://doi.org/10.1111/j.1574-6968.2009.01514.x
Lu¨hrs H, Lu¨hrs L, Gerke T, Boxberger F, Backhaus K, Melcher R et al (2001) Butyrate inhibits interleukin-1-mediated nuclear factor-kappa B activation in human epithelial cells. Dig Dis Sci 46:1968–1973
Lührs H, Gerke T, Müller JG, Melcher R, Schauber J, Boxberger F et al (2002) Butyrate inhibits NF-μB activation in lamina propria macrophages of patients with ulcerative colitis. Scand J Gastroenterol 37:458–466
Luo G, Fan Z, Cheng H, Jin K, Guo M, Lu Y, Yang C, Fan K, Huang Q, Long J, Liu L, Xu J, Lu R, Ni Q, Warshaw AL, Liu C, Yu X (2018) New observations on the utility of CA19-9 as a biomarker in Lewis negative patients with pancreatic cancer. Pancreatology 18(8):971–976. https://doi.org/10.1016/j.pan.2018.08.003
Luo G, Jin K, Deng S, Cheng H, Fan Z, Gong Y, Qian Y, Huang Q, Ni Q, Liu C, Yu X (2021) Roles of CA19-9 in pancreatic cancer: biomarker, predictor and promoter. Biochim Biophys Acta Rev Cancer 1875(2):188409. https://doi.org/10.1016/j.bbcan.2020.188409
Luo W, Wang J, Chen H, Ye L, Qiu J, Liu Y, Wang R, Weng G, Liu T, Su D, Tao J, Ding C, You L, Zhang T (2023) Epidemiology of pancreatic cancer: new version, new vision. Chin J Cancer Res 35(5):438–450. https://doi.org/10.21147/j.issn.1000-9604.2023.05.03
Luu M, Riester Z, Baldrich A, Reichardt N, Yuille S, Busetti A, Klein M, Wempe A, Leister H, Raifer H, Picard F, Muhammad K, Ohl K, Romero R, Fischer F, Bauer CA, Huber M, Gress TM, Lauth M, Danhof S, Bopp T, Nerreter T, Mulder IE, Steinhoff U, Hudecek M, Visekruna A (2021) Microbial short-chain fatty acids modulate CD8 + T cell responses and improve adoptive immunotherapy for cancer. Nat Commun 12(1):4077. https://doi.org/10.1038/s41467-021-24331-1
Macfarlane S, Macfarlane GT (2003) Regulation of short-chain fatty acid production. Proc Nutr Soc 62(1):67–72. https://doi.org/10.1079/PNS2002207
Malhotra P, Palanisamy R, Caparros-Martin JA, Falasca M (2023) Bile acids and microbiota interplay in pancreatic cancer. Cancers (Basel) 15(14):3573. https://doi.org/10.3390/cancers15143573
Manegold P, Lai KKY, Wu Y, Teo JL, Lenz HJ, Genyk YS et al (2018) Differentiation therapy targeting the β-catenin/CBP interaction in pancreatic cancer. Cancers (Basel) 10. https://doi.org/10.3390/cancers10040095
Martin-Gallausiaux C, Béguet-Crespel F, Marinelli L (2018) Butyrate produced by gut commensal bacteria activates TGF-beta1 expression through the transcription factor SP1 in human intestinal epithelial cells. Sci Rep 8:9742
Martinez-Bosch N, Vinaixa J, Navarro P (2018) Immune evasion in pancreatic cancer: from mechanisms to therapy. Cancers (Basel) 10(1):6. https://doi.org/10.3390/cancers10010006
Mendez R, Kesh K, Arora N, Di Martino L, McAllister F, Merchant N, Banerjee S, Banerjee S (2020) Microbial dysbiosis and polyamine metabolism as predictive markers for early detection of pancreatic cancer. Carcinogenesis 41(5):561–570. https://doi.org/10.1093/carcin/bgz116
Meng Q, Shi S, Liang C, Liang D, Xu W, Ji S, Zhang B, Ni Q, Xu J, Yu X (2017) Diagnostic and prognostic value of carcinoembryonic antigen in pancreatic cancer: a systematic review and meta-analysis. Onco Targets Ther 10:4591–4598. https://doi.org/10.2147/OTT.S145708
Merika EE, Syrigos KN, Saif MW (2012) Desmoplasia in pancreatic cancer. Can we fight it? Gastroenterol Res Pract 2012:1–10. https://doi.org/10.1155/2012/781765
Midha S, Chawla S, Garg PK (2016) Modifiable and non-modifiable risk factors for pancreatic cancer: a review. Cancer Lett 381(1):269–277. https://doi.org/10.1016/j.canlet.2016.07.022
Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, Peterson A, Noteboom J, O’Briant KC, Allen A, Lin DW, Urban N, Drescher CW, Knudsen BS, Stirewalt DL, Gentleman R, Vessella RL, Nelson PS, Martin DB, Tewari M (2008) Circulating microRNAs as stable blood-based markers for cancer detection. Proc Nat Acad Sci 105(30):10513–10518. https://doi.org/10.1073/pnas.0804549105
Mitsuhashi K, Nosho K, Sukawa Y, Matsunaga Y, Ito M, Kurihara H, Kanno S, Igarashi H, Naito T, Adachi Y, Tachibana M, Tanuma T, Maguchi H, Shinohara T, Hasegawa T, Imamura M, Kimura Y, Hirata K, Maruyama R, Suzuki H, Imai K, Yamamoto H, Shinomura Y (2015) Association of Fusobacterium species in pancreatic cancer tissues with molecular features and prognosis. Oncotarget 6(9):7209–7220. https://doi.org/10.18632/oncotarget.3109
Montemagno C, Cassim S, De Leiris N, Durivault J, Faraggi M, Pagès G (2021) Pancreatic ductal adenocarcinoma: the dawn of the era of nuclear medicine? Int J Mol Sci 22(12):6413. https://doi.org/10.3390/ijms22126413
Moshiri F, Salvi A, Gramantieri L, Sangiovanni A, Guerriero P, De Petro G, Bassi C, Lupini L, Sattari A, Cheung D, Veneziano D, Nigita G, Shankaraiah RC, Portolani N, Carcoforo P, Fornari F, Bolondi L, Frassoldati A, Sabbioni S, Colombo M, Croce CM, Negrini M (2018) Circulating miR-106b-3p, mir-101-3p and miR-1246 as diagnostic biomarkers of hepatocellular carcinoma. Oncotarget 9(20):15350–15364. https://doi.org/10.18632/oncotarget.24601
Nejman D, Livyatan I, Fuks G, Gavert N, Zwang Y, Geller LT, Rotter-Maskowitz A, Weiser R, Mallel G, Gigi E, Meltser A, Douglas GM, Kamer I, Gopalakrishnan V, Dadosh T, Levin-Zaidman S, Avnet S, Atlan T, Cooper ZA, Arora R, Cogdill AP, Khan MAW, Ologun G, Bussi Y, Weinberger A, Lotan-Pompan M, Golani O, Perry G, Rokah M, Bahar-Shany K, Rozeman EA, Blank CU, Ronai A, Shaoul R, Amit A, Dorfman T, Kremer R, Cohen ZR, Harnof S, Siegal T, Yehuda-Shnaidman E, Gal-Yam EN, Shapira H, Baldini N, Langille MGI, Ben-Nun A, Kaufman B, Nissan A, Golan T, Dadiani M, Levanon K, Bar J, Yust-Katz S, Barshack I, Peeper DS, Raz DJ, Segal E, Wargo JA, Sandbank J, Shental N, Straussman R (2020) The human tumor microbiome is composed of tumor type–specific intracellular bacteria. Science (1979) 368(6494):973–980. https://doi.org/10.1126/science.aay9189
O’Neill RS, Stoita A (2021) Biomarkers in the diagnosis of pancreatic cancer: are we closer to finding the golden ticket? World J Gastroenterol 27(26):4045–4087. https://doi.org/10.3748/wjg.v27.i26.4045
Olson SH, Satagopan J, Xu Y, Ling L, Leong S, Orlow I, Saldia A, Li P, Nunes P, Madonia V, Allen PJ, O’Reilly E, Pamer E, Kurtz RC (2017) The oral microbiota in patients with pancreatic cancer, patients with IPMNs, and controls: a pilot study. Cancer Causes Control 28(9):959–969. https://doi.org/10.1007/s10552-017-0933-8
Pan P, Zhu Z, Oshima K, Aldakkak M, Tsai S, Huang Y, Dong W, Zhang J, Lin C, Wang Y, Yearsley M, Yu J, Wang L (2020) Black raspberries suppress pancreatic cancer through modulation of NKp46 +, CD8 +, and CD11b + immune cells. Food Front 1(1):70–82. https://doi.org/10.1002/fft2.1
Panebianco C, Villani A, Pazienza V (2019) High levels of prebiotic resistant starch in diet modulate gene expression and metabolomic profile in pancreatic cancer xenograft mice. Nutrients 11(4):709. https://doi.org/10.3390/nu11040709
Panebianco C, Villani A, Pisati F, Orsenigo F, Ulaszewska M, Latiano TP, Potenza A, Andolfo A, Terracciano F, Tripodo C, Perri F, Pazienza V (2022) Butyrate, a postbiotic of intestinal bacteria, affects pancreatic cancer and gemcitabine response in in vitro and in vivo models. Biomed Pharmacother 151:113163. https://doi.org/10.1016/j.biopha.2022.113163
Pansy K, Uhl B, Krstic J, Szmyra M, Fechter K, Santiso A, Thüminger L, Greinix H, Kargl J, Prochazka K, Feichtinger J, Deutsch AJA (2021) Immune regulatory processes of the tumor microenvironment under malignant conditions. Int J Mol Sci 22(24):13311. https://doi.org/10.3390/ijms222413311
Papa V, Schepis T, Coppola G, Chiappetta MF, Del Vecchio LE, Rozera T, Quero G, Gasbarrini A, Alfieri S, Papa A (2023) The role of microbiota in pancreatic cancer. Cancers 15(12):3143. https://doi.org/10.3390/cancers15123143
Papazoglou D, Papatheodorou K, Papanas N, Papadopoulos T, Gioka T, Kabouromiti G, Kotsiou S, Maltezos E (2010) Matrix metalloproteinase-1 and tissue inhibitor of metalloproteinases-1 levels in severely obese patients: what is the effect of weight loss? Exp Clin Endocrinol Diabetes 118(10):730–734. https://doi.org/10.1055/s-0030-1249671
Park J, Kim M, Kang SG, Jannasch AH, Cooper B, Patterson J 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.2014.44
Paternoster S, Falasca M (2020) The intricate relationship between diabetes, obesity and pancreatic cancer. Biochim Biophys Acta Rev Cancer 1873(1):188326. https://doi.org/10.1016/j.bbcan.2019.188326
Pfisterer N, Lingens C, Heuer C, Dang L, Neesse A, Ammer-Herrmenau C (2022) The microbiome in PDAC—vantage point for future therapies? Cancers (Basel) 14(23):5974. https://doi.org/10.3390/cancers14235974
Pourali G, Kazemi D, Chadeganipour AS, Arastonejad M, Kashani SN, Pourali R, Maftooh M, Akbarzade H, Fiuji H, Hassanian SM, Ghayour-Mobarhan M, Ferns GA, Khazaei M, Avan A (2024) Microbiome as a biomarker and therapeutic target in pancreatic cancer. BMC Microbiol 24(1):16. https://doi.org/10.1186/s12866-023-03166-4
Prokopchuk O, Grünwald B, Nitsche U, Jäger C, Prokopchuk OL, Schubert EC, Friess H, Martignoni ME, Krüger A (2018) Elevated systemic levels of the matrix metalloproteinase inhibitor TIMP-1 correlate with clinical markers of cachexia in patients with chronic pancreatitis and pancreatic cancer. BMC Cancer 18(1):128. https://doi.org/10.1186/s12885-018-4055-9
Pushalkar S, Hundeyin M, Daley D, Zambirinis CP, Kurz E, Mishra A, Mohan N, Aykut B, Usyk M, Torres LE, Werba G, Zhang K, Guo Y, Li Q, Akkad N, Lall S, Wadowski B, Gutierrez J, Kochen Rossi JA, Herzog JW, Diskin B, Torres-Hernandez A, Leinwand J, Wang W, Taunk PS, Savadkar S, Janal M, Saxena A, Li X, Cohen D, Sartor RB, Saxena D, Miller G (2018) The pancreatic cancer microbiome promotes oncogenesis by induction of innate and adaptive immune suppression. Cancer Discov 8(4):403–416. https://doi.org/10.1158/2159-8290.CD-17-1134
Rahman RA, Lamarca A, Hubner RA, Valle JW, McNamara MG (2021) The microbiome as a potential target for therapeutic manipulation in pancreatic cancer. Cancers (Basel) 13. https://doi.org/10.3390/cancers13153779
Ram P, Iyengar R (2001) G protein coupled receptor signaling through the Src and Stat3 pathway: role in proliferation and transformation. Oncogene 20:1601–1606
Ratajczak W, Rył A, Mizerski A, Walczakiewicz K, Sipak O, Laszczyńska M (2019) Immunomodulatory potential of gut microbiome-derived short-chain fatty acids (SCFAs). https://doi.org/10.18388/abp.2018_2648. Acta Biochim Pol
Riquelme E, Zhang Y, Zhang L, Montiel M, Zoltan M, Dong W, Quesada P, Sahin I, Chandra V, San Lucas A, Scheet P, Xu H, Hanash SM, Feng L, Burks JK, Do K-A, Peterson CB, Nejman D, Tzeng C-WD, Kim MP, Sears CL, Ajami N, Petrosino J, Wood LD, Maitra A, Straussman R, Katz M, White JR, Jenq R, Wargo J, McAllister F (2019) Tumor microbiome diversity and composition influence pancreatic cancer outcomes. Cell 178(4):795–806e12. https://doi.org/10.1016/j.cell.2019.07.008
Sanaei M, Kavoosi F (2022) Effect of sodium butyrate on p16INK4a, p14ARF, p15INK4b, class I HDACs (HDACs 1, 2, 3) class II HDACs (HDACs 4, 5, 6), cell growth inhibition and apoptosis induction in pancreatic cancer AsPC-1 and colon cancer HCT-116 cell lines. Asian Pac J Cancer Prev 23(3):795–802. https://doi.org/10.31557/APJCP.2022.23.3.795
Sethi V, Kurtom S, Tarique M, Lavania S, Malchiodi Z, Hellmund L, Zhang L, Sharma U, Giri B, Garg B, Ferrantella A, Vickers SM, Banerjee S, Dawra R, Roy S, Ramakrishnan S, Saluja A, Dudeja V (2018) Gut microbiota promotes tumor growth in mice by modulating immune response. Gastroenterology 155(1):33–37e6. https://doi.org/10.1053/j.gastro.2018.04.001
Sexton RE, Uddin MH, Bannoura S, Khan HY, Mzannar Y, Li Y, Aboukameel A, Al-Hallak MN, Al-Share B, Mohamed A, Nagasaka M, El-Rayes B, Azmi AS (2022) Connecting the human microbiome and pancreatic cancer. Cancer Metastasis Rev 41(2):317–331. https://doi.org/10.1007/s10555-022-10022-w
Seyhan AA (2023) Circulating microRNAs as potential biomarkers in pancreatic Cancer—advances and challenges. Int J Mol Sci 24(17):13340. https://doi.org/10.3390/ijms241713340
Siegel P, Massagué J (2003) Cytostatic and apoptotic actions of TGF-β in homeostasis and cancer. Nat Rev Cancer 3:807–820
Singh V, Lee G, Son H, Koh H, Kim ES, Unno T, Shin JH (2023) Butyrate producers, the sentinel of gut: their intestinal significance with and beyond butyrate, and prospective use as microbial therapeutics. Front Microbiol 13:1103836. https://doi.org/10.3389/fmicb.2022.1103836
Sobocki BK, Kaźmierczak-Siedlecka K, Folwarski M, Hawryłkowicz V, Makarewicz W, Stachowska E (2021) Pancreatic cancer and gut microbiome-related aspects: a comprehensive review and dietary recommendations. Nutrients 13(12):4425. https://doi.org/10.3390/nu13124425
Son M-Y, Cho H-S (2023) Anticancer effects of gut microbiota-derived short-chain fatty acids in cancers. J Microbiol Biotechnol 33(7):849–856. https://doi.org/10.4014/jmb.2301.01031
Staal B, Liu Y, Barnett D, Hsueh P, He Z, Gao C, Partyka K, Hurd MW, Singhi AD, Drake RR, Huang Y, Maitra A, Brand RE, Haab BB (2019) The sTRA plasma biomarker: blinded validation of improved accuracy over ca19-9 in pancreatic cancer diagnosis. Clin Cancer Res 25(9):2745–2754. https://doi.org/10.1158/1078-0432.CCR-18-3310
Stoffel EM, Brand RE, Goggins M (2023) Pancreatic cancer: changing epidemiology and new approaches to risk assessment, early detection, and prevention. Gastroenterology 164(5):752–765. https://doi.org/10.1053/j.gastro.2023.02.012
Takasaki H, Uchida E, Tempero MA, Burnett DA, Metzgar RS, Pour PM (1988) Correlative study on expression of CA 19 – 9 and DU-PAN-2 in tumor tissue and in serum of pancreatic cancer patients. Cancer Res 48(6):1435–1438
Tan Q, Ma X, Yang B, Liu Y, Xie Y, Wang X, Yuan W, Ma J (2022) Periodontitis pathogen Porphyromonas gingivalis promotes pancreatic tumorigenesis via neutrophil elastase from tumor-associated neutrophils. Gut Microbes 14(1). https://doi.org/10.1080/19490976.2022.2073785
Tarasiuk A, Mackiewicz T, Małecka-Panas E, Fichna J (2021) Biomarkers for early detection of pancreatic cancer - miRNAs as a potential diagnostic and therapeutic tool? Cancer Biol Ther 22(5–6):347–356. https://doi.org/10.1080/15384047.2021.1941584
Temel HY, Kaymak Ö, Kaplan S, Bahcivanci B, Gkoutos GV, Acharjee A (2023) Role of microbiota and microbiota-derived short‐chain fatty acids in < scp > PDAC. Cancer Med 12(5):5661–5675. https://doi.org/10.1002/cam4.5323
Tijeras-Raballand A, Hilmi M, Astorgues-Xerri L, Nicolle R, Bièche I, Neuzillet C (2021) Microbiome and pancreatic ductal adenocarcinoma. Clin Res Hepatol Gastroenterol 45(2):101589. https://doi.org/10.1016/j.clinre.2020.101589
Toni G (2021) What are postbiotics?
Torres PJ, Fletcher EM, Gibbons SM, Bouvet M, Doran KS, Kelley ST (2015) Characterization of the salivary microbiome in patients with pancreatic cancer. PeerJ 3:e1373. https://doi.org/10.7717/peerj.1373
van den Berg FF, van Dalen D, Hyoju SK, van Santvoort HC, Besselink MG, Wiersinga WJ, Zaborina O, Boermeester MA, Alverdy J (2021) Western-type diet influences mortality from necrotising pancreatitis and demonstrates a central role for butyrate. Gut 70(5):915–927. https://doi.org/10.1136/gutjnl-2019-320430
Vital M, Howe AC, Tiedje JM (2014) Revealing the bacterial butyrate synthesis pathways by analyzing (Meta)genomic data. mBio 5(2). https://doi.org/10.1128/mBio.00889-14
Wang X, Wang L, Mo Q, Dong Y, Wang G, Ji A (2015) Changes of Th17/Treg cell and related cytokines in pancreatic cancer patients. Int J Clin Exp Pathol 8(5):5702–5708
Wang Y, Yuan J-M, Pan A, Koh W-P (2020) Tissue inhibitor matrix metalloproteinase 1 and risk of type 2 diabetes in a Chinese population. BMJ Open Diabetes Res Care 8(1):e001051. https://doi.org/10.1136/bmjdrc-2019-001051
Xie Z, Yin X, Gong B, Nie W, Wu B, Zhang X, Huang J, Zhang P, Zhou Z, Li Z (2015) Salivary microRNAs show potential as a noninvasive biomarker for detecting resectable pancreatic cancer. Cancer Prev Res 8(2):165–173. https://doi.org/10.1158/1940-6207.CAPR-14-0192
Xie Z-B, Zhang Y-F, Jin C, Mao Y-S, Fu D-L (2019) LRG-1 promotes pancreatic cancer growth and metastasis via modulation of the EGFR/p38 signaling. J Exp Clin Cancer Res 38(1):75. https://doi.org/10.1186/s13046-019-1088-0
Xing H, Wang J, Wang Y, Tong M, Hu H, Huang C, Li D (2018) diagnostic value of CA 19 – 9 and carcinoembryonic antigen for pancreatic cancer: a meta-analysis. Gastroenterol Res Pract. 2018:1–9. https://doi.org/10.1155/2018/8704751
Xu Q, Briggs J, Park S (2005) Targeting Stat3 blocks both HIF-1 and VEGF expression induced by multiple oncogenic growth signaling pathways. Oncogene 24:5552–5560
Xu W, Wang Z, Zhang W, Qian K, Li H, Kong D et al (2015) Mutated K-ras activates CDK8 to stimulate the epithelial-to-mesenchymal transition in pancreatic cancer in part via the Wnt/β-catenin signaling pathway. Cancer Lett 356:613–627. https://doi.org/10.1016/j.canlet.2014.10.008
Yachida S, Jones S, Bozic I, Antal T, Leary R, Fu B, Kamiyama M, Hruban RH, Eshleman JR, Nowak MA, Velculescu VE, Kinzler KW, Vogelstein B, Iacobuzio-Donahue CA (2010) Distant metastasis occurs late during the genetic evolution of pancreatic cancer. Nature 467(7319):1114–1117. https://doi.org/10.1038/nature09515
Yang M, Zhang C-Y (2021) Diagnostic biomarkers for pancreatic cancer: an update. World J Gastroenterol 27(45):7862–7865. https://doi.org/10.3748/wjg.v27.i45.7862
Yang J-Y, Sun Y-W, Liu D-J, Zhang J-F, Li J, Hua R (2014) MicroRNAs in stool samples as potential screening biomarkers for pancreatic ductal adenocarcinoma cancer. Am J Cancer Res 4(6):663–673
Yang W, Yu T, Huang X, Bilotta AJ, Xu L, Lu Y, Sun J, Pan F, Zhou J, Zhang W, Yao S, Maynard CL, Singh N, Dann SM, Liu Z, Cong Y (2020) Intestinal microbiota-derived short-chain fatty acids regulation of immune cell IL-22 production and gut immunity. Nat Commun 11(1):4457. https://doi.org/10.1038/s41467-020-18262-6
Yu DCW, Waby JS, Chirakkal H, Staton CA, Corfe BM (2010) Butyrate suppresses expression of neuropilin I in colorectal cell lines through inhibition of Sp1 transactivation. Mol Cancer 9. https://doi.org/10.1186/1476-4598-9-276
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/s41564-019-0649-5
Zambirinis CP, Pushalkar S, Saxena D, Miller G (2014) Pancreatic cancer, inflammation, and microbiome. Cancer J 20(3):195–202. https://doi.org/10.1097/PPO.0000000000000045
Zhang L, Farrell JJ, Zhou H, Elashoff D, Akin D, Park N, Chia D, Wong DT (2010) Salivary transcriptomic biomarkers for detection of resectable pancreatic cancer. Gastroenterology 138(3):949–957e7. https://doi.org/10.1053/j.gastro.2009.11.010
Zhang P, Zou M, Wen X, Gu F, Li J, Liu G, Dong J, Deng X, Gao J, Li X, Jia X, Dong Z, Chen L, Wang Y, Tian Y (2014) Development of serum parameters panels for the early detection of pancreatic cancer. Int J Cancer 134(11):2646–2655. https://doi.org/10.1002/ijc.28584
Zhang L, Sanagapalli S, Stoita A (2018) Challenges in diagnosis of pancreatic cancer. World J Gastroenterol 24(19):2047–2060. https://doi.org/10.3748/wjg.v24.i19.2047
Zhang J, Wang Y, Zhao T, Li Y, Tian L, Zhao J, Zhang J (2020a) Evaluation of serum MUC5AC in combination with CA19-9 for the diagnosis of pancreatic cancer. World J Surg Oncol 18(1):31. https://doi.org/10.1186/s12957-020-1809-z
Zhang M, Huang L, Ding G, Huang H, Cao G, Sun X, Lou N, Wei Q, Shen T, Xu X, Cao L, Yan Q (2020b) Interferon gamma inhibits CXCL8–CXCR2 axis mediated tumor-associated macrophages tumor trafficking and enhances anti-PD1 efficacy in pancreatic cancer. J Immunother Cancer 8(1):e000308. https://doi.org/10.1136/jitc-2019-000308
Zhang K, Cai J, Lu C, Zhu Q, Zhan C, Shen Y, Gu J, Ge D (2021) Tumor size as a predictor for prognosis of patients with surgical IIIA-N2 non-small cell lung cancer after surgery. J Thorac Dis 13(7):4114–4124. https://doi.org/10.21037/jtd-21-428
Zhang K, Su A, Wang X, Zhao W, He L, Wei T, Li Z, Zhu J, Chen YW (2022) Non-linear correlation between tumor size and survival outcomes for parathyroid carcinoma: a SEER population-based cohort study. Front Endocrinol (Lausanne) 13:882579. https://doi.org/10.3389/fendo.2022.882579
Zhou W, Zhang D, Li Z, Jiang H, Li J, Ren R, Gao X, Li J, Wang X, Wang W, Yang Y (2021a) The fecal microbiota of patients with pancreatic ductal adenocarcinoma and autoimmune pancreatitis characterized by metagenomic sequencing. J Transl Med 19(1):215. https://doi.org/10.1186/s12967-021-02882-7
Zhou Y, Ji X, Chen J, Fu Y, Huang J, Guo R, Zhou J, Cen J, Zhang Q, Chu A, Huang Y, Xu C, Wang F (2021b) Shortchain fatty acid butyrate: a novel shield against chronic gastric ulcer. Exp Ther Med 21(4):329. https://doi.org/10.3892/etm.2021.9760
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Elango, A., Nesam, V.D., Sukumar, P. et al. Postbiotic butyrate: role and its effects for being a potential drug and biomarker to pancreatic cancer. Arch Microbiol 206, 156 (2024). https://doi.org/10.1007/s00203-024-03914-8
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DOI: https://doi.org/10.1007/s00203-024-03914-8