The keystone-pathogen hypothesis

Hajishengallis, George; Darveau, Richard P.; Curtis, Michael A.

doi:10.1038/nrmicro2873

Cited by 1,790Gut microbiota and healthOral microbiology and periodontitis researchBacterial biofilms and quorum sensing

The keystone-pathogen hypothesis

Open access

Hajishengallis, George, Darveau, Richard P., Curtis, Michael A.·2012·Nature Reviews Microbiology

DOI 10.1038/nrmicro2873PMC PMC3498498

Open this paper in CoChat — free account

Abstract

Recent studies have highlighted the importance of the human microbiome in health and disease. However, for the most part the mechanisms by which the microbiome mediates disease, or protection from it, remain poorly understood. The keystone-pathogen hypothesis holds that certain low-abundance microbial pathogens can orchestrate inflammatory disease by remodelling a normally benign microbiota into a dysbiotic one. In this Opinion article, we critically assess the available literature that supports this hypothesis, which may provide a novel conceptual basis for the development of targeted diagnostics and treatments for complex dysbiotic diseases.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1038/nrmicro2873

Cites

86 of 86 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

The genus Prevotella, including P. denticola, acts on the early and middle steps of oral biofilm formation with cellular adhesion for later colonizers and supports the biofilm formation of Aggregatibacter actinomycetemcomitans.
“The genus Prevotella, including P. denticola, acts on the early and middle steps of oral biofilm formation with cellular adhesion for later colonizers and, in particular, supports the biofilm formation of Aggregatibacter actinomycetemcomitans [22,23].”
From Analysis of Chemical Structure and Antibiofilm Properties of Exopolysaccharides from Lactiplantibacillus plantarum EIR/IF-1 Postbiotics (2022) · cites this paper as [22]
The section “Periodontitis and keystone pathogen-induced dysbiosis” discusses Porphyromonas gingivalis and changes in oral biofilms, not a role for Prevotella denticola in adhesion or early-to-middle biofilm formation. Searches for Prevotella denticola and Aggregatibacter actinomycetemcomitans found no passage in our copy supporting the claimed interaction; related species appear only in the References. No page numbers were available for these passages. (LLM, conf=0.76)
Experimental — accuracy not yet measured
The keystone-pathogen hypothesis and the α-bug hypothesis both state that certain low abundance microbiota members, such as enterotoxigenic B. fragilis, possess unique virulence traits that are pro-oncogenic and remodel the microbiome, promoting mucosal immune responses and colonic epithelial cell changes.
“The keystone-pathogen hypothesis88 and the α-bug hypothesis both state that certain, low abundance microbiota members (such as enterotoxigenic B. fragilis) possess unique virulence traits, which are pro-oncogenic and remodel the microbiome and in turn promote mucosal immune responses and colonic epithelial cell changes.89”
From The gut microbiota and host health: a new clinical frontier (2016) · cites this paper as [88]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

A human gut microbial gene catalogue established by metagenomic sequencing
MetaHIT Consortium, Qin, J., Li, R., Raes, J., Arumugam, M., Burgdorf, K. S., Manichanh, C., Nielsen, T., Pons, N., Levenez, F., et al. (2010) · Nature · doi:10.1038/nature08821 · Cited by 11,624 · see citing works
Enterotypes of the human gut microbiome
MetaHIT Consortium (additional members), Arumugam, M., Raes, J., Pelletier, E., Le Paslier, D., Yamada, T., Mende, D. R., Fernandes, G. R., Tap, J., Bruls, T., et al. (2011) · Nature · doi:10.1038/nature09944 · Cited by 7,548 · see citing works
Food Web Complexity and Species Diversity
Paine, R. T. (1966) · The American Naturalist · doi:10.1086/282400 · Cited by 5,361 · see citing works
Host-Bacterial Mutualism in the Human Intestine
Bäckhed, F., Ley, R. E., Sonnenburg, J. L., Peterson, D. A., & Gordon, J. I. (2005) · Science · doi:10.1126/science.1104816 · Cited by 5,277 · see citing works
Microbial complexes in subgingival plaque
Socransky, S. S., Haffajee, A. D., Cugini, M. A., Smith, C., & Kent, R. L. (1998) · Journal of Clinical Periodontology · doi:10.1111/j.1600-051x.1998.tb02419.x · Cited by 5,050 · see citing works
Periodontal diseases
Pihlstrom, B. L., Michalowicz, B. S., & Johnson, N. W. (2005) · The Lancet · doi:10.1016/s0140-6736(05)67728-8 · Cited by 3,718 · see citing works
A microbial symbiosis factor prevents intestinal inflammatory disease
Mazmanian, S. K., Round, J. L., & Kasper, D. L. (2008) · Nature · doi:10.1038/nature07008 · Cited by 2,340 · see citing works
Metabolic Syndrome and Altered Gut Microbiota in Mice Lacking Toll-Like Receptor 5
Vijay-Kumar, M., Aitken, J. D., Carvalho, F. A., Cullender, T. C., Mwangi, S., Srinivasan, S., Sitaraman, S. V., Knight, R., Ley, R. E., & Gewirtz, A. T. (2010) · Science · doi:10.1126/science.1179721 · Cited by 2,068 · see citing works
Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma
Castellarin, M., Warren, R. L., Freeman, J. D., Dreolini, L., Krzywinski, M., Strauss, J., Barnes, R., Watson, P., Allen-Vercoe, E., Moore, R. A., et al. (2012) · Genome Research · doi:10.1101/gr.126516.111 · Cited by 2,043 · see citing works
NLRP6 Inflammasome Regulates Colonic Microbial Ecology and Risk for Colitis
Elinav, E., Strowig, T., Kau, A. L., Henao-Mejia, J., Thaiss, C. A., Booth, C. J., Peaper, D. R., Bertin, J., Eisenbarth, S. C., Gordon, J. I., et al. (2011) · Cell · doi:10.1016/j.cell.2011.04.022 · Cited by 2,024 · see citing works
Challenges in the Quest for Keystones
Power, M. E., Tilman, D., Estes, J. A., Menge, B. A., Bond, W. J., Mills, L. S., Daily, G., Castilla, J. C., Lubchenco, J., & Paine, R. T. (1996) · BioScience · doi:10.2307/1312990 · Cited by 2,018 · see citing works
Genomic analysis identifies association of Fusobacterium with colorectal carcinoma
Kostic, A. D., Gevers, D., Pedamallu, C. S., Michaud, M., Duke, F., Earl, A. M., Ojesina, A. I., Jung, J., Bass, A. J., Tabernero, J., et al. (2012) · Genome Research · doi:10.1101/gr.126573.111 · Cited by 1,960 · see citing works
Human gut microbiota in obesity and after gastric bypass
Zhang, H., DiBaise, J. K., Zuccolo, A., Kudrna, D., Braidotti, M., Yu, Y., Parameswaran, P., Crowell, M. D., Wing, R., Rittmann, B. E., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0812600106 · Cited by 1,880 · see citing works
Intestinal homeostasis and its breakdown in inflammatory bowel disease
Maloy, K. J., & Powrie, F. M. (2011) · Nature · doi:10.1038/nature10208 · Cited by 1,876 · see citing works
A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17 T cell responses
Wu, S., Rhee, K.-J., Albesiano, E., Rabizadeh, S., Wu, X., Yen, H.-R., Huso, D. L., Brancati, F. L., Wick, E., McAllister, F., et al. (2009) · Nature Medicine · doi:10.1038/nm.2015 · Cited by 1,812 · see citing works
Crosstalk between cancer and immune cells: role of STAT3 in the tumour microenvironment
Yu, H., Kortylewski, M., & Pardoll, D. M. (2006) · Nature reviews. Immunology · doi:10.1038/nri1995 · Cited by 1,809 · see citing works
A note on trophic complexity and community stability.
Paine, R. T. (1969) · The American Naturalist · doi:10.1086/282586 · Cited by 1,796 · see citing works
Periodontitis: a polymicrobial disruption of host homeostasis
Darveau, R. P. (2010) · Nature Reviews Microbiology · doi:10.1038/nrmicro2337 · Cited by 1,688 · see citing works
Self-citation
H OW H OST -M ICROBIAL I NTERACTIONS S HAPE THE N UTRIENT E NVIRONMENT OF THE M AMMALIAN I NTESTINE
Hooper, L. V., Midtvedt, T., & Gordon, J. I. (2002) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.22.011602.092259 · Cited by 1,623 · see citing works
The Toll-like receptor 2 pathway establishes colonization by a commensal of the human microbiota
Round, J. L., Lee, S. M., Li, J., Tran, G., Jabri, B., Chatila, T. A., & Mazmanian, S. K. (2011) · Science · doi:10.1126/science.1206095 · Cited by 1,604 · see citing works
A Genomic View of the Human- Bacteroides thetaiotaomicron Symbiosis
Xu, J., Bjursell, M. K., Himrod, J., Deng, S., Carmichael, L. K., Chiang, H. C., Hooper, L. V., & Gordon, J. I. (2003) · Science · doi:10.1126/science.1080029 · Cited by 1,353 · see citing works
Host-Mediated Inflammation Disrupts the Intestinal Microbiota and Promotes the Overgrowth of Enterobacteriaceae
Lupp, C., Robertson, M. L., Wickham, M. E., Sekirov, I., Champion, O. L., Gaynor, E. C., & Finlay, B. B. (2007) · Cell Host & Microbe · doi:10.1016/j.chom.2007.06.010 · Cited by 1,310 · see citing works
Sea Otters: Their Role in Structuring Nearshore Communities
Estes, J. A., & Palmisano, J. F. (1974) · Science · doi:10.1126/science.185.4156.1058 · Cited by 1,187 · see citing works
Glycan foraging in vivo by an intestine-adapted bacterial symbiont
Sonnenburg, J. L., Xu, J., Leip, D. D., Chen, C.-H., Westover, B. P., Weatherford, J., Buhler, J. D., & Gordon, J. I. (2005) · Science · doi:10.1126/science.1109051 · Cited by 1,184 · see citing works
Low-Abundance Biofilm Species Orchestrates Inflammatory Periodontal Disease through the Commensal Microbiota and Complement
Hajishengallis, G., Liang, S., Payne, M. A., Hashim, A., Jotwani, R., Eskan, M. A., McIntosh, M. L., Alsam, A., Kirkwood, K. L., Lambris, J. D., et al. (2011) · Cell Host & Microbe · doi:10.1016/j.chom.2011.10.006 · Cited by 1,154 · see citing works
Self-citation
Epithelial-cell recognition of commensal bacteria and maintenance of immune homeostasis in the gut
Artis, D. (2008) · Nature reviews. Immunology · doi:10.1038/nri2316 · Cited by 1,136 · see citing works
Diabetes mellitus and periodontitis: a tale of two common interrelated diseases
Lalla, E., & Papapanou, P. N. (2011) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2011.106 · Cited by 1,063 · see citing works
Salmonella enterica serovar typhimurium exploits inflammation to compete with the intestinal microbiota
Stecher, B., Robbiani, R., Walker, A. W., Westendorf, A. M., Barthel, M., Kremer, M., Chaffron, S., Macpherson, A. J., Buer, J., Parkhill, J., et al. (2007) · PLoS Biology · doi:10.1371/journal.pbio.0050244 · Cited by 1,048 · see citing works
Commensal anaerobic gut bacteria attenuate inflammation by regulating nuclear-cytoplasmic shuttling of PPAR-γ and RelA
Kelly, D., Campbell, J. I., King, T. P., Grant, G., Jansson, E. Å., Coutts, A., Pettersson, S., & Conway, S. (2003) · Nature Immunology · doi:10.1038/ni1018 · Cited by 997 · see citing works
Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia: the ‘red complex’, a prototype polybacterial pathogenic consortium in periodontitis
Holt, S. C., & Ebersole, J. L. (2005) · Periodontology 2000 · doi:10.1111/j.1600-0757.2005.00113.x · Cited by 932 · see citing works
Angiogenins: a new class of microbicidal proteins involved in innate immunity
Hooper, L. V., Stappenbeck, T. S., Hong, C. V., & Gordon, J. I. (2003) · Nature Immunology · doi:10.1038/ni888 · Cited by 929 · see citing works
Communicable Ulcerative Colitis Induced by T-bet Deficiency in the Innate Immune System
Garrett, W. S., Lord, G. M., Punit, S., Lugo‐Villarino, G., Mazmanian, S. K., Ito, S., Glickman, J. N., & Glimcher, L. H. (2007) · Cell · doi:10.1016/j.cell.2007.08.017 · Cited by 918 · see citing works
Monitoring Bacterial Community of Human Gut Microbiota Reveals an Increase in Lactobacillus in Obese Patients and Methanogens in Anorexic Patients
Armougom, F., Henry, M., Vialettes, B., Raccah, D., & Raoult, D. (2009) · PLoS ONE · doi:10.1371/journal.pone.0007125 · Cited by 905 · see citing works
A bacterial driver–passenger model for colorectal cancer: beyond the usual suspects
Tjalsma, H., Boleij, A., Marchesi, J. R., & Dutilh, B. E. (2012) · Nature Reviews Microbiology · doi:10.1038/nrmicro2819 · Cited by 903 · see citing works
Escherichia coli induces DNA damage in vivo and triggers genomic instability in mammalian cells
Cuevas-Ramos, G., Petit, C. R., Marcq, I., Boury, M., Oswald, E., & Nougayrède, J.-P. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1001261107 · Cited by 855 · see citing works
Enterobacteriaceae Act in Concert with the Gut Microbiota to Induce Spontaneous and Maternally Transmitted Colitis
Garrett, W. S., Gallini, C. A., Yatsunenko, T., Michaud, M., DuBois, A., Delaney, M. L., Punit, S., Karlsson, M., Bry, L., Glickman, J. N., et al. (2010) · Cell Host & Microbe · doi:10.1016/j.chom.2010.08.004 · Cited by 788 · see citing works
Enhanced Escherichia coli adherence and invasion in Crohn’s disease and colon cancer 1 1The authors thank Professor T. K. Korhonen (Division of General Microbiology, University of Helsinki, Finland), who kindly donated Escherichia coli IH11165; Professor J.-F. Colombel (Laboratoire de Recherche sur les Maladies Inflammatoire de l’Intestine, Centre Hospitalier Universitaire, Lille, France) and Professor A. Darfeuille-Michaud (Faculte de Pharmacie, Clermont-Ferrand, France), who kindly donated the Crohn’s disease ileal isolates LF10 and LF82; and Dr. Keith Leiper (Gastroenterology Unit, Royal Liverpool & Broadgreen University Hospitals Trust, Liverpool, UK) for his cooperation in obtaining colorectal tissue specimens.As a consequence of the work described herein, a patent application has been filed by the University of Liverpool regarding the use of soluble plantain fiber in Crohn’s disease.
Martin, H., Campbell, B. J., Hart, C. A., Mpofu, C., Nayar, M. K., Singh, R., Englyst, H. N., Williams, H. F., & Rhodes, J. M. (2004) · Gastroenterology · doi:10.1053/j.gastro.2004.03.054 · Cited by 719 · see citing works
A humanized gnotobiotic mouse model of host-archaeal-bacterial mutualism
Samuel, B. S., & Gordon, J. I. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0602187103 · Cited by 674 · see citing works
Intestinal Microbiota Promote Enteric Virus Replication and Systemic Pathogenesis
Kuss-Duerkop, S. K., Best, G. T., Etheredge, C. A., Pruijssers, A. J. P., Frierson, J. M., Hooper, L. V., Dermody, T. S., & Pfeiffer, J. K. (2011) · Science · doi:10.1126/science.1211057 · Cited by 631 · see citing works
Microbiology of Periodontal Disease—Present Status and Future Considerations
Socransky, S. S. (1977) · Journal of Periodontology · doi:10.1902/jop.1977.48.9.497 · Cited by 629 · see citing works
Genomic and metabolic adaptations of Methanobrevibacter smithii to the human gut
Samuel, B. S., Hansen, E. E., Manchester, J. K., Coutinho, P. M., Henrissat, B., Fulton, R., Latreille, P., Kim, K., Wilson, R. K., & Gordon, J. I. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0704189104 · Cited by 549 · see citing works
Role of the Commensal Microbiota in Normal and Pathogenic Host Immune Responses
Littman, D. R., & Pamer, E. G. (2011) · Cell Host & Microbe · doi:10.1016/j.chom.2011.10.004 · Cited by 548 · see citing works
Bacteriology of severe periodontitis in young adult humans
Moore, W. E., Holdeman, L. V., Smibert, R. M., Hash, D. E., Burmeister, J. A., & Ranney, R. R. (1982) · Infection and Immunity · doi:10.1128/iai.38.3.1137-1148.1982 · Cited by 480 · see citing works
Implantation of Bacteroides gingivalis in Nonhuman Primates Initiates Progression of Periodontitis
Holt, S. C., Ebersole, J. L., Felton, J. R., Brunsvold, M. A., & Kornman, K. S. (1988) · Science · doi:10.1126/science.3336774 · Cited by 464 · see citing works
Resolvin E1 Regulates Inflammation at the Cellular and Tissue Level and Restores Tissue Homeostasis In Vivo
Hastürk, H., Kantarcı, A., Goguet, E., Blackwood, A., Andry, C., Serhan, C. N., & Dyke, T. E. V. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.10.7021 · Cited by 462 · see citing works
A possible role of Bacteroides fragilis enterotoxin in the aetiology of colorectal cancer
Ulger Toprak, N., Yagci, A., Gulluoglu, B. M., Akin, M. L., Demirkalem, P., Celenk, T., & Soyletir, G. (2006) · Clinical Microbiology and Infection · doi:10.1111/j.1469-0691.2006.01494.x · Cited by 454 · see citing works
Pathobionts of the gastrointestinal microbiota and inflammatory disease
Chow, J., Tang, H., & Mazmanian, S. K. (2011) · Current Opinion in Immunology · doi:10.1016/j.coi.2011.07.010 · Cited by 445 · see citing works
The Commensal Microbiota and Enteropathogens in the Pathogenesis of Inflammatory Bowel Diseases
Chassaing, B., & Darfeuille–Michaud, A. (2011) · Gastroenterology · doi:10.1053/j.gastro.2011.01.054 · Cited by 443 · see citing works
The leukocyte integrin antagonist Del-1 inhibits IL-17-mediated inflammatory bone loss
Eskan, M. A., Jotwani, R., Abe, T., Chmelar, J., Lim, J.-H., Liang, S., Ciero, P. A., Krauss, J. L., Li, F., Rauner, M., et al. (2012) · Nature Immunology · doi:10.1038/ni.2260 · Cited by 429 · see citing works
Self-citation
Modulation of the Intestinal Microbiota Alters Colitis-Associated Colorectal Cancer Susceptibility
Uronis, J. M., Mühlbauer, M., Herfarth, H. H., Rubinas, T. C., Jones, G. S., & Jobin, C. (2009) · PLoS ONE · doi:10.1371/journal.pone.0006026 · Cited by 425 · see citing works
Enterotoxigenic Bacteroides fragilis : a Rogue among Symbiotes
Sears, C. L. (2009) · Clinical Microbiology Reviews · doi:10.1128/cmr.00053-08 · Cited by 412 · see citing works
Gastrointestinal microbiology enters the metagenomics era
Frank, D. N., & Pace, N. R. (2008) · Current Opinion in Gastroenterology · doi:10.1097/mog.0b013e3282f2b0e8 · Cited by 405 · see citing works
The impact of the microbiota on the pathogenesis of IBD: lessons from mouse infection models
Nell, S., Suerbaum, S., & Josenhans, C. (2010) · Nature Reviews Microbiology · doi:10.1038/nrmicro2403 · Cited by 396 · see citing works
Bacteroides fragilis enterotoxin induces c-Myc expression and cellular proliferation
Wu, S., Morin, P. J., Maouyo, D., & Sears, C. L. (2003) · Gastroenterology · doi:10.1053/gast.2003.50047 · Cited by 396 · see citing works
Successful Transmission of a Retrovirus Depends on the Commensal Microbiota
Kane, M., Case, L. K., Kopaskie, K., Kozlova, A., MacDearmid, C., Chervonsky, A. V., & Golovkina, T. V. (2011) · Science · doi:10.1126/science.1210718 · Cited by 360 · see citing works
Periodontitis in RA—the citrullinated enolase connection
Lundberg, K., Wegner, N., Yucel‐Lindberg, T., & Venables, P. J. (2010) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2010.139 · Cited by 344 · see citing works
Local Chemokine Paralysis, a Novel Pathogenic Mechanism forPorphyromonas gingivalis
Darveau, R. P., Belton, C. M., Reife, R. A., & Lamont, R. J. (1998) · Infection and Immunity · doi:10.1128/iai.66.4.1660-1665.1998 · Cited by 343 · see citing works
Self-citation
A New Inflammatory Cytokine on the Block: Re-thinking Periodontal Disease and the Th1/Th2 Paradigm in the Context of Th17 Cells and IL-17
Gaffen, S. L., & Hajishengallis, G. (2008) · Journal of Dental Research · doi:10.1177/154405910808700908 · Cited by 334 · see citing works
Self-citation
Changes in Periodontal Health Status Are Associated with Bacterial Community Shifts as Assessed by Quantitative 16S Cloning and Sequencing
Kumar, P., Leys, E. J., Bryk, J., Martinez, F. J., Moeschberger, M. L., & Griffen, A. L. (2006) · Journal of Clinical Microbiology · doi:10.1128/jcm.00317-06 · Cited by 318 · see citing works
Microbial manipulation of receptor crosstalk in innate immunity
Hajishengallis, G., & Lambris, J. D. (2011) · Nature reviews. Immunology · doi:10.1038/nri2918 · Cited by 307 · see citing works
Self-citation
A Pathobiont of the Microbiota Balances Host Colonization and Intestinal Inflammation
Chow, J., & Mazmanian, S. K. (2010) · Cell Host & Microbe · doi:10.1016/j.chom.2010.03.004 · Cited by 292 · see citing works
The microflora of periodontal sites showing active destructive progression
Moore, W. E., Moore, L. H., Ranney, R. R., Smibert, R. M., Burmeister, J. A., & Schenkein, H. A. (1991) · Journal Of Clinical Periodontology · doi:10.1111/j.1600-051x.1991.tb00064.x · Cited by 265 · see citing works
Perspective: Alpha-Bugs, Their Microbial Partners, and the Link to Colon Cancer
Sears, C. L., & Pardoll, D. M. (2011) · The Journal of Infectious Diseases · doi:10.1093/jinfdis/jiq061 · Cited by 259 · see citing works
The intestinal microbiota, gastrointestinal environment and colorectal cancer: a putative role for probiotics in prevention of colorectal cancer?
Azcárate-Peril, M. A., Sikes, M. L., & Bruno-Bárcena, J. M. (2011) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00110.2011 · Cited by 252 · see citing works
Microbial Hijacking of Complement–Toll-Like Receptor Crosstalk
Wang, M., Krauss, J. L., Domon, H., Hosur, K. B., Liang, S., Magotti, P., Triantafilou, M., Triantafilou, K., Lambris, J. D., & Hajishengallis, G. (2010) · Science Signaling · doi:10.1126/scisignal.2000697 · Cited by 228 · see citing works
Self-citation
Reducing the risk of CVD in patients with periodontitis
Genco, R. J., & Van Dyke, T. E. (2010) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2010.120 · Cited by 182 · see citing works
The C5a Receptor Impairs IL-12–Dependent Clearance of Porphyromonas gingivalis and Is Required for Induction of Periodontal Bone Loss
Liang, S., Krauss, J. L., Domon, H., McIntosh, M. L., Hosur, K. B., Qu, H., Li, F., Τζέκου, Α., Lambris, J. D., & Hajishengallis, G. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.1003252 · Cited by 173 · see citing works
Self-citation
Linking Keystone Species and Functional Groups: A New Operational Definition of the Keystone Species Concept
Davic, R. D. (2003) · Conservation Ecology · doi:10.5751/es-00502-0701r11 · Cited by 164 · see citing works
The Oral Microbial Consortium's Interaction with the Periodontal Innate Defense System
Darveau, R. P. (2009) · DNA and Cell Biology · doi:10.1089/dna.2009.0864 · Cited by 150 · see citing works
Self-citation
Attaching and Effacing Escherichia coli Downregulate DNA Mismatch Repair Protein In Vitro and Are Associated with Colorectal Adenocarcinomas in Humans
Maddocks, O. D. K., Short, A., Donnenberg, M. S., Bader, S. A., & Harrison, D. J. (2009) · PLoS ONE · doi:10.1371/journal.pone.0005517 · Cited by 150 · see citing works
Community-Wide Response of the Gut Microbiota to Enteropathogenic Citrobacter rodentium Infection Revealed by Deep Sequencing
Hoffmann, C., Hill, D. A., Minkah, N., Kirn, T., Troy, A., Artis, D., & Bushman, F. (2009) · Infection and Immunity · doi:10.1128/iai.00493-09 · Cited by 142 · see citing works
Inflammation and Cancer. I. Rodent models of infectious gastrointestinal and liver cancer.
Rogers, A., & Fox, J. (2004) · American Journal of Physiology - Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00499.2003 · Cited by 137 · see citing works
Porphyromonas gingivalis infection of oral epithelium inhibits neutrophil transepithelial migration
Madianos, P., Papapanou, P. N., & Sandros, J. (1997) · Infection and Immunity · doi:10.1128/iai.65.10.3983-3990.1997 · Cited by 124 · see citing works
Persistent bacterial colonization of Porphyromonas gingivalis, Prevotella intermedia, and Actinobacillus actinomycetemcomitans in periodontitis and its association with alveolar bone loss after 6 months of therapy
Chaves, E. S., Jeffcoat, M. K., Ryerson, C. C., & Snyder, B. (2000) · Journal Of Clinical Periodontology · doi:10.1034/j.1600-051x.2000.027012897.x · Cited by 111 · see citing works
Sporadic colorectal cancer – role of the commensal microbiota
Hope, M. E., Hold, G. L., Kain, R., & El-Omar, E. M. (2005) · FEMS Microbiology Letters · doi:10.1016/j.femsle.2005.01.029 · Cited by 109 · see citing works
Effect of Periodontal Pathogens on the Metatranscriptome of a Healthy Multispecies Biofilm Model
Frias‐Lopez, J., & Duran-Pinedo, A. E. (2012) · Journal of Bacteriology · doi:10.1128/jb.06328-11 · Cited by 97 · see citing works
Nuclear factor-kappa B activation pathway in intestinal epithelial cells is a major regulator of chemokine gene expression and neutrophil migration induced byBacteroides fragilisenterotoxin
Kim, J. M., CHO, S. J., Oh, Y., JUNG, H.-Y., Kim, Y.-J., & KIM, N. (2002) · Clinical & Experimental Immunology · doi:10.1046/j.1365-2249.2002.01921.x · Cited by 88 · see citing works
Methanogens outcompete sulphate reducing bacteria for H2 in the human colon.
Strocchi, A., Furne, J. K., Ellis, C., & Levitt, M. D. (1994) · Gut · doi:10.1136/gut.35.8.1098 · Cited by 86 · see citing works
CD4+-T-Cell Effector Functions and Costimulatory Requirements Essential for Surviving Mucosal Infection with Citrobacter rodentium
Bry, L., Brigl, M., & Brenner, M. (2006) · Infection and Immunity · doi:10.1128/iai.74.1.673-681.2006 · Cited by 81 · see citing works
Role of Porphyromonas gingivalis Phosphoserine Phosphatase Enzyme SerB in Inflammation, Immune Response, and Induction of Alveolar Bone Resorption in Rats
Bainbridge, B. W., Verma, R. K., Eastman, C., Yehia, B., Rivera, M. F., Moffatt, C. E., Bhattacharyya, I., Lamont, R. J., & Kesavalu, L. N. (2010) · Infection and Immunity · doi:10.1128/iai.00703-10 · Cited by 69 · see citing works
Enumeration of Porphyromonas gingivalis, Prevotella intermedia and Actinobacillus actinomycetemcomitans in subgingival plaque samples by a quantitative-competitive PCR method
Doungudomdacha, S., Rawlinson, Ā., & Douglas, C. W. I. (2000) · Journal of Medical Microbiology · doi:10.1099/0022-1317-49-10-861 · Cited by 62 · see citing works
Immunization of Macaca fascicularis against experimental periodontitis using a vaccine containing cysteine proteases purified from Porphyromonas gingivalis
Page, R. C., Lantz, M. S., Darveau, R. P., Jeffcoat, M. K., Mancl, L., Houston, L. S., Braham, P. H., & Persson, G. R. (2007) · Oral Microbiology and Immunology · doi:10.1111/j.1399-302x.2007.00337.x · Cited by 51 · see citing works
Self-citation
Porphyromonas gingivalis Sinks Teeth into the Oral Microbiota and Periodontal Disease
Honda, K. (2011) · Cell Host & Microbe · doi:10.1016/j.chom.2011.10.008 · Cited by 46 · see citing works
Enterotoxigenic Bacteroides fragilis
Holton, J. (2008) · Current Infectious Disease Reports · doi:10.1007/s11908-008-0018-7 · Cited by 29 · see citing works
Say hello to our little friends
Walker, A. W. (2007) · Nature Reviews Microbiology · doi:10.1038/nrmicro1720 · Cited by 24 · see citing works
11. Community and Ecosystem Impacts of Single-Species Extinctions
Simberloff, D. (2003) · Princeton University Press eBooks · doi:10.1515/9781400866779-016 · Cited by 4 · see citing works

Flagged first, then by citations

Sorted by citations

Periodontitis: from microbial immune subversion to systemic inflammation
Hajishengallis, G. (2015) · Nature Reviews Immunology · doi:10.1038/nri3785 · Cited by 3,046 · see citing works
Self-citation
Keystone taxa as drivers of microbiome structure and functioning
Banerjee, S., Schlaeppi, K., & van der Heijden, M. G. A. (2018) · Nature Reviews Microbiology · doi:10.1038/s41579-018-0024-1 · Cited by 3,044 · see citing works
The gut microbiota and host health: a new clinical frontier
Marchesi, J. R., Adams, D. H., Fava, F., Hermes, G. D. A., Hirschfield, G. M., Hold, G., Quraishi, M. N., Kinross, J., Smidt, H., Tuohy, K. M., et al. (2016) · Gut · doi:10.1136/gutjnl-2015-309990 · Cited by 2,302 · see citing works
“The keystone-pathogen hypothesis 88 and the α -bug hypothesis both state that certain, low abundance microbiota members (such as enterotoxigenic B. fragilis ) possess unique virulence traits, which are pro-oncogenic and remodel the microbiome and in turn promote mucosal immune responses and colonic…”
Background
The Oral Microbiota: Dynamic Communities and Host Interactions
Lamont, R. J., Koo, H., & Hajishengallis, G. (2018) · Nature Reviews Microbiology · doi:10.1038/s41579-018-0089-x · Cited by 2,217 · see citing works
Self-citation
Role of the gut microbiota in immunity and inflammatory disease
Kamada, N., Seo, S.-U., Chen, G. Y., & Núñez, G. (2013) · Nature reviews. Immunology · doi:10.1038/nri3430 · Cited by 2,256 · see citing works
The microbiome and cancer
Schwabe, R. F., & Jobin, C. (2013) · Nature Reviews Cancer · doi:10.1038/nrc3610 · Cited by 1,689 · see citing works
Microbial Hub Taxa Link Host and Abiotic Factors to Plant Microbiome Variation
Agler, M. T., Ruhe, J., Kroll, S., Morhenn, C., Kim, S., Weigel, D., & Kemen, E. M. (2016) · PLoS Biology · doi:10.1371/journal.pbio.1002352 · Cited by 1,400 · see citing works
Beyond the red complex and into more complexity: the polymicrobial synergy and dysbiosis (PSD) model of periodontal disease etiology
Hajishengallis, G., & Lamont, R. J. (2012) · Molecular Oral Microbiology · doi:10.1111/j.2041-1014.2012.00663.x · Cited by 1,267 · see citing works
Self-citation
Immunomicrobial pathogenesis of periodontitis: keystones, pathobionts, and host response
Hajishengallis, G. (2014) · Trends in Immunology · doi:10.1016/j.it.2013.09.001 · Cited by 1,150 · see citing works
Self-citation
Porphyromonas gingivalis: An Overview of Periodontopathic Pathogen below the Gum Line
How, K. Y., Song, K. P., & Chan, K. G. (2016) · Frontiers in Microbiology · doi:10.3389/fmicb.2016.00053 · Cited by 858 · see citing works
Gut microbiota imbalance and colorectal cancer
Gagnière, J. (2016) · World Journal of Gastroenterology · doi:10.3748/wjg.v22.i2.501 · Cited by 856 · see citing works
Microbes, Microbiota, and Colon Cancer
Sears, C. L., & Garrett, W. S. (2014) · Cell Host & Microbe · doi:10.1016/j.chom.2014.02.007 · Cited by 820 · see citing works
Osteoimmunology: evolving concepts in bone–immune interactions in health and disease
Tsukasaki, M., & Takayanagi, H. (2019) · Nature reviews. Immunology · doi:10.1038/s41577-019-0178-8 · Cited by 789 · see citing works
Mechanisms of Bone Resorption in Periodontitis
Hienz, S. A., Paliwal, S., & Ivanovski, S. (2015) · Journal of Immunology Research · doi:10.1155/2015/615486 · Cited by 762 · see citing works
The oral microbiome: Role of key organisms and complex networks in oral health and disease
Sedghi, L., DiMassa, V., Harrington, A., Lynch, S. V., & Kapila, Y. L. (2021) · Periodontology 2000 · doi:10.1111/prd.12393 · Cited by 755 · see citing works
Prevotella Diversity, Niches and Interactions with the Human Host
Tett, A., Pasolli, E., Masetti, G., Ercolini, D., & Segata, N. (2021) · Nature Reviews Microbiology · doi:10.1038/s41579-021-00559-y · Cited by 748 · see citing works
The role of the microbiota in periodontal disease
Curtis, M. A., Diaz, P. I., & Van Dyke, T. E. (2020) · Periodontology 2000 · doi:10.1111/prd.12296 · Cited by 698 · see citing works
Self-citation
Molecular aspects of the pathogenesis of periodontitis
Meyle, J., & Chapple, I. (2015) · Periodontology 2000 · doi:10.1111/prd.12104 · Cited by 705 · see citing works
The cytokine network involved in the host immune response to periodontitis
Pan, W., Wang, Q., & Chen, Q. (2019) · International Journal of Oral Science · doi:10.1038/s41368-019-0064-z · Cited by 709 · see citing works
Gavage of Fecal Samples From Patients With Colorectal Cancer Promotes Intestinal Carcinogenesis in Germ-Free and Conventional Mice
Wong, S. H., Zhao, L., Zhang, X., Nakatsu, G., Han, J., Xu, W., Xiao, X., Kwong, T. N. Y., Tsoi, H., Wu, W. K. K., et al. (2017) · Gastroenterology · doi:10.1053/j.gastro.2017.08.022 · Cited by 634 · see citing works
Combined effects of host genetics and diet on human gut microbiota and incident disease in a single population cohort
Qin, Y., Havulinna, A. S., Liu, Y., Jousilahti, P., Ritchie, S. C., Tokolyi, A., Sanders, J. G., Valsta, L., Brożyńska, M., Zhu, Q., et al. (2022) · Nature Genetics · doi:10.1038/s41588-021-00991-z · Cited by 586 · see citing works
Neuroinflammation in Alzheimer disease
Heneka, M. T., van der Flier, W. M., Jessen, F., Hoozemanns, J., Thal, D. R., Boche, D., Brosseron, F., Teunissen, C., Zetterberg, H., Jacobs, A. H., et al. (2025) · Nature Reviews Immunology · doi:10.1038/s41577-024-01104-7 · Cited by 638 · see citing works
Polymicrobial synergy and dysbiosis in inflammatory disease
Lamont, R. J., & Hajishengallis, G. (2015) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2014.11.004 · Cited by 585 · see citing works
Self-citation
Optimization of the ligature-induced periodontitis model in mice
Abe, T., & Hajishengallis, G. (2013) · Journal of Immunological Methods · doi:10.1016/j.jim.2013.05.002 · Cited by 550 · see citing works
Self-citation
Polysaccharide Degradation by the Intestinal Microbiota and Its Influence on Human Health and Disease
Cockburn, D. W., & Koropatkin, N. M. (2016) · Journal of Molecular Biology · doi:10.1016/j.jmb.2016.06.021 · Cited by 542 · see citing works
Macrophage Polarization in Chronic Inflammatory Diseases: Killers or Builders?
Parisi, L., Gini, E., Baci, D., Tremolati, M., Fanuli, M., Bassani, B., Farronato, G., Bruno, A., & Mortara, L. (2018) · Journal of Immunology Research · doi:10.1155/2018/8917804 · Cited by 508 · see citing works
Current understanding of periodontal disease pathogenesis and targets for host‐modulation therapy
Hajishengallis, G., Chavakis, T., & Lambris, J. D. (2020) · Periodontology 2000 · doi:10.1111/prd.12331 · Cited by 513 · see citing works
Self-citation
Oral Mucosal Epithelial Cells
Groeger, S., & Meyle, J. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00208 · Cited by 473 · see citing works
The oralome and its dysbiosis: New insights into oral microbiome-host interactions
Radaic, A., & Kapila, Y. L. (2021) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2021.02.010 · Cited by 492 · see citing works
The Nexus Between Periodontal Inflammation and Dysbiosis
Dyke, T. E. V., Bartold, P. M., & Reynolds, E. C. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00511 · Cited by 465 · see citing works
Lung microbiome dynamics in COPD exacerbations
Wang, Z., Bafadhel, M., Haldar, K., Spivak, A., Mayhew, D. N., Miller, B. E., Tal‐Singer, R., Johnston, S. L., Ramsheh, M. Y., Barer, M. R., et al. (2016) · European Respiratory Journal · doi:10.1183/13993003.01406-2015 · Cited by 458 · see citing works
Present status and future directions: Microbiology of endodontic infections
Siqueira, J. F., Jr., & Rôças, I. N. (2021) · International Endodontic Journal · doi:10.1111/iej.13677 · Cited by 447 · see citing works
Porphyromonas gingivalis Manipulates Complement and TLR Signaling to Uncouple Bacterial Clearance from Inflammation and Promote Dysbiosis
Maekawa, T., Krauss, J. L., Abe, T., Jotwani, R., Triantafilou, M., Triantafilou, K., Hashim, A., Hoch, S., Curtis, M. A., Nussbaum, G., et al. (2014) · Cell Host & Microbe · doi:10.1016/j.chom.2014.05.012 · Cited by 430 · see citing works
Self-citation
Resilience of the Oral Microbiota in Health: Mechanisms That Prevent Dysbiosis
Rosier, B. T., Marsh, P. D., & Mira, A. (2018) · Journal of Dental Research · doi:10.1177/0022034517742139 · Cited by 448 · see citing works
The inflammophilic character of the periodontitis-associated microbiota
Hajishengallis, G. (2014) · Molecular Oral Microbiology · doi:10.1111/omi.12065 · Cited by 407 · see citing works
Self-citation
Precision Nutrition and the Microbiome, Part I: Current State of the Science
Mills, S., Stanton, C., Lane, J. A., Smith, G., & Ross, R. P. (2019) · Nutrients · doi:10.3390/nu11040923 · Cited by 406 · see citing works
Intestinal microbiota is altered in patients with colon cancer and modified by probiotic intervention
Hibberd, A. A., Lyra, A., Ouwehand, A. C., Rolny, P., Lindegren, H., Cedgård, L., & Wettergren, Y. (2017) · BMJ Open Gastroenterology · doi:10.1136/bmjgast-2017-000145 · Cited by 373 · see citing works
Roles of Porphyromonas gingivalis and its virulence factors in periodontitis
Xu, W., Zhou, W., Wang, H., & Liang, S. (2020) · Advances in protein chemistry and structural biology · doi:10.1016/bs.apcsb.2019.12.001 · Cited by 401 · see citing works
An experimental murine model to study periodontitis
Marchesan, J. T., Girnary, M., Li, J., Miao, M. Z., Zhang, S., Sun, L., Morelli, T., Schoenfisch, M. H., Inohara, N., Offenbacher, S., et al. (2018) · Nature Protocols · doi:10.1038/s41596-018-0035-4 · Cited by 389 · see citing works
Current concepts in the pathogenesis of periodontitis: from symbiosis to dysbiosis
Abdulkareem, A. A., Al-Taweel, F. B. H., Al-Sharqi, A. J. B., Gul, S. S., Sha, A. M., & Chapple, I. (2023) · Journal of Oral Microbiology · doi:10.1080/20002297.2023.2197779 · Cited by 402 · see citing works
Applying the core microbiome to understand host–microbe systems
Risely, A. (2020) · Journal of Animal Ecology · doi:10.1111/1365-2656.13229 · Cited by 370 · see citing works
Microbiome and colorectal cancer: Roles in carcinogenesis and clinical potential
Saus, E., Iraola‐Guzmán, S., Willis, J. R., Brunet‐Vega, A., & Gabaldón, T. (2019) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2019.05.001 · Cited by 348 · see citing works
A practical guide to the oral microbiome and its relation to health and disease
Krishnan, K., Chen, T., & Paster, B. (2017) · Oral Diseases · doi:10.1111/odi.12509 · Cited by 347 · see citing works
“The “keystone pathogen” hypothesis suggests that specific low-abundance pathogens can influence periodontal disease by altering the “healthy” microflora to a disease state (Hajishengallis et al., 2012).”
Background
Identifying Keystone Species in the Human Gut Microbiome from Metagenomic Timeseries Using Sparse Linear Regression
Fisher, C. K., & Mehta, P. (2014) · PLoS ONE · doi:10.1371/journal.pone.0102451 · Cited by 341 · see citing works
Functional signatures of oral dysbiosis during periodontitis progression revealed by microbial metatranscriptome analysis
Yost, S. C., Duran-Pinedo, A. E., Teles, R. P., Krishnan, K., & Frias‐Lopez, J. (2015) · Genome Medicine · doi:10.1186/s13073-015-0153-3 · Cited by 342 · see citing works
Oral Microbiome: A Review of Its Impact on Oral and Systemic Health
Krishnamurthy, H. K., Bosco, J., Jayaraman, V., Krishna, K., Wang, T., Bei, K., & Rajasekaran, J. J. (2024) · Microorganisms · doi:10.3390/microorganisms12091797 · Cited by 402 · see citing works
“Blooming” in the gut: how dysbiosis might contribute to pathogen evolution.
Stecher, B., Maier, L., & Hardt, W.-D. (2013) · Nature Reviews Microbiology · doi:10.1038/nrmicro2989 · Cited by 378 · see citing works
Breaking bad: Manipulation of the host response by Porphyromonas gingivalis
Hajishengallis, G., & Lamont, R. J. (2014) · European Journal of Immunology · doi:10.1002/eji.201344202 · Cited by 362 · see citing works
Self-citation
Mitigating amphibian chytridiomycosis with bioaugmentation: characteristics of effective probiotics and strategies for their selection and use
Bletz, M. C., Loudon, A. H., Becker, M. H., Bell, S. C., Woodhams, D. C., Minbiole, K. P. C., & Harris, R. N. (2013) · Ecology Letters · doi:10.1111/ele.12099 · Cited by 302 · see citing works
Defective Neutrophil Recruitment in Leukocyte Adhesion Deficiency Type I Disease Causes Local IL-17–Driven Inflammatory Bone Loss
Moutsopoulos, N. M., Konkel, J. E., Sarmadi, M., Eskan, M. A., Greenwell‐Wild, T., Dutzan, N., Abusleme, L., Zenobia, C., Hosur, K. B., Abe, T., et al. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3007696 · Cited by 303 · see citing works
Self-citation
Cancer-promoting effects of microbial dysbiosis
Sheflin, A. M., Whitney, A. K., & Weir, T. L. (2014) · Current Oncology Reports · doi:10.1007/s11912-014-0406-0 · Cited by 301 · see citing works
The Evolving Microbiome of Dental Caries
Spatafora, G., Li, Y., He, X., Cowan, A., & Tanner, A. C. R. (2024) · Microorganisms · doi:10.3390/microorganisms12010121 · Cited by 298 · see citing works
Polymicrobial communities in periodontal disease: Their quasi‐organismal nature and dialogue with the host
Hajishengallis, G., & Lamont, R. J. (2021) · Periodontology 2000 · doi:10.1111/prd.12371 · Cited by 302 · see citing works
Self-citation
Understanding and overcoming the pitfalls and biases of next-generation sequencing (NGS) methods for use in the routine clinical microbiological diagnostic laboratory
Boers, S. A., Jansen, R., & Hays, J. P. (2019) · European Journal of Clinical Microbiology & Infectious Diseases · doi:10.1007/s10096-019-03520-3 · Cited by 281 · see citing works
Role of microbial communities in the pathogenesis of periodontal diseases and caries
Mira, Á., Simón‐Soro, Á., & Curtis, M. A. (2017) · Journal Of Clinical Periodontology · doi:10.1111/jcpe.12671 · Cited by 283 · see citing works
Self-citation
The Role of Bacterial Biofilms in Dental Caries and Periodontal and Peri-implant Diseases: A Historical Perspective
Colombo, A. P. V., & Tanner, A. C. R. (2019) · Journal of Dental Research · doi:10.1177/0022034519830686 · Cited by 285 · see citing works
Dancing with the Stars: How Choreographed Bacterial Interactions Dictate Nososymbiocity and Give Rise to Keystone Pathogens, Accessory Pathogens, and Pathobionts
Hajishengallis, G., & Lamont, R. J. (2016) · Trends in Microbiology · doi:10.1016/j.tim.2016.02.010 · Cited by 275 · see citing works
“Accordingly, the keystonepathogen hypothesis holds that certain low-abundance microbes can promote the formation of and stabilize dysbiotic and disease-provoking communities [37] (Figure 1).”
BackgroundSelf-citation
Metagenomics for pathogen detection in public health
Miller, R. R., Montoya, V., Gardy, J. L., Patrick, D. M., & Tang, P. (2013) · Genome Medicine · doi:10.1186/gm485 · Cited by 266 · see citing works
Oral microbiota of periodontal health and disease and their changes after nonsurgical periodontal therapy
Chen, C., Hemme, C. L., Beleno, J., Shi, Z. J., Ning, D., Qin, Y., Tu, Q., Jorgensen, M. G., He, Z., Wu, L., et al. (2018) · The ISME Journal · doi:10.1038/s41396-017-0037-1 · Cited by 273 · see citing works
Gastrointestinal biofilms in health and disease
Motta, J., Wallace, J. L., Buret, A. G., Deraison, C., & Vergnolle, N. (2021) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-020-00397-y · Cited by 271 · see citing works
Voluntary and forced exercise differentially alters the gut microbiome in C57BL/6J mice
Allen, J. M., Berg Miller, M. E., Pence, B. D., Whitlock, K., Nehra, V., Gaskins, H. R., White, B. A., Fryer, J. D., & Woods, J. A. (2015) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01077.2014 · Cited by 266 · see citing works
The host-associated archaeome
Borrel, G., Brugère, J., Gribaldo, S., Schmitz, R. A., & Moissl‐Eichinger, C. (2020) · Nature Reviews Microbiology · doi:10.1038/s41579-020-0407-y · Cited by 255 · see citing works
Recurrent antibiotic exposure may promote cancer formation – Another step in understanding the role of the human microbiota?
Boursi, B., Mamtani, R., Haynes, K., & Yang, Y. (2015) · European Journal of Cancer · doi:10.1016/j.ejca.2015.08.015 · Cited by 263 · see citing works
Microbiome in Colorectal Cancer: How to Get from Meta-omics to Mechanism?
Ternes, D., Karta, J., Tsenkova, M., Wilmes, P., Haan, S., & Letellier, E. (2020) · Trends in Microbiology · doi:10.1016/j.tim.2020.01.001 · Cited by 256 · see citing works
IL-22 Deficiency Alters Colonic Microbiota To Be Transmissible and Colitogenic
Zenewicz, L. A., Yin, X., Wang, G., Elinav, E., Hao, L., Zhao, L., & Flavell, R. A. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1300016 · Cited by 251 · see citing works
The Noncanonical Pathway for In Vivo Nitric Oxide Generation: The Nitrate-Nitrite-Nitric Oxide Pathway
Kapil, V., Khambata, R. S., Jones, D. A., Rathod, K., Primus, C., Massimo, G., Fukuto, J. M., & Ahluwalia, A. (2020) · Pharmacological Reviews · doi:10.1124/pr.120.019240 · Cited by 248 · see citing works
Systemic antibiotics in the treatment of periodontitis
Feres, M., Figueiredo, L. C., Soares, G. M. S., & Faveri, M. (2014) · Periodontology 2000 · doi:10.1111/prd.12075 · Cited by 245 · see citing works
Changes in cystic fibrosis airway microbiota at pulmonary exacerbation
Carmody, L. A., Zhao, J., Schloss, P. D., Petrosino, J. F., Murray, S., Young, V. B., Li, J. Z., & LiPuma, J. J. (2013) · Annals of the American Thoracic Society · doi:10.1513/annalsats.201211-107oc · Cited by 239 · see citing works
First Insights into the Diverse Human Archaeome: Specific Detection of Archaea in the Gastrointestinal Tract, Lung, and Nose and on Skin
Koskinen, K., Pausan, M.-R., Perras, A., Beck, M., Bang, C., Mora, M., Schilhabel, A., Schmitz, R. A., & Moissl‐Eichinger, C. (2017) · mBio · doi:10.1128/mbio.00824-17 · Cited by 231 · see citing works
Colonization with enterotoxigenic Bacteroides fragilis is associated with early-stage colorectal neoplasia
Purcell, R. V., Pearson, J., Aitchison, A., Dixon, L., Frizelle, F. A., & Keenan, J. I. (2017) · PLoS ONE · doi:10.1371/journal.pone.0171602 · Cited by 230 · see citing works
Epithelial barrier and oral bacterial infection
Groeger, S. E., & Meyle, J. (2015) · Periodontology 2000 · doi:10.1111/prd.12094 · Cited by 229 · see citing works
The intestinal microbiome, barrier function, and immune system in inflammatory bowel disease: a tripartite pathophysiological circuit with implications for new therapeutic directions
Vindigni, S. M., Zisman, T. L., Suskind, D. L., & Damman, C. J. (2016) · Therapeutic Advances in Gastroenterology · doi:10.1177/1756283x16644242 · Cited by 228 · see citing works
Oral Microbes, Biofilms and Their Role in Periodontal and Peri-Implant Diseases
Lasserre, J. F., Brecx, M., & Toma, S. (2018) · Materials · doi:10.3390/ma11101802 · Cited by 229 · see citing works
Host modulation: controlling the inflammation to control the infection
Bartold, P. M., & Dyke, T. E. V. (2017) · Periodontology 2000 · doi:10.1111/prd.12169 · Cited by 231 · see citing works
Modifiable risk factors in periodontitis: at the intersection of aging and disease
Reynolds, M. A. (2013) · Periodontology 2000 · doi:10.1111/prd.12047 · Cited by 225 · see citing works
Plant-Derived Exosomal Nanoparticles Inhibit Pathogenicity of Porphyromonas gingivalis
Sundaram, K., Miller, D. P., Kumar, A., Teng, Y., Sayed, M. E., Mu, J., Lei, C., Sriwastva, M. K., Zhang, L., Yan, J., et al. (2019) · iScience · doi:10.1016/j.isci.2019.10.032 · Cited by 226 · see citing works
Mechanism of alveolar bone destruction in periodontitis — Periodontal bacteria and inflammation
Usui, M., Onizuka, S., Sato, T., Kokabu, S., Ariyoshi, W., & Nakashima, K. (2021) · Japanese Dental Science Review · doi:10.1016/j.jdsr.2021.09.005 · Cited by 239 · see citing works
The Role of Curcumin in Modulating Colonic Microbiota During Colitis and Colon Cancer Prevention
McFadden, R.-M. T., Larmonier, C. B., Shehab, K. W., Midura‐Kiela, M. T., Ramalingam, R., Harrison, C. A., Besselsen, D. G., Chase, J., Caporaso, J. G., Jobin, C., et al. (2015) · Inflammatory Bowel Diseases · doi:10.1097/mib.0000000000000522 · Cited by 228 · see citing works
Critical role of environmental factors in the pathogenesis of psoriasis
Zeng, J., Luo, S., Huang, Y., & Lu, Q. (2017) · The Journal of Dermatology · doi:10.1111/1346-8138.13806 · Cited by 229 · see citing works
Effects of Bifidobacterium probiotic on the treatment of chronic periodontitis: A randomized clinical trial
Invernici, M. D. M., Salvador, S. L. D. S., Silva, P. H. F., Soares, M. S. M., Casarin, R. C. V., Palioto, D. B., de Souza, S. L. S., Taba, M., Novaes, A. B., Furlaneto, F. A. C., et al. (2018) · Journal Of Clinical Periodontology · doi:10.1111/jcpe.12995 · Cited by 218 · see citing works
The potential role of lung microbiota in lung cancer attributed to household coal burning exposures
Hosgood, H. D., Sapkota, A. R., Rothman, N., Rohan, T. E., Hu, W., Xu, J., Vermeulen, R. C. H., He, X., White, J. R., Wu, G., et al. (2014) · Environmental and Molecular Mutagenesis · doi:10.1002/em.21878 · Cited by 214 · see citing works
The periodontal war: microbes and immunity
Ebersole, J. L., Dawson, D. R., Emecen‐Huja, P., Nagarajan, R., Howard, K., Grady, M. E., Thompson, K. L., Peyyala, R., Al‐Attar, A., Lethbridge, K., et al. (2017) · Periodontology 2000 · doi:10.1111/prd.12222 · Cited by 211 · see citing works
Metabolic Remodeling, Inflammasome Activation, and Pyroptosis in Macrophages Stimulated by Porphyromonas gingivalis and Its Outer Membrane Vesicles
Fleetwood, A. J., Lee, M. K. S., Singleton, W., Achuthan, A. A., Lee, M.-C., O’brien-simpson, N. M., Cook, A. D., Murphy, A. J., Dashper, S. G., Reynolds, E. C., et al. (2017) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2017.00351 · Cited by 206 · see citing works
Possible role of Porphyromonas gingivalis in orodigestive cancers
Olsen, I., & Yilmaz, Ö. (2019) · Journal of Oral Microbiology · doi:10.1080/20002297.2018.1563410 · Cited by 207 · see citing works
Resilience of the oral microbiome
Wade, W. G. (2021) · Periodontology 2000 · doi:10.1111/prd.12365 · Cited by 205 · see citing works
Microbial Community Shifts Associated With the Ongoing Stony Coral Tissue Loss Disease Outbreak on the Florida Reef Tract
Meyer, J. L., Castellanos-Gell, J., Aeby, G. S., Häse, C. C., Ushijima, B., & Paul, V. J. (2019) · Frontiers in Microbiology · doi:10.3389/fmicb.2019.02244 · Cited by 201 · see citing works
Porphyromonas gingivalis Periodontal Infection and Its Putative Links with Alzheimer’s Disease
Singhrao, S. K., Harding, A., Poole, S., Kesavalu, L., & Crean, S. (2015) · Mediators of Inflammation · doi:10.1155/2015/137357 · Cited by 195 · see citing works
Gut microbiota and colorectal cancer
Gao, R., Gao, Z., Huang, L., & Qin, H. (2017) · European Journal of Clinical Microbiology & Infectious Diseases · doi:10.1007/s10096-016-2881-8 · Cited by 205 · see citing works
Historical and contemporary hypotheses on the development of oral diseases: are we there yet?
Rosier, B. T., de Jager, M., Zaura, E., & Krom, B. P. (2014) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2014.00092 · Cited by 199 · see citing works
Can an Infection Hypothesis Explain the Beta Amyloid Hypothesis of Alzheimer’s Disease?
Fülöp, T., Witkowski, J. M., Bourgade, K., Khalil, A., Zerif, E., Larbi, A., Hirokawa, K., Pawelec, G., Bocti, C., Lacombe, G., et al. (2018) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2018.00224 · Cited by 201 · see citing works
Microbial community assembly in wild populations of the fruit fly Drosophila melanogaster
Adair, K. L., Wilson, M., Bost, A., & Douglas, A. E. (2018) · The ISME Journal · doi:10.1038/s41396-017-0020-x · Cited by 198 · see citing works
New developments in neutrophil biology and periodontitis
Hajishengallis, G. (2019) · Periodontology 2000 · doi:10.1111/prd.12313 · Cited by 198 · see citing works
Self-citation
Periodontal disease, edentulism, and pancreatic cancer: a meta-analysis
Maisonneuve, P., Amar, S., & Lowenfels, A. B. (2017) · Annals of Oncology · doi:10.1093/annonc/mdx019 · Cited by 197 · see citing works
The role of oral bacteria in inflammatory bowel disease
Read, E., Curtis, M. A., & Neves, J. F. (2021) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-021-00488-4 · Cited by 198 · see citing works
Self-citation
Periodontal Pathogens as Risk Factors of Cardiovascular Diseases, Diabetes, Rheumatoid Arthritis, Cancer, and Chronic Obstructive Pulmonary Disease—Is There Cause for Consideration?
Bourgeois, D. M., Inquimbert, C., Ottolenghi, L., & Carrouel, F. (2019) · Microorganisms · doi:10.3390/microorganisms7100424 · Cited by 190 · see citing works
Dysbiosis in intestinal inflammation: Cause or consequence
Buttó, L. F., & Haller, D. (2016) · International Journal of Medical Microbiology · doi:10.1016/j.ijmm.2016.02.010 · Cited by 189 · see citing works
The germ-organ theory of non-communicable diseases
Byndloss, M. X., & Bäumler, A. J. (2018) · Nature Reviews Microbiology · doi:10.1038/nrmicro.2017.158 · Cited by 185 · see citing works
‘NetShift’: a methodology for understanding ‘driver microbes’ from healthy and disease microbiome datasets
Kuntal, B. K., Chandrakar, P., Sadhu, S., & Mande, S. S. (2018) · The ISME Journal · doi:10.1038/s41396-018-0291-x · Cited by 177 · see citing works
An appraisal of the role of specific bacteria in the initial pathogenesis of periodontitis
Bartold, P. M., & Van Dyke, T. E. (2019) · Journal of Clinical Periodontology · doi:10.1111/jcpe.13046 · Cited by 181 · see citing works
Porphyromonas gingivalis disturbs host–commensal homeostasis by changing complement function
Olsen, I., Lambris, J. D., & Hajishengallis, G. (2017) · Journal of Oral Microbiology · doi:10.1080/20002297.2017.1340085 · Cited by 175 · see citing works
Self-citation

Inflammatory disease caused by intestinal pathobionts
Zechner, E. L. (2017) · Current Opinion in Microbiology · doi:10.1016/j.mib.2017.01.011 · Cited by 76 · see citing works
Dancing with the Stars: How Choreographed Bacterial Interactions Dictate Nososymbiocity and Give Rise to Keystone Pathogens, Accessory Pathogens, and Pathobionts
Hajishengallis, G., & Lamont, R. J. (2016) · Trends in Microbiology · doi:10.1016/j.tim.2016.02.010 · Cited by 275 · see citing works
Self-citation
Polymicrobial synergy and dysbiosis in inflammatory disease
Lamont, R. J., & Hajishengallis, G. (2015) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2014.11.004 · Cited by 585 · see citing works
Self-citation
Next Generation Microbiome Research: Identification of Keystone Species in the Metabolic Regulation of Host-Gut Microbiota Interplay
Tudela, H., Claus, S. P., & Saleh, M. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.719072 · Cited by 79 · see citing works
Defining dysbiosis and its influence on host immunity and disease
Petersen, C., & Round, J. L. (2014) · Cellular Microbiology · doi:10.1111/cmi.12308 · Cited by 1,185 · see citing works

Authors: Hajishengallis, G., Darveau, R. P., & Curtis, M. A.
Affiliations: University of Pennsylvania (US)
University of Washington (US)
Queen Mary University of London (GB)
Corresponding author: Hajishengallis, George
ORCID: Hajishengallis, George
Darveau, Richard P.
Curtis, Michael A.
Venue: Nature Reviews Microbiology
Publisher: Springer Science and Business Media LLC
Published: 2012-09-03
Volume: 10
Issue: 10
Pages: 717-725
ISSN: 1740-1526 (ISSN-L)
1740-1534
DOI: 10.1038/nrmicro2873
PMC: PMC3498498
OpenAlex: W2043248182
Cited by: 1,790
References: 86
Citations by year: 2026: 163 · 2025: 149 · 2024: 146 · 2023: 172 · 2022: 146 · 2021: 199 · 2020: 167 · 2019: 125 · 2018: 116 · 2017: 101 · 2016: 100 · 2015: 77 · 2014: 63 · 2013: 58 · 2012: 4
FWCI: 5.89
Type: journal article
Language: en
Open access: green
europepmc.org
Licence: www.springer.com/tdm (tdm)
Locations: Nature Reviews Microbiology (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health
Medical Research Council (MR/J011118/1)
National Institute of Dental and Craniofacial Research (R01DE018292, DE-015254, R01DE015254, DE012768, DE021580, DE18274, DE021685, R01DE018274, DE018292, RC4DE021580, R01DE021685, R01DE012768)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacterial biofilms and quorum sensing
Keywords: human microbiome, dysbiosis, commensal microbiota, inflammatory diseases, targeted therapeutics
MeSH terms: Bacteria, Colonic Neoplasms, Humans, Inflammation, Models, Biological, Periodontitis, Inflammatory Bowel Diseases, Host-Pathogen Interactions, Metagenome, Microbial Interactions

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

The keystone-pathogen hypothesis

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Self-check

Cites

Cited by

Related

Record

About these checks