The human microbiome project at ten years - some critical comments and reflections on “our third genome”, the human virome

Harald Brüssow

Microbiome Research Reports ›› 2023, Vol. 2 ›› Issue (1) : 7

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Microbiome Research Reports ›› 2023, Vol. 2 ›› Issue (1) :7 DOI: 10.20517/mrr.2022.20
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The human microbiome project at ten years - some critical comments and reflections on “our third genome”, the human virome

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Abstract

The Human Microbiome Project (HMP) has raised great expectations claiming the far-reaching influence of the microbiome on human health and disease ranging from obesity and malnutrition to effects going well beyond the gut. So far, with the notable exception of fecal microbiota transplantation in Clostridioides difficile infection, practical application of microbiome intervention has only achieved modest clinical effects. It is argued here that we need criteria for the link between microbiome and disease modelled on the links between pathogens and infectious disease in Koch’s postulates. The most important question is whether the microbiome change is a cause of the given disease or a consequence of a pathology leading to disease where the microbiome change is only a parallel event without a causal connection to the disease – in philosophical parlance, an epiphenomenon. Also discussed here is whether human virome research is a necessary complement to the microbiome project with a high potential for practical applications.

Keywords

Microbiome / disease / association / causation postulates / fecal transplantation / probiotics / bacteriophages / virome

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Harald Brüssow. The human microbiome project at ten years - some critical comments and reflections on “our third genome”, the human virome. Microbiome Research Reports, 2023, 2(1): 7 DOI:10.20517/mrr.2022.20

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References

[1]

Human microbiome project consortium. Structure, function and diversity of the healthy human microbiome.Nature2012;486:207-14 PMCID:PMC3564958

[2]

Ley R.The human microbiome: there is much left to do.Nature2022;606:435

[3]

Brüssow H.Problems with the concept of gut microbiota dysbiosis.Microb Biotechnol2020;13:423-34 PMCID:PMC7017827

[4]

Popper K Conjectures and refutations. The growth of scientific knowledge. Available from: https://books.google.com.hk/books/about/Conjectures_and_Refutations.html?id=IENmxiVBaSoC&redir_esc=y [Last accessed on 24 Mar 2023]

[5]

Subramanian S,Yatsunenko T.Persistent gut microbiota immaturity in malnourished Bangladeshi children.Nature2014;510:417-21 PMCID:PMC4189846

[6]

Raman AS,Venkatesh S.A sparse covarying unit that describes healthy and impaired human gut microbiota development.Science2019;365:eaau4735 PMCID:PMC6683326

[7]

Gehrig JL,Chang HW.Effects of microbiota-directed foods in gnotobiotic animals and undernourished children.Science2019;365:eaau4732 PMCID:PMC6683325

[8]

Chen RY,Hibberd MC.A microbiota-directed food intervention for undernourished children.N Engl J Med2021;384:1517-28

[9]

Vatanen T,Siegwald L.A distinct clade of bifidobacterium longum in the gut of bangladeshi children thrives during weaning.Cell2022;185:4280-4297.e12

[10]

A microbiota-directed food intervention for undernourished children. N Engl J Med 2022;386:1483-4.

[11]

Choudhury N,Hossain MI.Ready-to-use therapeutic food made from locally available food ingredients is well accepted by children having severe acute malnutrition in bangladesh.Food Nutr Bull2018;39:116-26

[12]

Lenters LM,Webb P,Bhutta ZA.Treatment of severe and moderate acute malnutrition in low- and middle-income settings: a systematic review, meta-analysis and Delphi process.BMC Public Health2013;13 Suppl 3:S23 PMCID:PMC3847503

[13]

Sultana S,Brüssow H.What happened to Koch's postulates in diarrhoea?.Environ Microbiol2017;19:2926-34

[14]

Brüssow H.What is health?.Microb Biotechnol2013;6:341-8

[15]

Gough E,Manges AR.Systematic review of intestinal microbiota transplantation (fecal bacteriotherapy) for recurrent Clostridium difficile infection.Clin Infect Dis2011;53:994-1002

[16]

Lee CH,Petrof EO.Frozen vs. fresh fecal microbiota transplantation and clinical resolution of diarrhea in patients with recurrent clostridium difficile infection: a randomized clinical trial.JAMA2016;315:142-9

[17]

Kelly CR,Staley C.Effect of fecal microbiota transplantation on recurrence in multiply recurrent clostridium difficile infection: a randomized trial.Ann Intern Med2016;165:609-16 PMCID:PMC5909820

[18]

Ott SJ,Rehman A.Efficacy of sterile fecal filtrate transfer for treating patients with clostridium difficile infection.Gastroenterology2017;152:799-811.e7

[19]

Li K,Zhou X.The mechanism of important components in canine fecal microbiota transplantation.Vet Sci2022;9:695 PMCID:PMC9786814

[20]

Zuo T,Lam K.Bacteriophage transfer during faecal microbiota transplantation in Clostridium difficile infection is associated with treatment outcome.Gut2018;67:634-43.

[21]

Smith AB,Keenan O.Enterococci enhance clostridioides difficile pathogenesis.Nature2022;611:780-6 PMCID:PMC9691601

[22]

Gerding, D. N., Johnson, S. Clostridium difficile infection, including pseudomembraneous colitis. Available from: https://accessmedicine.mhmedical.com/content.aspx?bookid=2129&sectionid=186949817 [Last accessed on 23 Mar 2023]

[23]

Moayyedi P,Kim PT.Fecal microbiota transplantation induces remission in patients with active ulcerative colitis in a randomized controlled trial.Gastroenterology2015;149:102-109.e6

[24]

Rossen NG,van der Spek MJ.Findings from a randomized controlled trial of fecal transplantation for patients with ulcerative colitis.Gastroenterology2015;149:110-118.e4

[25]

Paramsothy S,Kaakoush NO.Multidonor intensive faecal microbiota transplantation for active ulcerative colitis: a randomised placebo-controlled trial.Lancet2017;389:1218-28

[26]

Costello SP,Waters O.Effect of fecal microbiota transplantation on 8-week remission in patients with ulcerative colitis: a randomized clinical trial.JAMA2019;321:156-64 PMCID:PMC6439766

[27]

Caruso R,Núñez G.Host-microbiota interactions in inflammatory bowel disease.Nat Rev Immunol2020;20:411-26

[28]

Vaughn BP,Allegretti JR.Increased intestinal microbial diversity following fecal microbiota transplant for active Crohn's disease.Inflamm Bowel Dis2016;22:2182-90 PMCID:PMC4995064

[29]

Brüssow H.Turning the inside out: the microbiology of atopic dermatitis.Environ Microbiol2016;18:2089-102

[30]

Sharif S,Oddie SJ,McGuire W.Probiotics to prevent necrotising enterocolitis in very preterm or very low birth weight infants.Cochrane Database Syst Rev2020;10:CD005496.

[31]

Sharif S,Oddie SJ.Synbiotics to prevent necrotising enterocolitis in very preterm or very low birth weight infants.Cochrane Database Syst Rev2022;3:CD014067

[32]

Panigrahi P,Nanda NC.A randomized synbiotic trial to prevent sepsis among infants in rural India.Nature2017;548:407-12

[33]

Makrgeorgou A,Bath-Hextall FJ.Probiotics for treating eczema.Cochrane Database Syst Rev2018;11:CD006135.

[34]

Voigt J.Lactobacillus rhamnosus Used in the perinatal period for the prevention of atopic dermatitis in infants: a systematic review and meta-analysis of randomized trials.Am J Clin Dermatol2022;23:801-11 PMCID:PMC9576646

[35]

Norman JM,Baldridge MT.Disease-specific alterations in the enteric virome in inflammatory bowel disease.Cell2015;160:447-60 PMCID:PMC4312520

[36]

Lee CZ,Phipps ME.The gut virome in two indigenous populations from Malaysia.Sci Rep2022;12:1824 PMCID:PMC8813915

[37]

Garretto A,Wolfe AJ.Bacteriophages of the lower urinary tract.Nat Rev Urol2019;16:422-32 PMCID:PMC6800255

[38]

Zuo T,Zhang Y.Gut mucosal virome alterations in ulcerative colitis.Gut2019;68:1169-79 PMCID:PMC6582748

[39]

Gogokhia L,Bell R.Expansion of bacteriophages is linked to aggravated intestinal inflammation and colitis.Cell Host Microbe2019;25:285-299.e8 PMCID:PMC6885004

[40]

Clooney AG,Shkoporov AN.Whole-virome analysis sheds light on viral dark matter in inflammatory bowel disease.Cell Host Microbe2019;26:764-778.e5

[41]

Moreno-Gallego JL,Di Rienzi SC.Virome diversity correlates with intestinal microbiome diversity in adult monozygotic twins.Cell Host Microbe2019;25:261-272.e5 PMCID:PMC6411085

[42]

Furuse K,Kawashiro J.Bacteriophage distribution in human faeces: continuous survey of healthy subjects and patients with internal and leukaemic diseases.J Gen Virol1983;64:2039-43

[43]

Chibani-Chennoufi S,Bruttin A.Isolation of escherichia coli bacteriophages from the stool of pediatric diarrhea patients in bangladesh.J Bacteriol2004;186:8287-94 PMCID:PMC532420

[44]

Mathieu A,Deng L.Virulent coliphages in 1-year-old children fecal samples are fewer, but more infectious than temperate coliphages.Nat Commun2020;11:378 PMCID:PMC6969025

[45]

Schubbert R,Schmitz B.Foreign (M13) DNA ingested by mice reaches peripheral leukocytes, spleen, and liver via the intestinal wall mucosa and can be covalently linked to mouse DNA.Proc Natl Acad Sci U S A1997;94:961-6 PMCID:PMC19622

[46]

Bach MS,Khosravi A.Filamentous bacteriophage delays healing of pseudomonas-infected wounds.Cell Rep Med2022;3:100656 PMCID:PMC9244996

[47]

Sweere JM,Ishak H.Bacteriophage trigger antiviral immunity and prevent clearance of bacterial infection.Science2019;363 PMCID:PMC6656896

[48]

Merril CR,Petricciani JC.Bacterial virus gene expression in human cells.Nature1971;233:398-400

[49]

Carrera MR,Mee JM,Koob GF.Treating cocaine addiction with viruses.Proc Natl Acad Sci U S A2004;101:10416-21 PMCID:PMC478586

[50]

Popescu M,Khosravi A.Bacteriophages and the immune system.Annu Rev Virol2021;8:415-35

[51]

Miernikiewicz P.Endocytosis of bacteriophages.Curr Opin Virol2022;52:229-35

[52]

Barr JJ,Furlan M.Bacteriophage adhering to mucus provide a non-host-derived immunity.Proc Natl Acad Sci U S A2013;110:10771-6 PMCID:PMC3696810

[53]

Nguyen S,Padman BS.Bacteriophage Transcytosis Provides a Mechanism To Cross Epithelial Cell Layers. mBio 2017;8.

[54]

Górski A,Borysowski J.Phage as a modulator of immune responses: practical implications for phage therapy.Adv Virus Res83:41-71

[55]

Brüssow H,Hardt WD.Phages and the evolution of bacterial pathogens: from genomic rearrangements to lysogenic conversion.Microbiol Mol Biol Rev2004;68:560-602, table of contents PMCID:PMC515249

[56]

Canchaya C,Fournous G,Brüssow H.Prophage genomics.Microbiol Mol Biol Rev2003;67:238-76, table of contents PMCID:PMC156470

[57]

Brüssow H.Bacteria between protists and phages: from antipredation strategies to the evolution of pathogenicity.Mol Microbiol2007;65:583-9

[58]

Enault F,Bouteille L,Sullivan MB.Phages rarely encode antibiotic resistance genes: a cautionary tale for virome analyses.ISME J2017;11:237-47 PMCID:PMC5315482

[59]

Moon K,Kang I.Freshwater viral metagenome reveals novel and functional phage-borne antibiotic resistance genes.Microbiome2020;8:75 PMCID:PMC7265639

[60]

Blanco-Picazo P,Ramos-Barbero MD,Rodríguez-Rubio L.Dominance of phage particles carrying antibiotic resistance genes in the viromes of retail food sources.ISME J2023;17:195-203 PMCID:PMC9860054

[61]

Chen J,Chiang YN.Genome hypermobility by lateral transduction.Science2018;362:207-12

[62]

Fillol-Salom A,Humphrey S,Chen J.Lateral transduction is inherent to the life cycle of the archetypical salmonella phage P22.Nat Commun2021;12:6510 PMCID:PMC8575938

[63]

Sulakvelidze A,Morris JG Jr.Bacteriophage therapy.Antimicrob Agents Chemother2001;45:649-59 PMCID:PMC90351

[64]

Sarker SA,Reuteler G.Oral phage therapy of acute bacterial diarrhea with two coliphage preparations: a randomized trial in children from bangladesh.EBioMedicine2016;4:124-37 PMCID:PMC4776075

[65]

Leitner L,Chanishvili N.Intravesical bacteriophages for treating urinary tract infections in patients undergoing transurethral resection of the prostate: a randomised, placebo-controlled, double-blind clinical trial.Lancet Infect Dis2021;21:427-36

[66]

Jault P,Jennes S.Efficacy and tolerability of a cocktail of bacteriophages to treat burn wounds infected by pseudomonas aeruginosa: a randomised, controlled, double-blind phase 1/2 trial.Lancet Infect Dis2019;19:35-45

[67]

Wright A,Anggård EE.A controlled clinical trial of a therapeutic bacteriophage preparation in chronic otitis due to antibiotic-resistant Pseudomonas aeruginosa; a preliminary report of efficacy.Clin Otolaryngol2009;34:349-57

[68]

Aslam S,Wooten D.Lessons learned from the first 10 consecutive cases of intravenous bacteriophage therapy to treat multidrug-resistant bacterial infections at a single center in the united states.Open Forum Infect Dis2020;7:ofaa389 PMCID:PMC7519779

[69]

Dedrick RM,Cristinziano M.Phage therapy of mycobacterium infections: compassionate use of phages in 20 patients with drug-resistant mycobacterial disease.Clin Infect Dis2023;76:103-12 PMCID:PMC9825826

[70]

Doub JB,Nandi S.Experience using adjuvant bacteriophage therapy for the treatment of 10 recalcitrant periprosthetic joint infections: a case series.Clin Infect Dis2023;76:e1463-6

[71]

Fabijan A, Lin RCY, Ho J, Maddocks S, Ben Zakour NL, Iredell JR; Westmead bacteriophage therapy team. safety of bacteriophage therapy in severe staphylococcus aureus infection.Nat Microbiol2020;5:465-72

[72]

Eskenazi A,Wubbolts J.Combination of pre-adapted bacteriophage therapy and antibiotics for treatment of fracture-related infection due to pandrug-resistant Klebsiella pneumoniae.Nat Commun2022;13:302 PMCID:PMC8766457

[73]

Dedrick RM,Garlena RA.Engineered bacteriophages for treatment of a patient with a disseminated drug-resistant Mycobacterium abscessus.Nat Med2019;25:730-3 PMCID:PMC6557439

[74]

Friman VP,Sierocinski P.Pre-adapting parasitic phages to a pathogen leads to increased pathogen clearance and lowered resistance evolution with Pseudomonas aeruginosa cystic fibrosis bacterial isolates.J Evol Biol2016;29:188-98

[75]

Dunne M,Loessner MJ.Reprogramming bacteriophage host range: design principles and strategies for engineering receptor binding proteins.Curr Opin Biotechnol2021;68:272-81

[76]

Federici S,Valdés-Mas R.Targeted suppression of human IBD-associated gut microbiota commensals by phage consortia for treatment of intestinal inflammation.Cell2022;185:2879-2898.e24

[77]

Atarashi K,Luo C.Ectopic colonization of oral bacteria in the intestine drives T(H)1 cell induction and inflammation.Science2017;358:359-65 PMCID:PMC5682622

[78]

Bertocchi A.A viral cocktail calms gut inflammation.Nature2022;612:220-1

[79]

Barrangou R,Deveau H.CRISPR provides acquired resistance against viruses in prokaryotes.Science2007;315:1709-12

[80]

Al-Shayeb B,Soczek KM.Diverse virus-encoded CRISPR-cas systems include streamlined genome editors.Cell2022;185:4574-4586.e16

[81]

Leavitt A,Amitai G.Viruses inhibit TIR gcADPR signalling to overcome bacterial defence.Nature2022;611:326-31

[82]

Jebb D,Pippel M.Six reference-quality genomes reveal evolution of bat adaptations.Nature2020;583:578-84 PMCID:PMC8075899

[83]

Tisza MJ,Welch NL.Discovery of several thousand highly diverse circular DNA viruses.Elife2020;9 PMCID:PMC7000223

[84]

Kaczorowska J.Human anelloviruses: diverse, omnipresent and commensal members of the virome.FEMS Microbiol Rev2020;44:305-13 PMCID:PMC7326371

[85]

Virgin HW,Ahmed R.Redefining chronic viral infection.Cell2009;138:30-50

[86]

Cuicchi D,Tardio ML.Virological and histological evaluation of intestinal samples in COVID-19 patients.World J Gastroenterol2022;28:6282-93 PMCID:PMC9730443

[87]

Wölfel R,Guggemos W.Virological assessment of hospitalized patients with COVID-2019.Nature2020;581:465-9.

[88]

Vogel G.Signals from the sewer.Science2022;375:1100-4

[89]

Bowes DA,Kraberger S.Leveraging an established neighbourhood-level, open access wastewater monitoring network to address public health priorities: a population-based study.Lancet Microbe2023;4:e29-37 PMCID:PMC9725778

[90]

Peccia J,Brackney DE.Measurement of SARS-CoV-2 RNA in wastewater tracks community infection dynamics.Nat Biotechnol2020;38:1164-7 PMCID:PMC8325066

[91]

Ryerson AB,Alazawi MA.2022 US. poliovirus response team. wastewater testing and detection of poliovirus type 2 genetically linked to virus isolated from a paralytic polio case - New York, March 9-October 11, 2022.MMWR Morb Mortal Wkly Rep2022;71:1418-24

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