Fecal Transplants: What Is Being Transferred?

Diana P Bojanova, Seth R Bordenstein, Diana P Bojanova, Seth R Bordenstein

Abstract

Fecal transplants are increasingly utilized for treatment of recurrent infections (i.e., Clostridium difficile) in the human gut and as a general research tool for gain-of-function experiments (i.e., gavage of fecal pellets) in animal models. Changes observed in the recipient's biology are routinely attributed to bacterial cells in the donor feces (~1011 per gram of human wet stool). Here, we examine the literature and summarize findings on the composition of fecal matter in order to raise cautiously the profile of its multipart nature. In addition to viable bacteria, which may make up a small fraction of total fecal matter, other components in unprocessed human feces include colonocytes (~107 per gram of wet stool), archaea (~108 per gram of wet stool), viruses (~108 per gram of wet stool), fungi (~106 per gram of wet stool), protists, and metabolites. Thus, while speculative at this point and contingent on the transplant procedure and study system, nonbacterial matter could contribute to changes in the recipient's biology. There is a cautious need for continued reductionism to separate out the effects and interactions of each component.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1. The growth of fecal transplants…
Fig 1. The growth of fecal transplants as reflected in references in PubMed and the estimated composition of human feces.
The charts show (A) the rapid rise in publications on fecal transplants in the National Library of Medicine's search service (PubMed), particularly between 2012 and 2015, and (B) the estimated upper concentration of the biological entity per gram of unprocessed human feces, as cited in the text. Estimates do not necessarily reflect the viable number of the biological entity, and the concentration of the archaea is estimated from a methanogen breath test that is not solely based on the presence of archaea. Concentrations of metabolites, protists, and other entities were not identified.

References

    1. Kassam Z, Hundal R, Marshall JK, Lee CH (2012) Fecal transplant via retention enema for refractory or recurrent Clostridium difficile infection. Archives of Internal Medicine 172: 191–193. 10.1001/archinte.172.2.191
    1. van Nood E, Vrieze A, Nieuwdorp M, Fuentes S, Zoetendal EG, et al. (2013) Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med 368: 407–415. 10.1056/NEJMoa1205037
    1. Yoon SS, Brandt LJ (2010) Treatment of refractory/recurrent C. difficile-associated disease by donated stool transplanted via colonoscopy: a case series of 12 patients. J Clin Gastroenterol 44: 562–566. 10.1097/MCG.0b013e3181dac035
    1. Aas J, Gessert CE, Bakken JS (2003) Recurrent Clostridium difficile colitis: case series involving 18 patients treated with donor stool administered via a nasogastric tube. Clin Infect Dis 36: 580–585.
    1. Rao K, Young VB (2015) Fecal microbiota transplantation for the management of Clostridium difficile infection. Infect Dis Clin North Am 29: 109–122. 10.1016/j.idc.2014.11.009
    1. Borody TJ, Khoruts A (2012) Fecal microbiota transplantation and emerging applications. Nat Rev Gastroenterol Hepatol 9: 88–96.
    1. Vrieze A, Van Nood E, Holleman F, Salojarvi J, Kootte RS, et al. (2012) Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology 143: 913–916. e917 10.1053/j.gastro.2012.06.031
    1. Borody TJ, Leis S, Campbell J, al. e (2011) Fecal microbiota transplantation (FMT) in multiple sclerosis (MS) [abstract]. Am J Gastroenterol 106:S352.
    1. Suskind DL, Brittnacher MJ, Wahbeh G, Shaffer ML, Hayden HS, et al. (2015) Fecal microbial transplant effect on clinical outcomes and fecal microbiome in active Crohn's disease. Inflamm Bowel Dis 21: 556–563. 10.1097/MIB.0000000000000307
    1. Lawley TD, Clare S, Walker AW, Stares MD, Connor TR, et al. (2012) Targeted restoration of the intestinal microbiota with a simple, defined bacteriotherapy resolves relapsing Clostridium difficile disease in mice. PLoS Pathog 8: e1002995 10.1371/journal.ppat.1002995
    1. Petrof EO, Gloor GB, Vanner SJ, Weese SJ, Carter D, et al. (2013) Stool substitute transplant therapy for the eradication of Clostridium difficile infection: 'RePOOPulating' the gut. Microbiome 1:3 10.1186/2049-2618-1-3
    1. Li M, Liang P, Li Z, Wang Y, Zhang G, et al. (2015) Fecal microbiota transplantation and bacterial consortium transplantation have comparable effects on the re-establishment of mucosal barrier function in mice with intestinal dysbiosis. Front Microbiol 6:692 10.3389/fmicb.2015.00692
    1. Hamilton MJ, Weingarden AR, Unno T, Khoruts A, Sadowsky MJ (2013) High-throughput DNA sequence analysis reveals stable engraftment of gut microbiota following transplantation of previously frozen fecal bacteria. Gut Microbes 4: 125–135. 10.4161/gmic.23571
    1. Hamilton MJ, Weingarden AR, Sadowsky MJ, Khoruts A (2012) Standardized frozen preparation for transplantation of fecal microbiota for recurrent Clostridium difficile infection. Am J Gastroenterol 107: 761–767. 10.1038/ajg.2011.482
    1. Khanna S, Pardi DS, Kelly CR, Kraft CS, Dhere T, et al. (2016) A Novel Microbiome Therapeutic Increases Gut Microbial Diversity and Prevents Recurrent Clostridium difficile Infection. The Journal of Infectious Diseases 10.1093/infdis/jiv766
    1. Hevia A, Delgado S, Margolles A, Sánchez B (2015) Application of density gradient for the isolation of the fecal microbial stool component and the potential use thereof. Scientific Reports 5: 16807 10.1038/srep16807
    1. Rose C, Parker A, Jefferson B, Cartmell E (2015) The Characterization of Feces and Urine: A Review of the Literature to Inform Advanced Treatment Technology. Crit Rev Environ Sci Technol 45: 1827–1879.
    1. Stephen AM, Cummings JH (1980) The microbial contribution to human faecal mass. J Med Microbiol 13: 45–56.
    1. Dridi B, Henry M, El Khéchine A, Raoult D, Drancourt M (2009) High Prevalence of Methanobrevibacter smithii and Methanosphaera stadtmanae Detected in the Human Gut Using an Improved DNA Detection Protocol. PLoS ONE 4: e7063 10.1371/journal.pone.0007063
    1. Lurie-Weinberger MN, Gophna U (2015) Archaea in and on the Human Body: Health Implications and Future Directions. PLOS Pathog 11: e1004833 10.1371/journal.ppat.1004833
    1. Chandel DS, Braileanu GT, Chen JH, Chen HH, Panigrahi P (2011) Live colonocytes in newborn stool: surrogates for evaluation of gut physiology and disease pathogenesis. Pediatr Res 70: 153–158. 10.1038/pr.2011.378
    1. Fonti R, Latella G, Bises G, Magliocca F, Nobili F, et al. (1994) Human colonocytes in primary culture: a model to study epithelial growth, metabolism and differentiation. International Journal of Colorectal Disease 9: 13–22.
    1. Nair PP (2002) Isolated colonocytes. United States Patent US6335193.
    1. Chehoud C, Dryga A, Hwang Y, Nagy-Szakal D, Hollister EB, et al. (2016) Transfer of Viral Communities between Human Individuals during Fecal Microbiota Transplantation. mBio 7: e00322–00316. 10.1128/mBio.00322-16
    1. Bihl F, Castelli D, Marincola F, Dodd RY, Brander C (2007) Transfusion-transmitted infections. Journal of Translational Medicine 5: 25–25.
    1. Gabriel M, Silvio DP, David H, Michael A, Moshe D, et al. (1991) Transfusion Reactions Due to Bacterial Contamination of Blood and Blood Products. Reviews of Infectious Diseases 13: 307–314.
    1. Lee CH, Steiner T, Petrof EO, et al. (2016) Frozen vs fresh fecal microbiota transplantation and clinical resolution of diarrhea in patients with recurrent Clostridium difficile infection: A randomized clinical trial. JAMA 315: 142–149. 10.1001/jama.2015.18098
    1. Youngster I, Sauk J, Pindar C, Wilson RG, Kaplan JL, et al. (2014) Fecal Microbiota Transplant for Relapsing Clostridium difficile Infection Using a Frozen Inoculum From Unrelated Donors: A Randomized, Open-Label, Controlled Pilot Study. Clin Infect Dis 58: 1515–1522. 10.1093/cid/ciu135
    1. Sender R, Fuchs S, Milo R (2016) Are We Really Vastly Outnumbered? Revisiting the Ratio of Bacterial to Host Cells in Humans. Cell 164: 337–340. 10.1016/j.cell.2016.01.013
    1. Ben-Amor K, Heilig H, Smidt H, Vaughan EE, Abee T, et al. (2005) Genetic diversity of viable, injured, and dead fecal bacteria assessed by fluorescence-activated cell sorting and 16S rRNA gene analysis. Appl Environ Microbiol 71: 4679–4689.
    1. Satokari R, Mattila E, Kainulainen V, Arkkila PE (2015) Simple faecal preparation and efficacy of frozen inoculum in faecal microbiota transplantation for recurrent Clostridium difficile infection—an observational cohort study. Aliment Pharmacol Ther 41: 46–53. 10.1111/apt.13009
    1. Rachmilewitz D, Katakura K, Karmeli F, Hayashi T, Reinus C, et al. (2004) Toll-like receptor 9 signaling mediates the anti-inflammatory effects of probiotics in murine experimental colitis. Gastroenterology 126: 520–528.
    1. Rachmilewitz D, Karmeli F, Takabayashi K, Hayashi T, Leider-Trejo L, et al. (2002) Immunostimulatory DNA ameliorates experimental and spontaneous murine colitis. Gastroenterology 122: 1428–1441.
    1. Gough E, Shaikh H, Manges AR (2011) Systematic review of intestinal microbiota transplantation (fecal bacteriotherapy) for recurrent Clostridium difficile infection. Clin Infect Dis 53: 994–1002. 10.1093/cid/cir632
    1. Blekhman R, Goodrich JK, Huang K, Sun Q, Bukowski R, et al. (2015) Host genetic variation impacts microbiome composition across human body sites. Genome Biology 16: 1–12.
    1. Goodrich JK, Waters JL, Poole AC, Sutter JL, Koren O, et al. (2014) Human genetics shape the gut microbiome. Cell 159: 789–799. 10.1016/j.cell.2014.09.053
    1. Kassam Z, Lee CH, Yuan Y, Hunt RH (2013) Fecal Microbiota Transplantation for Clostridium difficile Infection: Systematic Review and Meta-Analysis. Am J Gastroenterol 108: 500–508. 10.1038/ajg.2013.59
    1. Moayyedi P, Surette MG, Kim PT, Libertucci J, Wolfe M, et al. (2015) Fecal Microbiota Transplantation Induces Remission in Patients With Active Ulcerative Colitis in a Randomized Controlled Trial. Gastroenterology 149: 102–109. e106 10.1053/j.gastro.2015.04.001
    1. Reeves AE, Koenigsknecht MJ, Bergin IL, Young VB (2012) Suppression of Clostridium difficile in the gastrointestinal tracts of germfree mice inoculated with a murine isolate from the family Lachnospiraceae. Infect Immun 80: 3786–3794. 10.1128/IAI.00647-12
    1. Gerding DN, Meyer T, Lee C, Cohen SH, Murthy UK, et al. (2015) Administration of spores of nontoxigenic Clostridium difficile strain M3 for prevention of recurrent C. difficile infection: a randomized clinical trial. Jama 313: 1719–1727. 10.1001/jama.2015.3725
    1. Kim MS, Park EJ, Roh SW, Bae JW (2011) Diversity and abundance of single-stranded DNA viruses in human feces. Appl Environ Microbiol 77: 8062–8070. 10.1128/AEM.06331-11
    1. Wigington CH, Sonderegger D, Brussaard CPD, Buchan A, Finke JF, et al. (2016) Re-examination of the relationship between marine virus and microbial cell abundances. Nature Microbiology 1: 15024.
    1. Reyes A, Semenkovich NP, Whiteson K, Rohwer F, Gordon JI (2012) Going viral: next generation sequencing applied to human gut phage populations. Nat Rev Microbiol 10: 607–617.
    1. Reyes A, Haynes M, Hanson N, Angly FE, Heath AC, et al. (2010) Viruses in the faecal microbiota of monozygotic twins and their mothers. Nature 466: 334–338. 10.1038/nature09199
    1. Norman JM, Handley SA, Baldridge MT, Droit L, Liu CY, et al. (2015) Disease-specific alterations in the enteric virome in inflammatory bowel disease. Cell 160: 447–460. 10.1016/j.cell.2015.01.002
    1. Dutilh BE, Cassman N, McNair K, Sanchez SE, Silva GG, et al. (2014) A highly abundant bacteriophage discovered in the unknown sequences of human faecal metagenomes. Nat Commun 5: 4498 10.1038/ncomms5498
    1. Sarker SA, Sultana S, Reuteler G, Moine D, Descombes P, et al. (2016) Oral Phage Therapy of Acute Bacterial Diarrhea With Two Coliphage Preparations: A Randomized Trial in Children From Bangladesh. EBioMedicine 4: 124–137. 10.1016/j.ebiom.2015.12.023
    1. Meader E, Mayer MJ, Steverding D, Carding SR, Narbad A (2013) Evaluation of bacteriophage therapy to control Clostridium difficile and toxin production in an in vitro human colon model system. Anaerobe 22: 25–30. 10.1016/j.anaerobe.2013.05.001
    1. Nale JY, Spencer J, Hargreaves KR, Buckley AM, Trzepinski P, et al. (2015) Bacteriophage Combinations Significantly Reduce Clostridium difficile Growth In Vitro and Proliferation In Vivo. Antimicrob Agents Chemother 60: 968–981. 10.1128/AAC.01774-15
    1. Hargreaves KR, Clokie MRJ (2014) Clostridium difficile phages: still difficult? Frontiers in Microbiology 5(184): 10.3389/fmicb.2014.00184
    1. McCallin S, Alam Sarker S, Barretto C, Sultana S, Berger B, et al. (2013) Safety analysis of a Russian phage cocktail: from metagenomic analysis to oral application in healthy human subjects. Virology 443: 187–196. 10.1016/j.virol.2013.05.022
    1. Spellberg B, Guidos R, Gilbert D, Bradley J, Boucher HW, et al. (2008) The epidemic of antibiotic-resistant infections: a call to action for the medical community from the Infectious Diseases Society of America. Clin Infect Dis 46: 155–164. 10.1086/524891
    1. Hill DA, Hoffmann C, Abt MC, Du Y, Kobuley D, et al. (2010) Metagenomic analyses reveal antibiotic-induced temporal and spatial changes in intestinal microbiota with associated alterations in immune cell homeostasis. Mucosal Immunol 3: 148–158. 10.1038/mi.2009.132
    1. Dethlefsen L, Huse S, Sogin ML, Relman DA (2008) The pervasive effects of an antibiotic on the human gut microbiota, as revealed by deep 16S rRNA sequencing. PLoS Biol 6: e280 10.1371/journal.pbio.0060280
    1. Labrie SJ, Samson JE, Moineau S (2010) Bacteriophage resistance mechanisms. Nat Rev Microbiol 8: 317–327. 10.1038/nrmicro2315
    1. Hyman P, Abedon ST (2010) Bacteriophage host range and bacterial resistance. Adv Appl Microbiol 70: 217–248. 10.1016/S0065-2164(10)70007-1
    1. Gaci N, Borrel G, Tottey W, O’Toole PW, Brugère J (2014) Archaea and the human gut: New beginning of an old story. World J Gastroenterol 20: 16062–16078. 10.3748/wjg.v20.i43.16062
    1. Stewart JA, Chadwick VS, Murray A (2006) Carriage, quantification, and predominance of methanogens and sulfate-reducing bacteria in faecal samples. Lett Appl Microbiol 43: 58–63.
    1. Weaver GA, Krause JA, Miller TL, Wolin MJ (1986) Incidence of methanogenic bacteria in a sigmoidoscopy population: an association of methanogenic bacteria and diverticulosis. Gut 27: 698–704.
    1. Jhangi Sushrut G R, Glanz Bonnie, Cook Sandra, Nejad Parham, Ward Doyle, Li Ning, Gerber Georg, Bry Lynn, Weiner Howard (2014) Increased Archaea Species and Changes with Therapy in Gut Microbiome of Multiple Sclerosis Subjects. Neurology 82(10): S24–001..
    1. Schulze J, Sonnenborn U (2009) Yeasts in the gut: from commensals to infectious agents. Dtsch Arztebl Int 106: 837–842. 10.3238/arztebl.2009.0837
    1. Wang ZK, Yang YS, Stefka AT, Sun G, Peng LH (2014) Review article: fungal microbiota and digestive diseases. Aliment Pharmacol Ther 39: 751–766. 10.1111/apt.12665
    1. Ott SJ, Kuhbacher T, Musfeldt M, Rosenstiel P, Hellmig S, et al. (2008) Fungi and inflammatory bowel diseases: Alterations of composition and diversity. Scand J Gastroenterol 43: 831–841. 10.1080/00365520801935434
    1. Rosenbach A, Dignard D, Pierce JV, Whiteway M, Kumamoto CA (2010) Adaptations of Candida albicans for growth in the mammalian intestinal tract. Eukaryot Cell 9: 1075–1086. 10.1128/EC.00034-10
    1. White SJ, Rosenbach A, Lephart P, Nguyen D, Benjamin A, et al. (2007) Self-Regulation of Candida albicans Population Size during GI Colonization. PLoS Pathog 3: e184
    1. Albac S, Schmitz A, Lopez-Alayon C, d'Enfert C, Sautour M, et al. (2016) Candida albicans is able to use M cells as a portal of entry across the intestinal barrier in vitro. Cell Microbiol 18: 195–210. 10.1111/cmi.12495
    1. Ksiadzyna D, Semianow-Wejchert J, Nawrot U, Wlodarczyk K, Paradowski L (2009) Serum concentration of interleukin 10, anti-mannan Candida antibodies and the fungal colonization of the gastrointestinal tract in patients with ulcerative colitis. Adv Med Sci 54: 170–176. 10.2478/v10039-009-0023-6
    1. Standaert-Vitse A, Sendid B, Joossens M, Francois N, Vandewalle-El Khoury P, et al. (2009) Candida albicans colonization and ASCA in familial Crohn's disease. Am J Gastroenterol 104: 1745–1753. 10.1038/ajg.2009.225
    1. Nair P, Lagerholm S, Dutta S, Shami S, Davis K, et al. (2003) Coprocytobiology: on the nature of cellular elements from stools in the pathophysiology of colonic disease. J Clin Gastroenterol 36: S84–93; discussion S94-86.
    1. Maynard CL (2012) Reciprocal Interactions of the Intestinal Microbiota and Immune System. 489: 231–241. 10.1038/nature11551
    1. Magnusson M, Magnusson KE, Sundqvist T, Denneberg T (1991) Impaired intestinal barrier function measured by differently sized polyethylene glycols in patients with chronic renal failure. Gut 32: 754–759.
    1. Vaziri ND, Zhao YY, Pahl MV (2015) Altered intestinal microbial flora and impaired epithelial barrier structure and function in CKD: the nature, mechanisms, consequences and potential treatment. Nephrol Dial Transplant 31: 737–746. 10.1093/ndt/gfv095
    1. Yui S, Nakamura T, Sato T, Nemoto Y, Mizutani T, et al. (2012) Functional engraftment of colon epithelium expanded in vitro from a single adult Lgr5(+) stem cell. Nat Med 18: 618–623. 10.1038/nm.2695
    1. Jung P, Sato T, Merlos-Suarez A, Barriga FM, Iglesias M, et al. (2011) Isolation and in vitro expansion of human colonic stem cells. Nat Med 17: 1225–1227. 10.1038/nm.2470
    1. Mantis NJ, Rol N, Corthésy B (2011) Secretory IgA's Complex Roles in Immunity and Mucosal Homeostasis in the Gut. Mucosal immunology 4: 603–611. 10.1038/mi.2011.41
    1. Dallas SD, Rolfe RD (1998) Binding of Clostridium difficile toxin A to human milk secretory component. Journal of Medical Microbiology 47: 879–888.
    1. Olson A, Diebel LN, Liberati DM (2013) Effect of host defenses on Clostridium difficile toxin-induced intestinal barrier injury. J Trauma Acute Care Surg 74: 983–989; discussion 989–990. 10.1097/TA.0b013e3182858477
    1. Maslowski KM, Vieira AT, Ng A, Kranich J, Sierro F, et al. (2009) Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature 461: 1282–1286. 10.1038/nature08530
    1. Arpaia N, Campbell C, Fan X, Dikiy S, van der Veeken J, et al. (2013) Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature 504: 451–455. 10.1038/nature12726
    1. Furusawa Y, Obata Y, Fukuda S, Endo TA, Nakato G, et al. (2013) Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature 504: 446–450. 10.1038/nature12721
    1. Sonnenburg ED, Smits SA, Tikhonov M, Higginbottom SK, Wingreen NS, et al. (2016) Diet-induced extinctions in the gut microbiota compound over generations. Nature 529: 212–215. 10.1038/nature16504
    1. Sonnenburg ED, Sonnenburg JL (2014) Starving our microbial self: the deleterious consequences of a diet deficient in microbiota-accessible carbohydrates. Cell Metab 20: 779–786. 10.1016/j.cmet.2014.07.003
    1. Horner KL, LeBoeuf RC, McFarland LV, Elmer GW (2000) Dietary fiber affects the onset of Clostridium difficile disease in hamsters. Nutrition Research 20: 1103–1112.
    1. Nicolucci AC, Reimer RA (2016) Prebiotics as a modulator of gut microbiota in paediatric obesity. Pediatr Obes 10.1111/ijpo.12140
    1. Nicolucci AC, Hume MP, Reimer RA (2015) Effect of Prebiotic Fiber Intake on Adiposity and Inflammation in Overweight and Obese Children: Assessing the Role of the Gut Microbiota. Canadian Journal of Diabetes 39: S43.
    1. Machiels K, Joossens M, Sabino J, De Preter V, Arijs I, et al. (2014) A decrease of the butyrate-producing species Roseburia hominis and Faecalibacterium prausnitzii defines dysbiosis in patients with ulcerative colitis. Gut 63: 1275–1283. 10.1136/gutjnl-2013-304833
    1. Sokol H, Seksik P, Furet JP, Firmesse O, Nion-Larmurier I, et al. (2009) Low counts of Faecalibacterium prausnitzii in colitis microbiota. Inflamm Bowel Dis 15: 1183–1189. 10.1002/ibd.20903
    1. Weir TL, Manter DK, Sheflin AM, Barnett BA, Heuberger AL, et al. (2013) Stool microbiome and metabolome differences between colorectal cancer patients and healthy adults. PLoS ONE 8: e70803 10.1371/journal.pone.0070803
    1. Vernia P, Marcheggiano A, Caprilli R, Frieri G, Corrao G, et al. (1995) Short-chain fatty acid topical treatment in distal ulcerative colitis. Aliment Pharmacol Ther 9: 309–313.
    1. Scheppach W, Sommer H, Kirchner T, Paganelli GM, Bartram P, et al. (1992) Effect of butyrate enemas on the colonic mucosa in distal ulcerative colitis. Gastroenterology 103: 51–56.
    1. Harig JM, Soergel KH, Komorowski RA, Wood CM (1989) Treatment of diversion colitis with short-chain-fatty acid irrigation. N Engl J Med 320: 23–28.
    1. Breuer RI, Soergel KH, Lashner BA, Christ ML, Hanauer SB, et al. (1997) Short chain fatty acid rectal irrigation for left-sided ulcerative colitis: a randomised, placebo controlled trial. Gut 40: 485–491.
    1. Patz J, Jacobsohn WZ, Gottschalk-Sabag S, Zeides S, Braverman DZ (1996) Treatment of refractory distal ulcerative colitis with short chain fatty acid enemas. Am J Gastroenterol 91: 731–734.
    1. Vieira EL, Leonel AJ, Sad AP, Beltrao NR, Costa TF, et al. (2012) Oral administration of sodium butyrate attenuates inflammation and mucosal lesion in experimental acute ulcerative colitis. J Nutr Biochem 23: 430–436. 10.1016/j.jnutbio.2011.01.007
    1. Haghikia A, Jorg S, Duscha A, Berg J, Manzel A, et al. (2015) Dietary Fatty Acids Directly Impact Central Nervous System Autoimmunity via the Small Intestine. Immunity 43: 817–829. 10.1016/j.immuni.2015.09.007
    1. Fröhlich EE, Mayerhofer R, Holzer P (2015) Reevaluating the hype: four bacterial metabolites under scrutiny. European Journal of Microbiology & Immunology 5: 1–13.
    1. Tremaroli V, Backhed F (2012) Functional interactions between the gut microbiota and host metabolism. Nature 489: 242–249. 10.1038/nature11552
    1. Lupton JR (2004) Microbial degradation products influence colon cancer risk: the butyrate controversy. J Nutr 134: 479–482.
    1. Donia MS, Fischbach MA (2015) Small Molecules from the Human Microbiota. Science 349(6246): 1254766(1–10). 10.1126/science.1254766
    1. Ridaura VK, Faith JJ, Rey FE, Cheng J, Duncan AE, et al. (2013) Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science 341(6150): 10.1126/science.1241214
    1. Kohl KD, Stengel A, Dearing MD (2015) Inoculation of tannin-degrading bacteria into novel hosts increases performance on tannin-rich diets. Environmental Microbiology 10.1111/1462-2920.12841
    1. den Besten G, van Eunen K, Groen AK, Venema K, Reijngoud DJ, et al. (2013) The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism. J Lipid Res 54: 2325–2340. 10.1194/jlr.R036012

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