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Diet and gut microbiome interactions in gynecologic cancer

Published:September 12, 2020DOI:https://doi.org/10.1016/j.ygyno.2020.08.027

      Highlights

      • The gut microbiome is influenced by multiple factors including diet and lifestyle.
      • The gut microbiome plays an important role in carcinogenesis and immune system regulation.
      • Obesity, estrogen and inflammation modify the gut microbiome and impact gynecologic cancers.
      • Response to chemotherapy and immunotherapy is influenced by the gut microbiome.
      • Dietary interventions may modulate the gut microbiome and tumor microenvironment.

      Abstract

      Over the last decade, there has been a dramatic surge in research exploring the human gut microbiome and its role in health and disease. It is now widely accepted that commensal microorganisms coexist within the human gastrointestinal tract and other organs, including those of the reproductive tract. These microorganisms, which are collectively known as the “microbiome”, contribute to maintaining host physiology and to the development of pathology. Next generation sequencing and multi-‘omics’ technology has enriched our understanding of the complex and interdependent relationship that exists between the host and microbiome. Global changes in the microbiome are known to be influenced by dietary, genetic, lifestyle, and environmental factors. Accumulating data have shown that alterations in the gut microbiome contribute to the development, prognosis and treatment of many disease states including cancer primarily through interactions with the immune system. However, there are large gaps in knowledge regarding the association between the gut microbiome and gynecologic cancers, and research characterizing the reproductive tract microbiome is insufficient. Herein, we explore the mechanisms by which alterations in the gut and reproductive tract microbiome contribute to carcinogenesis focusing on obesity, hyperestrogenism, inflammation and altered tumor metabolism. The impact of the gut microbiome on response to anti-cancer therapy is highlighted with an emphasis on immune checkpoint inhibitor efficacy in gynecologic cancers. We discuss dietary interventions that are likely to modulate the metabolic and immunologic milieu as well as tumor microenvironment through the gut microbiome including intermittent fasting/ketogenic diet, high fiber diet, use of probiotics and the metabolic management of obesity. We conclude that enhanced understanding of the microbiome in gynecologic cancers coupled with thorough evaluation of metabolic and metagenomic analyses would enable us to integrate novel preventative strategies and adjunctive interventions into the care of women with gynecologic cancers.

      Keywords

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      References

        • Bultman S.J.
        The microbiome and its potential as a cancer preventive intervention.
        Semin. Oncol. 2016 Feb; 43 ([Internet]. Available from:): 97-106
        • Scott A.J.
        • Alexander J.L.
        • Merrifield C.A.
        • Cunningham D.
        • Jobin C.
        • Brown R.
        • et al.
        International cancer microbiome consortium consensus statement on the role of the human microbiome in carcinogenesis.
        Gut. 2019 Sep; 68 ([Internet]. Available from:): 1624-1632
        • Defazio J.
        • Fleming I.D.
        • Shakhsheer B.
        • Zaborina O.
        • Alverdy J.C.
        The opposing forces of the intestinal microbiome and the emerging pathobiome.
        Surg. Clin. North Am. 2014 Dec; 94 ([Internet]. Available from:): 1151-1161
        • Soldati L.
        • Di Renzo L.
        • Jirillo E.
        • Ascierto P.A.
        • Marincola F.M.
        • De Lorenzo A.
        The influence of diet on anti-cancer immune responsiveness.
        J. Transl. Med. 2018; 16 ([Internet]. Available from:): 1-18
        • Singh R.K.
        • Chang H.-W.
        • Yan D.
        • Lee K.M.
        • Ucmak D.
        • Wong K.
        • et al.
        Influence of diet on the gut microbiome and implications for human health.
        J. Transl. Med. 2017 Dec 8; 15 ([Internet]. Available from:): 73
        • Chase D.
        • Goulder A.
        • Zenhausern F.
        • Monk B.
        • Herbst-Kralovetz M.
        The vaginal and gastrointestinal microbiomes in gynecologic cancers: a review of applications in etiology, symptoms and treatment.
        Gynecol. Oncol. 2015 Jul; 138 ([Internet]. Available from:): 190-200
        • Muls A.
        • Andreyev J.
        • Lalondrelle S.
        • Taylor A.
        • Norton C.
        • Hart A.
        Systematic review: the impact of cancer treatment on the gut and vaginal microbiome in women with a gynecological malignancy.
        Int. J. Gynecol. Cancer. 2017; 27 ([Internet]. Available from): 1550-1559
        • Mert I.
        • Walther-Antonio M.
        • Mariani A.
        Case for a role of the microbiome in gynecologic cancers: clinician’s perspective.
        J. Obstet. Gynaecol. Res. 2018 Sep; 44 ([Internet]. Available from:): 1693-1704
        • Belizário J.E.
        • Faintuch J.
        Microbiome and gut dysbiosis.
        in: Experientia supplementum (2012). 2018: 459-476 ([Internet]. Available from:)
        • Helmink B.A.
        • Khan M.A.W.
        • Hermann A.
        • Gopalakrishnan V.
        • Wargo J.A.
        The microbiome, cancer, and cancer therapy.
        Nat. Med. 2019 Mar 6; 25 ([Internet]. Available from:): 377-388
        • Mani S.
        Microbiota and breast cancer.
        in: Progress in Molecular Biology and Translational Science. 2017: 217-229 ([Internet]. Available from:)
        • Armougom F.
        • Raoult D.
        Use of pyrosequencing and DNA barcodes to monitor variations in firmicutes and bacteroidetes communities in the gut microbiota of obese humans.
        BMC Genomics. 2008; 9 ([Internet]. Available from:): 576
        • O’Keefe S.J.D.
        Diet, microorganisms and their metabolites, and colon cancer.
        Nat. Rev. Gastroenterol. Hepatol. 2016 Dec 16; 13 ([Internet]. Available from:): 691-706
        • Leonardi G.C.
        • Accardi G.
        • Monastero R.
        • Nicoletti F.
        • Libra M.
        Ageing: from inflammation to cancer.
        Immun. Ageing. 2018; 15: 1-7
        • Farhana L.
        • Banerjee H.N.
        • Verma M.
        • Majumdar A.P.N.
        Role of microbiome in carcinogenesis process and epigenetic regulation of colorectal cancer.
        in: Methods in Molecular Biology. 2018: 35-55 ([Internet]. Available from:)
        • Chen L.
        • Zhang Y.-H.
        • Huang T.
        • Cai Y.-D.
        Gene expression profiling gut microbiota in different races of humans.
        Sci. Rep. 2016 Sep 15; 6 ([Internet]. Available from:): 23075
        • Royston K.J.
        • Adedokun B.
        • Olopade O.I.
        Race, the microbiome and colorectal cancer.
        World J. Gastrointest. Oncol. 2019 Oct 15; 11 ([Internet]. Available from:): 773-787
        • Bhatt A.P.
        • Redinbo M.R.
        • Bultman S.J.
        The role of the microbiome in cancer development and therapy.
        CA Cancer J. Clin. 2017 Jul 8; 67 ([Internet]. Available from:): 326-344
        • Helmink B.A.
        • Khan M.A.W.
        • Hermann A.
        • Gopalakrishnan V.
        • Wargo J.A.
        The microbiome, cancer, and cancer therapy.
        Nat. Med. 2019 Mar; 25: 377-388
        • Scott A.J.
        • Alexander J.L.
        • Merrifield C.A.
        • Cunningham D.
        • Jobin C.
        • Brown R.
        • et al.
        International Cancer Microbiome Consortium consensus statement on the role of the human microbiome in carcinogenesis.
        Gut. 2019 Sep; 68: 1624-1632
        • Bultman S.J.
        Interplay between diet, gut microbiota, epigenetic events, and colorectal cancer.
        Mol. Nutr. Food Res. 2017 Jan; 61 ([Internet]. Available from:): 1500902
        • Gentile C.L.
        • Weir T.L.
        The gut microbiota at the intersection of diet and human health.
        Science (80). 2018 Nov 16; 362 ([Internet]. Available from:): 776-780
        • Górska A.
        • Przystupski D.
        • Niemczura M.J.
        • Kulbacka J.
        Probiotic bacteria: a promising tool in cancer prevention and therapy.
        Curr. Microbiol. 2019 Aug 4; 76 ([Internet]. Available from:): 939-949
        • Baker J.M.
        • Al-Nakkash L.
        • Herbst-Kralovetz M.M.
        Estrogen–gut microbiome axis: physiological and clinical implications.
        Maturitas. 2017; 103 ([Internet]. Available from:): 45-53
        • Champer M.
        • Wong A.M.
        • Champer J.
        • Brito I.L.
        • Messer P.W.
        • Hou J.Y.
        • et al.
        The role of the vaginal microbiome in gynaecological cancer.
        BJOG. 2018; 125 ([Internet]. Available from): 309-315
        • Schwabe R.F.
        • Jobin C.
        The microbiome and cancer.
        Nat. Rev. Cancer. 2013 Nov 17; 13 ([Internet]. Available from:): 800-812
        • Clements S.J.
        • R. Carding S.
        Diet, the intestinal microbiota, and immune health in aging.
        Crit. Rev. Food Sci. Nutr. 2018 Mar 4; 58 ([Internet]. Available from:): 651-661
        • Mehta R.S.
        • Nishihara R.
        • Cao Y.
        • Song M.
        • Mima K.
        • Qian Z.R.
        • et al.
        Association of dietary patterns with risk of colorectal cancer subtypes classified by fusobacterium nucleatum in tumor tissue.
        JAMA Oncol. 2017 Jul 1; 3 ([Internet]. Available from:): 921
        • Cogdill A.P.
        • Gaudreau P.O.
        • Arora R.
        • Gopalakrishnan V.
        • Wargo J.A.
        The impact of Intratumoral and gastrointestinal microbiota on systemic cancer therapy.
        Trends Immunol. 2018 Nov; 39 ([Internet]. Available from:): 900-920
        • Hills R.D.
        • Pontefract B.A.
        • Mishcon H.R.
        • Black C.A.
        • Sutton S.C.
        • Theberge C.R.
        Gut microbiome: profound implications for diet and disease.
        Nutrients. 2019 Jul 16; 11 ([Internet]. Available from:): 1613
        • Mitra A.
        • MacIntyre D.A.
        • Marchesi J.R.
        • Lee Y.S.
        • Bennett P.R.
        • Kyrgiou M.
        The vaginal microbiota, human papillomavirus infection and cervical intraepithelial neoplasia: what do we know and where are we going next?.
        Microbiome. 2016; 4 ([Internet]. Available from): 58
        • Wong A.
        • Maclean A.B.
        • Furrows S.J.
        • Ridgway G.L.
        • Hardiman P.J.
        • Perrett C.W.
        Could epithelial ovarian cancer be associated with chlamydial infection?.
        Eur. J. Gynaecol. Oncol. 2007; 28 ([Internet]. Available from): 117-120
        • Zhou B.
        • Sun C.
        • Huang J.
        • Xia M.
        • Guo E.
        • Li N.
        • et al.
        The biodiversity composition of microbiome in ovarian carcinoma patients.
        Sci. Rep. 2019 Dec 8; 9 ([Internet]. Available from:): 1691
        • Walther-António M.R.S.
        • Chen J.
        • Multinu F.
        • Hokenstad A.
        • Distad T.J.
        • Cheek E.H.
        • et al.
        Potential contribution of the uterine microbiome in the development of endometrial cancer.
        Genome. Med. 2016 Dec 25; 8 ([Internet]. Available from:): 122
        • Yang T.-K.
        • Chung C.-J.
        • Chung S.-D.
        • Muo C.-H.
        • Chang C.-H.
        • Huang C.-Y.
        Risk of endometrial cancer in women with pelvic inflammatory disease: a nationwide population-based retrospective cohort study.
        Medicine (Baltimore). 2015 Aug; 94 ([Internet]. Available from): e1278
        • Rowlands I.J.
        • Nagle C.M.
        • Spurdle A.B.
        • Webb P.M.
        • Australian National Endometrial Cancer Study Group
        • Australian Ovarian Cancer Study Group
        Gynecological conditions and the risk of endometrial cancer.
        Gynecol. Oncol. 2011 Dec; 123 ([Internet]. Available from): 537-541
        • Walsh D.M.
        • Hokenstad A.N.
        • Chen J.
        • Sung J.
        • Jenkins G.D.
        • Chia N.
        • et al.
        Postmenopause as a key factor in the composition of the endometrial cancer microbiome (ECbiome).
        Sci. Rep. 2019 Dec 16; 9 ([Internet]. Available from:): 19213
        • Fuhrman B.J.
        • Feigelson H.S.
        • Flores R.
        • Gail M.H.
        • Xu X.
        • Ravel J.
        • et al.
        Associations of the fecal microbiome with urinary estrogens and estrogen metabolites in postmenopausal women.
        J. Clin. Endocrinol. Metab. 2014 Dec; 99 ([Internet]. Available from): 4632-4640
        • Flores R.
        • Shi J.
        • Fuhrman B.
        • Xu X.
        • Veenstra T.D.
        • Gail M.H.
        • et al.
        Fecal microbial determinants of fecal and systemic estrogens and estrogen metabolites: a cross-sectional study.
        J. Transl. Med. 2012 Dec 21; 10 ([Internet]. Available from): 253
        • Goedert J.J.
        • Jones G.
        • Hua X.
        • Xu X.
        • Yu G.
        • Flores R.
        • et al.
        Investigation of the association between the fecal microbiota and breast cancer in postmenopausal women: a population-based case-control pilot study.
        JNCI J. Natl. Cancer Inst. 2015 Aug; 107 ([Internet]. Available from:)
        • Hawkins G.
        • McCoy N.
        • Su W.
        • Keku T.
        • Zhou C.
        • Brewster W.R.
        • Bae-Jump V.
        Impact of obesity on the uterine and gut microbiome in postmenopausal mice with and without endometrial cancer.
        51st Annu. Meet. Soc. Gynecol. Oncol. 2020; (March)
        • Hawkins G.
        • Clark L.H.
        • Sullivan S.
        • McCoy N.
        • Keki T.
        • Brewster W.B.
        • Bae-Jump V.
        Impact of ethnicity and obesity on the uterine microbiome in women and mice with endometrial cancer.
        in: 50th Annual Meeting of the Society of Gynecologic Oncology. 2019 (p. (March))
        • Icard P.
        • Shulman S.
        • Farhat D.
        • Steyaert J.
        • Alifano M.
        • Lyon U.
        • et al.
        How the warburg effect supports aggressiveness and drug resistance of cancer cells?.
        Drug Resist. Updat. 2018; 38 ([Internet]. Available from): 1-11
        • Seyfried T.N.
        • Sanderson T.M.
        • El-Abbadi M.M.
        • McGowan R.
        • Mukherjee P.
        Role of glucose and ketone bodies in the metabolic control of experimental brain cancer.
        Br. J. Cancer. 2003; 89: 1375-1382
        • Makowski L.
        • Zhou C.
        • Zhong Y.
        • Kuan P.F.
        • Fan C.
        • Sampey B.P.
        • et al.
        Obesity increases tumor aggressiveness in a genetically engineered mouse model of serous ovarian cancer.
        Gynecol. Oncol. 2014 Apr; 133: 90-97
        • Guo H.
        • Kong W.
        • Zhang L.
        • Han J.
        • Clark L.H.
        • Yin Y.
        • et al.
        Reversal of obesity-driven aggressiveness of endometrial cancer by metformin.
        Am. J. Cancer Res. 2019; 9 ([Internet]. Available from): 2170-2193
        • Wallace T.C.
        • Bultman S.
        • D’Adamo C.
        • Daniel C.R.
        • Debelius J.
        • Ho E.
        • et al.
        Personalized nutrition in disrupting cancer — proceedings from the 2017 American College of Nutrition Annual Meeting.
        J. Am. Coll. Nutr. 2019 Jan 2; 38 ([Internet]. Available from:): 1-14
        • Seyfried T.N.
        • Flores R.
        • Poff A.M.
        • D’Agostino D.P.
        • Mukherjee P.
        Metabolic therapy: a new paradigm for managing malignant brain cancer.
        Cancer Lett. 2015 Jan 28; 356 ([Internet]. Available from): 289-300
        • Oliveira C.L.P.
        • Mattingly S.
        • Schirrmacher R.
        • Sawyer M.B.
        • Fine E.J.
        • Prado C.M.
        A nutritional perspective of ketogenic diet in cancer: a narrative review.
        J. Acad. Nutr. Diet. 2018; 118 ([Internet]. Available from): 668-688
        • Klement R.J.
        • Pazienza V.
        Impact of different types of diet on gut microbiota profiles and cancer prevention and treatment.
        Med. 2019; 55: 1-10
        • Romero Iris L.
        • McCormick A.
        • McEwen K.A.
        • Park S.
        • Karrison T.
        • Yamada S.D.
        • et al.
        Relationship of type II diabetes and metformin use to ovarian cancer progression, survival, and chemosensitivity.
        Obstet. Gynecol. 2012 Jan; 119 ([Internet]. Available from): 61-67
        • Casati M.
        • Ferri E.
        • Azzolino D.
        • Cesari M.
        • Arosio B.
        Gut microbiota and physical frailty through the mediation of sarcopenia.
        Exp. Gerontol. 2019 Sep; 124 ([Internet]. Available from:): 110639
        • Ticinesi A.
        • Lauretani F.
        • Milani C.
        • Nouvenne A.
        • Tana C.
        • Del Rio D.
        • et al.
        Aging gut microbiota at the cross-road between nutrition, physical frailty, and sarcopenia: is there a gut–muscle axis?.
        Nutrients. 2017 Nov 30; 9 ([Internet]. Available from:): 1303
        • Leonardi G.C.
        • Accardi G.
        • Monastero R.
        • Nicoletti F.
        • Libra M.
        Ageing: from inflammation to cancer.
        Immun. Ageing. 2018 Dec 19; 15 ([Internet]. Available from:): 1
        • Ferrucci L.
        • Fabbri E.
        Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty.
        Nat. Rev. Cardiol. 2018 Sep; 15 ([Internet]. Available from:): 505-522
        • Ni Lochlainn M.
        • Bowyer R.
        • Steves C.
        Dietary protein and muscle in aging people: the potential role of the gut microbiome.
        Nutrients. 2018 Jul 20; 10 ([Internet]. Available from:): 929
        • Avgerinos K.I.
        • Spyrou N.
        • Mantzoros C.S.
        • Dalamaga M.
        Obesity and cancer risk: emerging biological mechanisms and perspectives.
        Metabolism. 2019; 92 ([Internet]. Available from): 121-135
        • Gately S.
        Human Microbiota and Personalized Cancer Treatments: Role of Commensal Microbes in Treatment Outcomes for Cancer Patients.
        (In)2019: 253-264 (Available from:)
        • Panebianco C.
        • Andriulli A.
        • Pazienza V.
        Pharmacomicrobiomics: exploiting the drug-microbiota interactions in anticancer therapies.
        Microbiome. 2018 Dec 22; 6 ([Internet]. Available from:): 92
        • Rea D.
        • Coppola G.
        • Palma G.
        • Barbieri A.
        • Luciano A.
        • Del Prete P.
        • et al.
        Microbiota effects on cancer: from risks to therapies.
        Oncotarget. 2018; 9: 17915-17927
        • Bhatt A.P.
        • Redinbo M.R.
        • Bultman S.J.
        The role of the microbiome in cancer development and therapy.
        CA Cancer J. Clin. 2017 Jul; 67: 326-344
        • Farhana L.
        • Banerjee H.N.
        • Verma M.
        Majumdar APN. Role of Microbiome in Carcinogenesis Process and Epigenetic Regulation of Colorectal Cancer.
        (In)2018: 35-55
        • Baiden-Amissah R.E.M.
        • Tuyaerts S.
        Contribution of aging, obesity, and microbiota on tumor immunotherapy efficacy and toxicity.
        Int. J. Mol. Sci. 2019 Jul 23; 20 ([Internet]. Available from:): 3586
        • Levinson K.
        • Dorigo O.
        • Rubin K.
        • Moore K.
        Immunotherapy in gynecologic cancers: what we know now and where we are headed.
        Am. Soc. Clin. Onco.l Educ. B. 2019 May; 39 ([Internet]. Available from:): e126-e140
        • Marinelli O.
        • Annibali D.
        • Aguzzi C.
        • Tuyaerts S.
        • Amant F.
        • Morelli M.B.
        • et al.
        The controversial role of PD-1 and its ligands in gynecological malignancies.
        Front. Oncol. 2019 Oct 15; 9 ([Internet]. Available from:)
        • Sipe L.M.
        • Chaib M.
        • Pingili A.K.
        • Pierre J.F.
        • Makowski L.
        Microbiome, bile acids, and obesity: how microbially modified metabolites shape anti-tumor immunity.
        Immunol. Rev. 2020 May 22; 295 ([Internet]. Available from:): 220-239
        • Naik G.S.
        • Waikar S.S.
        • Johnson A.E.W.
        • Buchbinder E.I.
        • Haq R.
        • Hodi F.S.
        • et al.
        Complex inter-relationship of body mass index, gender and serum creatinine on survival: exploring the obesity paradox in melanoma patients treated with checkpoint inhibition.
        J. Immunother. Cancer. 2019 Dec 29; 7 ([Internet]. Available from:): 89
        • Lettieri-Barbato D.
        • Aquilano K.
        Pushing the limits of cancer therapy: the nutrient game.
        Front. Oncol. 2018 May 8; 8 ([Internet]. Available from:)
        • İyikesici M.S.
        • Slocum A.K.
        • Slocum A.
        • Berkarda F.B.
        • Kalamian M.
        • Seyfried T.N.
        Efficacy of metabolically supported chemotherapy combined with ketogenic diet, hyperthermia, and hyperbaric oxygen therapy for stage IV triple-negative breast cancer.
        Cureus. 2017; 9: 1-14
        • Al-Wahab Z.
        • Tebbe C.
        • Chhina J.
        • Dar S.A.
        • Morris R.T.
        • Ali-Fehmi R.
        • et al.
        Dietary energy balance modulates ovarian cancer progression and metastasis.
        Oncotarget. 2014; 5: 6063-6075
        • Wright C.
        • Simone N.L.
        Obesity and tumor growth: inflammation, immunity, and the role of a ketogenic diet.
        Curr. Opin. Clin. Nutr. Metab. Care. 2016; 19 ([Internet]. Available from): 294-299
        • Cohen C.W.
        • Fontaine K.R.
        • Arend R.C.
        • Alvarez R.D.
        • Leath III, C.A.
        • Huh W.K.
        • et al.
        A ketogenic diet reduces central obesity and serum insulin in women with ovarian or endometrial cancer.
        J. Nutr. 2018 Aug 1; 148 ([Internet]. Available from:): 1253-1260
        • Allen B.G.
        • Bhatia S.K.
        • Anderson C.M.
        • Eichenberger-Gilmore J.M.
        • Sibenaller Z.A.
        • Mapuskar K.A.
        • et al.
        Ketogenic diets as an adjuvant cancer therapy: history and potential mechanism.
        Redox Biol. 2014; 2 ([Internet]. Available from): 963-970
        • Cohen C.W.
        • Fontaine K.R.
        • Arend R.C.
        • Gower B.A.
        A ketogenic diet is acceptable in women with ovarian and endometrial cancer and has no adverse effects on blood lipids: a randomized, controlled trial.
        Nutr. Cancer. 2020 May 18; 72 ([Internet]. Available from:): 584-594
        • Klement R.J.
        • Sweeney R.A.
        Impact of a ketogenic diet intervention during radiotherapy on body composition: II. Protocol of a randomised phase I study (KETOCOMP).
        Clin. Nutr. ESPEN. 2016; 12 ([Internet]. Available from): e1-e6
        • Allen B.G.
        • Bhatia S.K.
        • Buatti J.M.
        • Brandt K.E.
        • Lindholm K.E.
        • Button A.M.
        • et al.
        Ketogenic Diets Enhance Oxidative Stress and Radio- Chemo-Therapy Responses in Lung Cancer Xenografts.
        9. 2013: 3905-3914
        • Cohen C.W.
        • Fontaine K.R.
        • Arend R.C.
        • Soleymani T.
        • Gower B.A.
        Favorable effects of a ketogenic diet on physical function, perceived energy, and food cravings in women with ovarian or endometrial cancer: a randomized, controlled trial.
        Nutrients. 2018 Aug 30; 10 ([Internet]. Available from)
        • Chan C.W.H.
        • Law B.M.H.
        • Waye M.M.Y.
        • Chan J.Y.W.
        • So W.K.W.
        • Chow K.M.
        Trimethylamine-N-oxide as one hypothetical link for the relationship between intestinal microbiota and cancer–where we are and where shall we go?.
        J. Cancer. 2019; 10 ([Internet]. Available from:): 5874-5882
        • Roberts A.B.
        • Gu X.
        • Buffa J.A.
        • Hurd A.G.
        • Wang Z.
        • Zhu W.
        • et al.
        Development of a gut microbe–targeted nonlethal therapeutic to inhibit thrombosis potential.
        Nat. Med. 2018 Sep 6; 24 ([Internet]. Available from:): 1407-1417
        • Kolodziejczyk A.A.
        • Zheng D.
        • Elinav E.
        Diet–microbiota interactions and personalized nutrition.
        Nat. Rev. Microbiol. 2019 Dec 20; 17 ([Internet]. Available from:): 742-753