Variability in disease presentation, progression and treatment response has been a central challenge in medicine. Although variability in host factors and genetics are important, it has become evident that the gut microbiome, with its vast genetic and metabolic diversity, must be considered in moving towards individualized treatment. In this Review, we discuss six broad disease groups: infectious disease, cancer, metabolic disease, cardiovascular disease, autoimmune or inflammatory disease, and allergic and atopic diseases. We highlight current knowledge on the gut microbiome in disease pathogenesis and prognosis, efficacy, and treatment-related adverse events and its promise for stratifying existing treatments and as a source of novel therapies. The Review is not meant to be comprehensive for each disease state but rather highlights the potential implications of the microbiome as a tool to individualize treatment strategies in clinical practice. Although early, the outlook is optimistic but challenges need to be overcome before clinical implementation, including improved understanding of underlying mechanisms, longitudinal studies with multiple data layers reflecting gut microbiome and host response, standardized approaches to testing and reporting, and validation in larger cohorts. Given progress in the microbiome field with concurrent basic and clinical studies, the microbiome will likely become an integral part of clinical care within the next decade.
The gut microbiome, with substantially greater genetic diversity than the host, is an important factor in determining the variability in disease development, progression and treatment response.
Tremendous progress has been made in characterizing the microbiome and its influence on biology.
Stratifying to species or strain level is important as microorganisms within the same genus might have a differing effect on the same disease process; the same organism might also have different effects on separate disease processes, making the definition of a universal ‘healthy’ microbiota based on composition alone difficult.
To incorporate the microbiome in the clinic, large patient cohorts with multidimensional and longitudinal analyses are needed to understand the contribution of the microbiome on disease development, progression and treatment in the context of systems biology.
The gut microbiome is an important component in personalized medicine; most of the progress has been in metabolic and cardiovascular disorders as well as in cancer therapies.
The gut microbiome is influenced by numerous factors (including age, diet and host genetics) and hence serves as a readout for those factors, simplifying the input for machine learning-based models in clinical practice being developed to predict disease outcomes or treatment response.
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Kashyap, P. C., Chia, N., Nelson, H., Segal, E. & Elinav, E. Microbiome at the frontier of personalized medicine. Mayo Clin. Proc. 92, 1855–1864 (2017).
Jameson, J. L. & Longo, D. L. Precision medicine–personalized, problematic, and promising. N. Engl. J. Med. 372, 2229–2234 (2015).
Gilbert, J. A. et al. Current understanding of the human microbiome. Nat. Med. 24, 392–400 (2018).
Ejtahed, H. S., Hasani-Ranjbar, S. & Larijani, B. Human microbiome as an approach to personalized medicine. Altern. Ther. Health Med. 23, 8–9 (2017).
Zimmermann, M., Zimmermann-Kogadeeva, M., Wegmann, R. & Goodman, A. L. Mapping human microbiome drug metabolism by gut bacteria and their genes. Nature 570, 462–467 (2019).
Eckburg, P. B. et al. Diversity of the human intestinal microbial flora. Science 308, 1635–1638 (2005).
Schubert, A. M. et al. Microbiome data distinguish patients with Clostridium difficile infection and non-C. difficile-associated diarrhea from healthy controls. mBio 5, e01021-14 (2014).
Marchesi, J. R. et al. The gut microbiota and host health: a new clinical frontier. Gut 65, 330–339 (2016).
Vindigni, S. M. & Surawicz, C. M. Fecal microbiota transplantation. Gastroenterol. Clin. North. Am. 46, 171–185 (2017).
Hill, C. et al. Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat. Rev. Gastroenterol. Hepatol. 11, 506–514 (2014).
Gibson, G. R. et al. Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nat. Rev. Gastroenterol. Hepatol. 14, 491–502 (2017).
Swanson, K. S. et al. The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of synbiotics. Nat. Rev. Gastroenterol. Hepatol. 17, 687–701 (2020).
Cully, M. Microbiome therapeutics go small molecule. Nat. Rev. Drug. Discov. 18, 569–572 (2019).
Wong, A. C. & Levy, M. New approaches to microbiome-based therapies. mSystems 4, e00122-19 (2019).
Lessa, F. C. et al. Burden of Clostridium difficile infection in the United States. N. Engl. J. Med. 372, 825–834 (2015).
McDonald, L. C. et al. Clinical practice guidelines for clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin. Infect. Dis. 66, e1–e48 (2018).
Song, J. H. & Kim, Y. S. Recurrent Clostridium difficile infection: risk factors, treatment, and prevention. Gut Liver 13, 16–24 (2019).
Antharam, V, C. et al. Intestinal dysbiosis and depletion of butyrogenic bacteria in Clostridium difficile infection and nosocomial diarrhea. J. Clin. Microbiol. 51, 2884–2892 (2013).
Battaglioli, E. J. et al. Clostridioides difficile uses amino acids associated with gut microbial dysbiosis in a subset of patients with diarrhea. Sci Transl Med 10, eaam7019 (2018).
Ng, K. M. et al. Microbiota-liberated host sugars facilitate post-antibiotic expansion of enteric pathogens. Nature 502, 96–99 (2013).
Ferreyra, J. A. et al. Gut microbiota-produced succinate promotes C. difficile infection after antibiotic treatment or motility disturbance. Cell Host Microbe 16, 770–777 (2014).
Buffie, C. G. et al. Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile. Nature 517, 205–208 (2015).
McDonald, J. A. K. et al. Inhibiting growth of Clostridioides difficile by restoring valerate, produced by the intestinal microbiota. Gastroenterology 155, 1495–1507.e15 (2018).
Cho, J. et al. Clostridioides difficile whole genome sequencing differentiates relapse with the same strain from reinfection with a new strain. Clin. Infect. Dis. 72, 806–813 (2021).
Boyd, C. D. & O’Toole, G. A. Second messenger regulation of biofilm formation: breakthroughs in understanding c-di-GMP effector systems. Annu. Rev. Cell Dev. Biol. 28, 439–462 (2012).
Liubakka, A. & Vaughn, B. P. Clostridium difficile infection and fecal microbiota transplant. AACN Adv. Crit. Care 27, 324–337 (2016).
Tariq, R., Saha, S., Solanky, D., Pardi, D. S. & Khanna, S. Predictors and management of failed fecal microbiota transplantation for recurrent Clostridioides difficile infection. J. Clin. Gastroenterol. 55, 542–547 (2021).
Kelly, C, R. et al. Fecal microbiota transplant is highly effective in real-world practice: initial results from the FMT National Registry. Gastroenterology 160, 183–192.e3 (2021).
DeFilipp, Z. et al. Drug-resistant E. coli bacteremia transmitted by fecal microbiota transplant. N. Engl. J. Med. 381, 2043–2050 (2019).
Khanna, S. et al. Gut microbiome predictors of treatment response and recurrence in primary Clostridium difficile infection. Aliment. Pharmacol. Ther. 44, 715–727 (2016).
Seekatz, A. M. & Young, V. B. Clostridium difficile and the microbiota. J. Clin. Invest. 124, 4182–4189 (2014).
Blount, K. F., Shannon, W. D., Deych, E. & Jones, C. Restoration of bacterial microbiome composition and diversity among treatment responders in a phase 2 trial of RBX2660: an investigational microbiome restoration therapeutic. Open. Forum Infect. Dis. 6, ofz095 (2019).
US National Library of Medicine. ClinicalTrials.gov https://ClinicalTrials.gov/show/NCT03110133.
US National Library of Medicine. ClinicalTrials.gov https://ClinicalTrials.gov/show/NCT03244644.
Gosálbez, L. The microbiome biotech landscape: an analysis of the pharmaceutical pipeline. Microbiome Times https://www.microbiometimes.com/the-microbiome-biotech-landscape-an-analysis-of-the-pharmaceutical-pipeline/ (2020).
Zitvogel, L., Ayyoub, M., Routy, B. & Kroemer, G. Microbiome and anticancer immunosurveillance. Cell 165, 276–287 (2016).
Zitvogel, L., Daillere, R., Roberti, M. P., Routy, B. & Kroemer, G. Anticancer effects of the microbiome and its products. Nat. Rev. Microbiol. 15, 465–478 (2017).
Kadosh, E. et al. The gut microbiome switches mutant p53 from tumour-suppressive to oncogenic. Nature 586, 133–138 (2020).
Raskov, H., Burcharth, J. & Pommergaard, H. C. Linking gut microbiota to colorectal cancer. J. Cancer 8, 3378–3395 (2017).
Pleguezuelos-Manzano, C. et al. Mutational signature in colorectal cancer caused by genotoxic pks+ E. coli. Nature 580, 269–273 (2020).
Riquelme, E. et al. Tumor microbiome diversity and composition influence pancreatic cancer outcomes. Cell 178, 795–806.e12 (2019).
Alexander, J. L. et al. Gut microbiota modulation of chemotherapy efficacy and toxicity. Nat. Rev. Gastroenterol. Hepatol. 14, 356–365 (2017).
Schiavoni, G. et al. Cyclophosphamide synergizes with type I interferons through systemic dendritic cell reactivation and induction of immunogenic tumor apoptosis. Cancer Res. 71, 768–778 (2011).
Viaud, S. et al. Cyclophosphamide induces differentiation of Th17 cells in cancer patients. Cancer Res. 71, 661–665 (2011).
Viaud, S. et al. The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide. Science 342, 971–976 (2013).
Iida, N. et al. Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment. Science 342, 967–970 (2013).
Panebianco, C., Andriulli, A. & Pazienza, V. Pharmacomicrobiomics: exploiting the drug-microbiota interactions in anticancer therapies. Microbiome 6, 92 (2018).
Routy, B. et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science 359, 91–97 (2018).
Derosa, L. et al. Negative association of antibiotics on clinical activity of immune checkpoint inhibitors in patients with advanced renal cell and non-small-cell lung cancer. Ann. Oncol. 29, 1437–1444 (2018).
Vetizou, M. et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science 350, 1079–1084 (2015).
Mager, L. F. et al. Microbiome-derived inosine modulates response to checkpoint inhibitor immunotherapy. Science 369, 1481–1489 (2020).
Sivan, A. et al. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science 350, 1084–1089 (2015).
Matson, V. et al. The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients. Science 359, 104–108 (2018).
Gopalakrishnan, V. et al. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science 359, 97–103 (2018).
Fu, Z. D., Selwyn, F. P., Cui, J. Y. & Klaassen, C. D. RNA-Seq profiling of intestinal expression of xenobiotic processing genes in germ-free mice. Drug. Metab. Dispos. 45, 1225–1238 (2017).
Nichols, R. G., Peters, J. M. & Patterson, A. D. Interplay between the host, the human microbiome, and drug metabolism. Hum. Genomics 13, 27 (2019).
Diasio, R. B. Sorivudine and 5-fluorouracil; a clinically significant drug-drug interaction due to inhibition of dihydropyrimidine dehydrogenase. Br. J. Clin. Pharmacol. 46, 1–4 (1998).
Nakayama, H. et al. Intestinal anaerobic bacteria hydrolyse sorivudine, producing the high blood concentration of 5-(E)-(2-bromovinyl)uracil that increases the level and toxicity of 5-fluorouracil. Pharmacogenetics 7, 35–43 (1997).
Wallace, B. D. et al. Alleviating cancer drug toxicity by inhibiting a bacterial enzyme. Science 330, 831–835 (2010).
Kodawara, T. et al. The inhibitory effect of ciprofloxacin on the beta-glucuronidase-mediated deconjugation of the irinotecan metabolite SN-38-G. Basic Clin. Pharmacol. Toxicol. 118, 333–337 (2016).
Mego, M. et al. Prevention of irinotecan induced diarrhea by probiotics: a randomized double blind, placebo controlled pilot study. Complement. Ther. Med. 23, 356–362 (2015).
Bhatt, A. P. et al. Targeted inhibition of gut bacterial beta-glucuronidase activity enhances anticancer drug efficacy. Proc. Natl Acad. Sci. USA 117, 7374–7381 (2020).
Yamamoto, K. et al. Relationship between adverse events and microbiomes in advanced hepatocellular carcinoma patients treated with sorafenib. Anticancer. Res. 40, 665–676 (2020).
Ianiro, G. et al. Faecal microbiota transplantation for the treatment of diarrhoea induced by tyrosine-kinase inhibitors in patients with metastatic renal cell carcinoma. Nat. Commun. 11, 4333 (2020).
Whidbey, C. et al. A probe-enabled approach for the selective isolation and characterization of functionally active subpopulations in the gut microbiome. J. Am. Chem. Soc. 141, 42–47 (2019).
Hales, C. M., Carroll, M. D., Fryar, C. D. & Ogden, C. L. Prevalence of obesity and severe obesity among adults: United States, 2017-2018. NCHS Data Brief 360, 1–8 (2020).
Sze, M. A. & Schloss, P. D. Looking for a signal in the noise: revisiting obesity and the microbiome. mBio 7, e01018-16 (2016).
Ley, R. E. et al. Obesity alters gut microbial ecology. Proc. Natl Acad. Sci. USA 102, 11070–11075 (2005).
Ley, R. E. Obesity and the human microbiome. Curr. Opin. Gastroenterol. 26, 5–11 (2010).
Turnbaugh, P. J. et al. A core gut microbiome in obese and lean twins. Nature 457, 480–484 (2009).
Waldram, A. et al. Top-down systems biology modeling of host metabotype-microbiome associations in obese rodents. J. Proteome Res. 8, 2361–2375 (2009).
Turnbaugh, P. J., Backhed, F., Fulton, L. & Gordon, J. I. Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome. Cell Host Microbe 3, 213–223 (2008).
Ridaura, V. K. et al. Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science 341, 1241214 (2013).
Turnbaugh, P. J. et al. The effect of diet on the human gut microbiome: a metagenomic analysis in humanized gnotobiotic mice. Sci. Transl Med. 1, 6ra14 (2009).
Backhed, F. et al. The gut microbiota as an environmental factor that regulates fat storage. Proc. Natl Acad. Sci. USA 101, 15718–15723 (2004).
Turnbaugh, P. J. et al. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444, 1027–1031 (2006).
Scheithauer, T. P., Dallinga-Thie, G. M., de Vos, W. M., Nieuwdorp, M. & van Raalte, D. H. Causality of small and large intestinal microbiota in weight regulation and insulin resistance. Mol. Metab. 5, 759–770 (2016).
Cani, P. D. et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 56, 1761–1772 (2007).
Belizario, J. E., Faintuch, J. & Garay-Malpartida, M. Gut microbiome dysbiosis and immunometabolism: new frontiers for treatment of metabolic diseases. Mediators Inflamm. 2018, 2037838 (2018).
Clarke, G. et al. Minireview: gut microbiota: the neglected endocrine organ. Mol. Endocrinol. 28, 1221–1238 (2014).
Davis, C. D. The gut microbiome and its role in obesity. Nutr. Today 51, 167–174 (2016).
Ejtahed, H. S., Angoorani, P., Soroush, A. R. & Atlasi, R. Probiotics supplementation for the obesity management; a systematic review of animal studies and clinical trials. Funct. Foods 52, 228–242 (2019).
Cerdo, T., Garcia-Santos, J. A., M, G. B. & Campoy, C. The role of probiotics and prebiotics in the prevention and treatment of obesity. Nutrients 11, 635 (2019).
David, L. A. et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature 505, 559–563 (2014).
Smits, S. A., Marcobal, A., Higginbottom, S., Sonnenburg, J. L. & Kashyap, P. C. Individualized responses of gut microbiota to dietary intervention modeled in humanized mice. mSystems 1, e00098-16 (2016).
Kovatcheva-Datchary, P. et al. Simplified intestinal microbiota to study microbe-diet-host interactions in a mouse model. Cell Rep. 26, 3772–3783.e6 (2019).
Muniz Pedrogo, D. A. et al. Gut microbial carbohydrate metabolism hinders weight loss in overweight adults undergoing lifestyle intervention with a volumetric diet. Mayo Clin. Proc. 93, 1104–1110 (2018).
Korem, T. et al. Bread affects clinical parameters and induces gut microbiome-associated personal glycemic responses. Cell Metab. 25, 1243–1253.e5 (2017).
Zeevi, D. et al. Personalized nutrition by prediction of glycemic responses. Cell 163, 1079–1094 (2015).
Berry, S. E. et al. Human postprandial responses to food and potential for precision nutrition. Nat. Med. 26, 964–973 (2020).
Jumpertz, R. et al. Energy-balance studies reveal associations between gut microbes, caloric load, and nutrient absorption in humans. Am. J. Clin. Nutr. 94, 58–65 (2011).
Kolodziejczyk, A. A., Zheng, D. & Elinav, E. Diet-microbiota interactions and personalized nutrition. Nat. Rev. Microbiol. 17, 742–753 (2019).
Korpela, K. et al. Gut microbiota signatures predict host and microbiota responses to dietary interventions in obese individuals. PLoS ONE 9, e90702 (2014).
Zmora, N., Suez, J. & Elinav, E. You are what you eat: diet, health and the gut microbiota. Nat. Rev. Gastroenterol. Hepatol. 16, 35–56 (2019).
Zhao, L. et al. A glucagon-like peptide-1 receptor agonist lowers weight by modulating the structure of gut microbiota. Front. Endocrinol. 9, 233 (2018).
Ejtahed, H. S. et al. Adaptation of human gut microbiota to bariatric surgeries in morbidly obese patients: a systematic review. Microb. Pathog. 116, 13–21 (2018).
Liu, R. et al. Gut microbiome and serum metabolome alterations in obesity and after weight-loss intervention. Nat. Med. 23, 859–868 (2017).
Plovier, H. et al. A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice. Nat. Med. 23, 107–113 (2017).
Depommier, C. et al. Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study. Nat. Med. 25, 1096–1103 (2019).
Goodrich, J. K. et al. Human genetics shape the gut microbiome. Cell 159, 789–799 (2014).
US National Library of Medicine. ClinicalTrials.gov https://ClinicalTrials.gov/show/NCT04663139.
Choi, B. S., Daoust, L., Pilon, G., Marette, A. & Tremblay, A. Potential therapeutic applications of the gut microbiome in obesity: from brain function to body detoxification. Int. J. Obes. 44, 1818–1831 (2020).
Forslund, K. et al. Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota. Nature 528, 262–266 (2015).
Mandic, A. D. et al. Clostridium ramosum regulates enterochromaffin cell development and serotonin release. Sci. Rep. 9, 1177 (2019).
Karlsson, F. H. et al. Gut metagenome in European women with normal, impaired and diabetic glucose control. Nature 498, 99–103 (2013).
de Groot, P. et al. Donor metabolic characteristics drive effects of faecal microbiota transplantation on recipient insulin sensitivity, energy expenditure and intestinal transit time. Gut 69, 502–512 (2020).
Vrieze, A. et al. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology 143, 913–916.e7 (2012).
Zhao, L. et al. Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes. Science 359, 1151–1156 (2018).
Pedersen, H. K. et al. Human gut microbes impact host serum metabolome and insulin sensitivity. Nature 535, 376–381 (2016).
Koh, A. et al. Microbially produced imidazole propionate impairs insulin signaling through mTORC1. Cell 175, 947–961.e17 (2018).
Home, P., Mant, J., Diaz, J. & Turner, C., Guideline Development Group. Management of type 2 diabetes: summary of updated NICE guidance. BMJ 336, 1306–1308 (2008).
Mendes-Soares, H. et al. Assessment of a personalized approach to predicting postprandial glycemic responses to food among individuals without diabetes. JAMA Netw. Open. 2, e188102 (2019).
Rena, G., Hardie, D. G. & Pearson, E. R. The mechanisms of action of metformin. Diabetologia 60, 1577–1585 (2017).
Shin, N. R. et al. An increase in the Akkermansia spp. population induced by metformin treatment improves glucose homeostasis in diet-induced obese mice. Gut 63, 727–735 (2014).
Zhang, X. et al. Modulation of gut microbiota by berberine and metformin during the treatment of high-fat diet-induced obesity in rats. Sci. Rep. 5, 14405 (2015).
Lee, H. & Ko, G. Effect of metformin on metabolic improvement and gut microbiota. Appl. Env. Microbiol. 80, 5935–5943 (2014).
Matheus, V. A., Monteiro, L., Oliveira, R. B., Maschio, D. A. & Collares-Buzato, C. B. Butyrate reduces high-fat diet-induced metabolic alterations, hepatic steatosis and pancreatic beta cell and intestinal barrier dysfunctions in prediabetic mice. Exp. Biol. Med. 242, 1214–1226 (2017).
Croset, M. et al. Rat small intestine is an insulin-sensitive gluconeogenic organ. Diabetes 50, 740–746 (2001).
De Vadder, F. et al. Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits. Cell 156, 84–96 (2014).
Bryrup, T. et al. Metformin-induced changes of the gut microbiota in healthy young men: results of a non-blinded, one-armed intervention study. Diabetologia 62, 1024–1035 (2019).
Madsen, M. S. A. et al. Metabolic and gut microbiome changes following GLP-1 or dual GLP-1/GLP-2 receptor agonist treatment in diet-induced obese mice. Sci. Rep. 9, 15582 (2019).
Perraudeau, F. et al. Improvements to postprandial glucose control in subjects with type 2 diabetes: a multicenter, double blind, randomized placebo-controlled trial of a novel probiotic formulation. BMJ Open Diabetes Res. Care 8, e001319 (2020).
Tripathi, A. et al. The gut-liver axis and the intersection with the microbiome. Nat. Rev. Gastroenterol. Hepatol. 15, 397–411 (2018).
Mouzaki, M. et al. Intestinal microbiota in patients with nonalcoholic fatty liver disease. Hepatology 58, 120–127 (2013).
Mohammadi, Z. et al. Fecal microbiota in non-alcoholic fatty liver disease and non-alcoholic steatohepatitis: a systematic review. Arch. Iran. Med. 23, 44–52 (2020).
Leung, C., Rivera, L., Furness, J. B. & Angus, P. W. The role of the gut microbiota in NAFLD. Nat. Rev. Gastroenterol. Hepatol. 13, 412–425 (2016).
Le Roy, T. et al. Intestinal microbiota determines development of non-alcoholic fatty liver disease in mice. Gut 62, 1787–1794 (2013).
Zhu, L. et al. Characterization of gut microbiomes in nonalcoholic steatohepatitis (NASH) patients: a connection between endogenous alcohol and NASH. Hepatology 57, 601–609 (2013).
Dawes, E. A. & Foster, S. M. The formation of ethanol in Escherichia coli. Biochim. Biophys. Acta 22, 253–265 (1956).
Malik, F., Wickremesinghe, P. & Saverimuttu, J. Case report and literature review of auto-brewery syndrome: probably an underdiagnosed medical condition. BMJ Open. Gastroenterol. 6, e000325 (2019).
Brandt, A. et al. Metformin attenuates the onset of non-alcoholic fatty liver disease and affects intestinal microbiota and barrier in small intestine. Sci. Rep. 9, 6668 (2019).
Li, Y., Liu, L., Wang, B., Wang, J. & Chen, D. Metformin in non-alcoholic fatty liver disease: a systematic review and meta-analysis. Biomed. Rep. 1, 57–64 (2013).
Ma, J., Zhou, Q. & Li, H. Gut microbiota and nonalcoholic fatty liver disease: insights on mechanisms and therapy. Nutrients 9, 1124 (2017).
Zhou, D. et al. Total fecal microbiota transplantation alleviates high-fat diet-induced steatohepatitis in mice via beneficial regulation of gut microbiota. Sci. Rep. 7, 1529 (2017).
Garcia-Lezana, T. et al. Restoration of a healthy intestinal microbiota normalizes portal hypertension in a rat model of nonalcoholic steatohepatitis. Hepatology 67, 1485–1498 (2018).
Craven, L. et al. Allogenic fecal microbiota transplantation in patients with nonalcoholic fatty liver disease improves abnormal small intestinal permeability: a randomized control trial. Am. J. Gastroenterol. 115, 1055–1065 (2020).
Witjes, J. J. et al. Donor fecal microbiota transplantation alters gut microbiota and metabolites in obese individuals with steatohepatitis. Hepatol. Commun. 4, 1578–1590 (2020).
US National Library of Medicine. ClinicalTrials.govhttps://ClinicalTrials.gov/show/NCT02469272.
US National Library of Medicine. ClinicalTrials.gov https://ClinicalTrials.gov/show/NCT03803540.
Alisi, A. et al. Randomised clinical trial: The beneficial effects of VSL#3 in obese children with non-alcoholic steatohepatitis. Aliment. Pharmacol. Ther. 39, 1276–1285 (2014).
Malaguarnera, M. et al. Bifidobacterium longum with fructo-oligosaccharides in patients with non alcoholic steatohepatitis. Dig. Dis. Sci. 57, 545–553 (2012).
Wong, V. W. et al. Treatment of nonalcoholic steatohepatitis with probiotics. A proof-of-concept study. Ann. Hepatol. 12, 256–262 (2013).
Wong, V. W. et al. Molecular characterization of the fecal microbiota in patients with nonalcoholic steatohepatitis–a longitudinal study. PLoS ONE 8, e62885 (2013).
Duan, Y. et al. Bacteriophage targeting of gut bacterium attenuates alcoholic liver disease. Nature 575, 505–511 (2019).
GBD 2015 Mortality and Causes of Death Collaborators. Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet 388, 1459–1544 (2016).
Capewell, S. et al. Cardiovascular risk factor trends and potential for reducing coronary heart disease mortality in the United States of America. Bull. World Health Organ. 88, 120–130 (2010).
Novakovic, M. et al. Role of gut microbiota in cardiovascular diseases. World J. Cardiol. 12, 110–122 (2020).
Peng, J., Xiao, X., Hu, M. & Zhang, X. Interaction between gut microbiome and cardiovascular disease. Life Sci. 214, 153–157 (2018).
Organ, C. L. et al. Choline diet and its gut microbe-derived metabolite, trimethylamine n-oxide, exacerbate pressure overload-induced heart failure. Circ. Heart Fail. 9, e002314 (2016).
Tang, W. H. et al. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N. Engl. J. Med. 368, 1575–1584 (2013).
Martinez-Del Campo, A., Romano, K. A., Rey, F. E. & Balskus, E. P. The plot thickens: diet microbe interactions may modulate thrombosis risk. Cell Metab. 23, 573–575 (2016).
Roberts, A. B. et al. Development of a gut microbe-targeted nonlethal therapeutic to inhibit thrombosis potential. Nat. Med. 24, 1407–1417 (2018).
Koeth, R. A. et al. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat. Med. 19, 576–585 (2013).
Zhu, Y., Li, Q. & Jiang, H. Gut microbiota in atherosclerosis: focus on trimethylamine N-oxide. APMIS 128, 353–366 (2020).
Romano, K. A., Vivas, E. I., Amador-Noguez, D. & Rey, F. E. Intestinal microbiota composition modulates choline bioavailability from diet and accumulation of the proatherogenic metabolite trimethylamine-N-oxide. mBio 6, e02481 (2015).
Wang, Z. et al. Non-lethal inhibition of gut microbial trimethylamine production for the treatment of atherosclerosis. Cell 163, 1585–1595 (2015).
Rath, S., Heidrich, B., Pieper, D. H. & Vital, M. Uncovering the trimethylamine-producing bacteria of the human gut microbiota. Microbiome 5, 54 (2017).
Jie, Z. et al. The gut microbiome in atherosclerotic cardiovascular disease. Nat. Commun. 8, 845 (2017).
Ahmad, A. F., Ward, N. C. & Dwivedi, G. The gut microbiome and heart failure. Curr. Opin. Cardiol. 34, 225–232 (2019).
Kamo, T. et al. Dysbiosis and compositional alterations with aging in the gut microbiota of patients with heart failure. PLoS ONE 12, e0174099 (2017).
Liyanage, T. et al. Effects of the Mediterranean diet on cardiovascular outcomes-a systematic review and meta-analysis. PLoS ONE 11, e0159252 (2016).
Wang, D. D. et al. The gut microbiome modulates the protective association between a Mediterranean diet and cardiometabolic disease risk. Nat. Med. 27, 333–343 (2021).
Marques, F. Z. et al. High-fiber diet and acetate supplementation change the gut microbiota and prevent the development of hypertension and heart failure in hypertensive mice. Circulation 135, 964–977 (2017).
Cena, H. & Calder, P. C. Defining a healthy diet: evidence for the role of contemporary dietary patterns in health and disease. Nutrients 12, 334 (2020).
Haiser, H. J., Seim, K. L., Balskus, E. P. & Turnbaugh, P. J. Mechanistic insight into digoxin inactivation by Eggerthella lenta augments our understanding of its pharmacokinetics. Gut Microbes 5, 233–238 (2014).
Spanogiannopoulos, P., Bess, E. N., Carmody, R. N. & Turnbaugh, P. J. The microbial pharmacists within us: a metagenomic view of xenobiotic metabolism. Nat. Rev. Microbiol. 14, 273–287 (2016).
Pencina, M. J. et al. Application of new cholesterol guidelines to a population-based sample. N. Engl. J. Med. 370, 1422–1431 (2014).
Iwaki, Y., Lee, W. & Sugiyama, Y. Comparative and quantitative assessment on statin efficacy and safety: insights into inter-statin and inter-individual variability via dose- and exposure-response relationships. Expert. Opin. Drug Metab. Toxicol. 15, 897–911 (2019).
Sun, B., Li, L. & Zhou, X. Comparative analysis of the gut microbiota in distinct statin response patients in East China. J. Microbiol. 56, 886–892 (2018).
Kaddurah-Daouk, R. et al. Enteric microbiome metabolites correlate with response to simvastatin treatment. PLoS ONE 6, e25482 (2011).
He, X. et al. Gut microbiota modulation attenuated the hypolipidemic effect of simvastatin in high-fat/cholesterol-diet fed mice. J. Proteome Res. 16, 1900–1910 (2017).
Wang, L. et al. The influence of the intestinal microflora to the efficacy of Rosuvastatin. Lipids Health Dis. 17, 151 (2018).
Yoo, D. H. et al. Gut microbiota-mediated drug interactions between lovastatin and antibiotics. Drug. Metab. Dispos. 42, 1508–1513 (2014).
Liu, Y. et al. Gut microbiome associates with lipid-lowering effect of rosuvastatin in vivo. Front. Microbiol. 9, 530 (2018).
Vieira-Silva, S. et al. Statin therapy is associated with lower prevalence of gut microbiota dysbiosis. Nature 581, 310–315 (2020).
Mayerhofer, C. C. K. et al. Design of the GutHeart-targeting gut microbiota to treat heart failure-trial: a phase II, randomized clinical trial. ESC Heart Fail. 5, 977–984 (2018).
US National Library of Medicine. ClinicalTrials.gov https://ClinicalTrials.gov/show/NCT03968549.
Tang, W. H. W., Li, D. Y. & Hazen, S. L. Dietary metabolism, the gut microbiome, and heart failure. Nat. Rev. Cardiol. 16, 137–154 (2019).
Vaahtovuo, J., Munukka, E., Korkeamaki, M., Luukkainen, R. & Toivanen, P. Fecal microbiota in early rheumatoid arthritis. J. Rheumatol. 35, 1500–1505 (2008).
Bodkhe, R., Balakrishnan, B. & Taneja, V. The role of microbiome in rheumatoid arthritis treatment. Ther Adv Musculoskelet Dis 11, 1759720X19844632 (2019).
Marietta, E. V. et al. Suppression of inflammatory arthritis by human gut-derived prevotella histicola in humanized mice. Arthritis Rheumatol. 68, 2878–2888 (2016).
Maeda, Y. et al. Dysbiosis contributes to arthritis development via activation of autoreactive T cells in the intestine. Arthritis Rheumatol. 68, 2646–2661 (2016).
Maeda, Y. & Takeda, K. Host-microbiota interactions in rheumatoid arthritis. Exp. Mol. Med. 51, 1–6 (2019).
Lloyd-Price, J. et al. Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases. Nature 569, 655–662 (2019).
Picchianti-Diamanti, A. et al. Analysis of gut microbiota in rheumatoid arthritis patients: disease-related dysbiosis and modifications induced by etanercept. Int. J. Mol. Sci. 19, 2938 (2018).
Chen, J. et al. An expansion of rare lineage intestinal microbes characterizes rheumatoid arthritis. Genome Med. 8, 43 (2016).
Zhang, X. et al. The oral and gut microbiomes are perturbed in rheumatoid arthritis and partly normalized after treatment. Nat. Med. 21, 895–905 (2015).
Artacho, A. et al. The pre-treatment gut microbiome is associated with lack of response to methotrexate in new onset rheumatoid arthritis. Arthritis Rheumatol. 73, 931–942 (2020).
Nayak, R. R. et al. Methotrexate impacts conserved pathways in diverse human gut bacteria leading to decreased host immune activation. Cell Host Microbe 29, 362–377.e11 (2021).
Sayers, E., MacGregor, A. & Carding, S. R. Drug-microbiota interactions and treatment response: Relevance to rheumatoid arthritis. AIMS Microbiol. 4, 642–654 (2018).
Ince, A., Yazici, Y., Hamuryudan, V. & Yazici, H. The frequency and clinical characteristics of methotrexate (MTX) oral toxicity in rheumatoid arthritis (RA): a masked and controlled study. Clin. Rheumatol. 15, 491–494 (1996).
Zhou, B. et al. Induction and amelioration of methotrexate-induced gastrointestinal toxicity are related to immune response and gut microbiota. EBioMedicine 33, 122–133 (2018).
Schrezenmeier, E. & Dorner, T. Mechanisms of action of hydroxychloroquine and chloroquine: implications for rheumatology. Nat. Rev. Rheumatol. 16, 155–166 (2020).
Scher, J. U. & Abramson, S. B. The microbiome and rheumatoid arthritis. Nat. Rev. Rheumatol. 7, 569–578 (2011).
Zheng, H. et al. Modulation of gut microbiome composition and function in experimental colitis treated with sulfasalazine. Front. Microbiol. 8, 1703 (2017).
LoGuidice, A., Wallace, B. D., Bendel, L., Redinbo, M. R. & Boelsterli, U. A. Pharmacologic targeting of bacterial beta-glucuronidase alleviates nonsteroidal anti-inflammatory drug-induced enteropathy in mice. J. Pharmacol. Exp. Ther. 341, 447–454 (2012).
Saitta, K. S. et al. Bacterial beta-glucuronidase inhibition protects mice against enteropathy induced by indomethacin, ketoprofen or diclofenac: mode of action and pharmacokinetics. Xenobiotica 44, 28–35 (2014).
Clayton, T. A., Baker, D., Lindon, J. C., Everett, J. R. & Nicholson, J. K. Pharmacometabonomic identification of a significant host-microbiome metabolic interaction affecting human drug metabolism. Proc. Natl Acad. Sci. USA 106, 14728–14733 (2009).
So, J. S. et al. Lactobacillus casei suppresses experimental arthritis by down-regulating T helper 1 effector functions. Mol. Immunol. 45, 2690–2699 (2008).
Mandel, D. R., Eichas, K. & Holmes, J. Bacillus coagulans: a viable adjunct therapy for relieving symptoms of rheumatoid arthritis according to a randomized, controlled trial. BMC Complement. Altern. Med. 10, 1 (2010).
Lopez, J. & Grinspan, A. Fecal microbiota transplantation for inflammatory bowel disease. Gastroenterol. Hepatol. 12, 374–379 (2016).
Singh, S. et al. Systematic review with meta-analysis: faecal diversion for management of perianal Crohn’s disease. Aliment. Pharmacol. Ther. 42, 783–792 (2015).
Nitzan, O., Elias, M., Peretz, A. & Saliba, W. Role of antibiotics for treatment of inflammatory bowel disease. World J. Gastroenterol. 22, 1078–1087 (2016).
Chassaing, B. & Darfeuille-Michaud, A. The commensal microbiota and enteropathogens in the pathogenesis of inflammatory bowel diseases. Gastroenterology 140, 1720–1728 (2011).
Britton, G. J. et al. Defined microbiota transplant restores Th17/RORγt+ regulatory T cell balance in mice colonized with inflammatory bowel disease microbiotas. Proc. Natl Acad. Sci. USA 117, 21536–21545 (2020).
Machiels, K. et al. A decrease of the butyrate-producing species Roseburia hominis and Faecalibacterium prausnitzii defines dysbiosis in patients with ulcerative colitis. Gut 63, 1275–1283 (2014).
Sokol, H. et al. Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc. Natl Acad. Sci. USA 105, 16731–16736 (2008).
Kumar, M., Garand, M. & Al Khodor, S. Integrating omics for a better understanding of inflammatory bowel disease: a step towards personalized medicine. J. Transl Med. 17, 419 (2019).
Negroni, A. et al. Characterization of adherent-invasive Escherichia coli isolated from pediatric patients with inflammatory bowel disease. Inflamm. Bowel Dis. 18, 913–924 (2012).
Campos, N. et al. Macrophages from IBD patients exhibit defective tumour necrosis factor-alpha secretion but otherwise normal or augmented pro-inflammatory responses to infection. Immunobiology 216, 961–970 (2011).
Sasaki, M. et al. Invasive Escherichia coli are a feature of Crohn’s disease. Lab. Invest. 87, 1042–1054 (2007).
Zeng, M. Y., Inohara, N. & Nunez, G. Mechanisms of inflammation-driven bacterial dysbiosis in the gut. Mucosal Immunol. 10, 18–26 (2017).
Gevers, D. et al. The treatment-naive microbiome in new-onset Crohn’s disease. Cell Host Microbe 15, 382–392 (2014).
Scales, B. S., Dickson, R. P. & Huffnagle, G. B. A tale of two sites: how inflammation can reshape the microbiomes of the gut and lungs. J. Leukoc. Biol. 100, 943–950 (2016).
Garsin, D. A. Ethanolamine utilization in bacterial pathogens: roles and regulation. Nat. Rev. Microbiol. 8, 290–295 (2010).
Fornelos, N. et al. Growth effects of N-acylethanolamines on gut bacteria reflect altered bacterial abundances in inflammatory bowel disease. Nat. Microbiol. 5, 486–497 (2020).
Ni, J. et al. A role for bacterial urease in gut dysbiosis and Crohn’s disease. Sci. Transl Med. 9, eaah6888 (2017).
Lewis, J. D. et al. Inflammation, antibiotics, and diet as environmental stressors of the gut microbiome in pediatric Crohn’s disease. Cell Host Microbe 22, 247 (2017).
Martin, R. et al. Functional characterization of novel faecalibacterium prausnitzii strains isolated from healthy volunteers: a step forward in the use of F. prausnitzii as a next-generation probiotic. Front. Microbiol. 8, 1226 (2017).
Ananthakrishnan, A. N. et al. Gut microbiome function predicts response to anti-integrin biologic therapy in inflammatory bowel diseases. Cell Host Microbe 21, 603–610.e3 (2017).
Rajca, S. et al. Alterations in the intestinal microbiome (dysbiosis) as a predictor of relapse after infliximab withdrawal in Crohn’s disease. Inflamm. Bowel Dis. 20, 978–986 (2014).
Jeong, D. Y. et al. Induction and maintenance treatment of inflammatory bowel disease: a comprehensive review. Autoimmun. Rev. 18, 439–454 (2019).
McIlroy, J., Ianiro, G., Mukhopadhya, I., Hansen, R. & Hold, G. L. Review article: the gut microbiome in inflammatory bowel disease-avenues for microbial management. Aliment. Pharmacol. Ther. 47, 26–42 (2018).
Zhang, M. et al. Faecalibacterium prausnitzii inhibits interleukin-17 to ameliorate colorectal colitis in rats. PLoS ONE 9, e109146 (2014).
Huang, X. L. et al. Faecalibacterium prausnitzii supernatant ameliorates dextran sulfate sodium induced colitis by regulating Th17 cell differentiation. World J. Gastroenterol. 22, 5201–5210 (2016).
Zhou, L. et al. Faecalibacterium prausnitzii produces butyrate to maintain Th17/Treg balance and to ameliorate colorectal colitis by inhibiting histone deacetylase 1. Inflamm. Bowel Dis. 24, 1926–1940 (2018).
Moayyedi, P. et al. Fecal microbiota transplantation induces remission in patients with active ulcerative colitis in a randomized controlled trial. Gastroenterology 149, 102–109.e6 (2015).
Hill, D. A. & Spergel, J. M. The atopic march: critical evidence and clinical relevance. Ann. Allergy Asthma Immunol. 120, 131–137 (2018).
Iweala, O. I. & Nagler, C. R. The microbiome and food allergy. Annu. Rev. Immunol. 37, 377–403 (2019).
Huang, Y. J. et al. The microbiome in allergic disease: current understanding and future opportunities-2017 PRACTALL document of the American Academy of Allergy, Asthma & Immunology and the European Academy of Allergy and Clinical Immunology. J. Allergy Clin. Immunol. 139, 1099–1110 (2017).
Berin, M. C. & Sampson, H. A. Mucosal immunology of food allergy. Curr. Biol. 23, R389–R400 (2013).
Zhao, W., Ho, H. E. & Bunyavanich, S. The gut microbiome in food allergy. Ann. Allergy Asthma Immunol. 122, 276–282 (2019).
Bunyavanich, S. et al. Early-life gut microbiome composition and milk allergy resolution. J. Allergy Clin. Immunol. 138, 1122–1130 (2016).
Fazlollahi, M. et al. Early-life gut microbiome and egg allergy. Allergy 73, 1515–1524 (2018).
Thompson-Chagoyan, O. C., Vieites, J. M., Maldonado, J., Edwards, C. & Gil, A. Changes in faecal microbiota of infants with cow’s milk protein allergy–a Spanish prospective case-control 6-month follow-up study. Pediatr. Allergy Immunol. 21, e394–e400 (2010).
Feehley, T. et al. Healthy infants harbor intestinal bacteria that protect against food allergy. Nat. Med. 25, 448–453 (2019).
Abdel-Gadir, A. et al. Microbiota therapy acts via a regulatory T cell MyD88/RORγt pathway to suppress food allergy. Nat. Med. 25, 1164–1174 (2019).
Furusawa, Y. et al. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature 504, 446–450 (2013).
Berni Canani, R. et al. Specific signatures of the gut microbiota and increased levels of butyrate in children treated with fermented cow’s milk containing heat-killed Lactobacillus paracasei CBA L74. Appl Environ Microbiol 83, e01206-17 (2017).
Berni Canani, R. et al. Effect of Lactobacillus GG on tolerance acquisition in infants with cow’s milk allergy: a randomized trial. J. Allergy Clin. Immunol. 129, 580–582 (2012).
Lynch, S. V. & Boushey, H. A. The microbiome and development of allergic disease. Curr. Opin. Allergy Clin. Immunol. 16, 165–171 (2016).
Fujimura, K. E. et al. Neonatal gut microbiota associates with childhood multisensitized atopy and T cell differentiation. Nat. Med. 22, 1187–1191 (2016).
Stein, M. M. et al. Innate immunity and asthma risk in Amish and Hutterite farm children. N. Engl. J. Med. 375, 411–421 (2016).
Olszak, T. et al. Microbial exposure during early life has persistent effects on natural killer T cell function. Science 336, 489–493 (2012).
Arrieta, M. C. et al. Early infancy microbial and metabolic alterations affect risk of childhood asthma. Sci. Transl Med. 7, 307ra152 (2015).
Barcik, W. et al. Histamine-secreting microbes are increased in the gut of adult asthma patients. J. Allergy Clin. Immunol. 138, 1491–1494.e7 (2016).
Ege, M. J. et al. Exposure to environmental microorganisms and childhood asthma. N. Engl. J. Med. 364, 701–709 (2011).
Schuijs, M. J. et al. Farm dust and endotoxin protect against allergy through A20 induction in lung epithelial cells. Science 349, 1106–1110 (2015).
Hammad, H. et al. House dust mite allergen induces asthma via Toll-like receptor 4 triggering of airway structural cells. Nat. Med. 15, 410–416 (2009).
Debarry, J. et al. Acinetobacter lwoffii and Lactococcus lactis strains isolated from farm cowsheds possess strong allergy-protective properties. J. Allergy Clin. Immunol. 119, 1514–1521 (2007).
Frati, F. et al. The role of the microbiome in asthma: the gut–lung axis. Int. J. Mol. Sci. 20, 123 (2018).
Penders, J. et al. Gut microbiota composition and development of atopic manifestations in infancy: the KOALA Birth Cohort Study. Gut 56, 661–667 (2007).
van Nimwegen, F. A. et al. Mode and place of delivery, gastrointestinal microbiota, and their influence on asthma and atopy. J. Allergy Clin. Immunol. 128, 948–955.e1-3 (2011).
Bjorksten, B., Sepp, E., Julge, K., Voor, T. & Mikelsaar, M. Allergy development and the intestinal microflora during the first year of life. J. Allergy Clin. Immunol. 108, 516–520 (2001).
Trompette, A. et al. Gut microbiota metabolism of dietary fiber influences allergic airway disease and hematopoiesis. Nat. Med. 20, 159–166 (2014).
Fujimura, K. E. & Lynch, S. V. Microbiota in allergy and asthma and the emerging relationship with the gut microbiome. Cell Host Microbe 17, 592–602 (2015).
Levan, S. R. et al. Elevated faecal 12,13-diHOME concentration in neonates at high risk for asthma is produced by gut bacteria and impedes immune tolerance. Nat. Microbiol. 4, 1851–1861 (2019).
Durack, J. et al. Delayed gut microbiota development in high-risk for asthma infants is temporarily modifiable by Lactobacillus supplementation. Nat. Commun. 9, 707 (2018).
Vujkovic-Cvijin, I. et al. Host variables confound gut microbiota studies of human disease. Nature 587, 448–454 (2020).
Mars, R. A. T. et al. Longitudinal multi-omics reveals subset-specific mechanisms underlying irritable bowel syndrome. Cell 182, 1460–1473.e17 (2020).
Poyet, M. et al. A library of human gut bacterial isolates paired with longitudinal multiomics data enables mechanistic microbiome research. Nat. Med. 25, 1442–1452 (2019).
Javdan, B. et al. Personalized mapping of drug metabolism by the human gut microbiome. Cell 181, 1661–1679.e22 (2020).
Blaser, M. J. Missing microbes: how the overuse of antibiotics is fueling our modern plagues. Emerg. Infect. Dis. 20, 1961 (2014).
Vuotto, C., Moura, I., Barbanti, F., Donelli, G. & Spigaglia, P. Subinhibitory concentrations of metronidazole increase biofilm formation in Clostridium difficile strains. Pathog. Dis. 74, ftv114 (2016).
Maldarelli, G. A. et al. Type IV pili promote early biofilm formation by Clostridium difficile. Pathog. Dis. 74, ftw061 (2016).
Ethapa, T. et al. Multiple factors modulate biofilm formation by the anaerobic pathogen Clostridium difficile. J. Bacteriol. 195, 545–555 (2013).
The authors thank L. Busby for her secretarial assistance. This work is supported by funding from NIH DK114007, Center for Individualized Medicine and Department of Medicine Mayo Clinic, Rochester, MN, USA.
P.C.K. serves on the advisory board of Novome Biotechnologies and is an ad hoc consultant for Otsuka Pharmaceuticals, Pendulum Therapeutics and IP group. The other authors declare no competing interests.
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Schupack, D.A., Mars, R.A.T., Voelker, D.H. et al. The promise of the gut microbiome as part of individualized treatment strategies. Nat Rev Gastroenterol Hepatol 19, 7–25 (2022). https://doi.org/10.1038/s41575-021-00499-1
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