Philip Ahern Laboratory

Research

Overview

Research in our group focuses on understanding how homeostasis between the intestinal immune system and the gut microbiota is established and maintained, and how disruption of this relationship leads to the development and exacerbation of inflammatory bowel disease (IBD).

Our gut microbiota, the vast collection of harmless and beneficial microbes and viruses that inhabit our intestines, are key contributors to host health. IBD, encompassing Crohn's Disease (CD) and Ulcerative Colitis (UC), represent a set of severe inflammatory disorders of the gastrointestinal tract that result from inflammatory immune responses directed against members of the gut microbiota. A variety of immune cell types, from both the innate and adaptive immune compartments, have been implicated in the pathogenesis of IBD. Our work is aimed at further increasing our understanding of the dynamic interplay between intestinal CD4+ T cells and the gut microbiota during the development of intestinal inflammation, and how the gut microbiota can be targeted to treat IBD and restore host health.

Our group is currently focused on a number of questions related to the development and pathogenesis of IBD:

(1) What are the specific members of the microbiota that are responsible for the initiation and perpetuation of chronic inflammation in the intestine?

(2) How do gut microbes survive inflammatory environments to stably colonize the host?

(3) How do members of the gut microbiota regulate intestinal CD4+ T cell fate during steady state and disease?

(4) What pathways promote the resolution of bacterially-triggered intestinal inflammation and restoration of immune-microbiota homeostasis?

(5) How can the microbiota be modified to promote effective mucosal vaccination strategies?

To address these questions our group employs a variety of cellular and molecular approaches allied to murine models of IBD in gnotobiotic and specific pathogen-free mice.

Our overarching goal is to identify host and microbial pathways that can be targeted to facilitate the development of new and improved therapeutic strategies for the treatment of IBD.

Selected Publications

View publications for Philip Ahern, DPhil
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Peer Reviewed/Pre-prints:

Engelhart MJ, Glowacki RWP, Harding CV, Martens EC, Ahern PP.
The NQR pathway regulates the immunomodulatory function of Bacteroides thetaiotaomicron.
bioRxiv, Preprint, available from doi: https://doi.org/10.1101/2022.10.21.513251 (posted 2022, October 22)  

Chambers L, Esakov EL, Braley C, Trestan L, Alali Z, Bayik D, Lathia J, Sangwan N, Bazeley P, Joehlin-Price AS, Dwidar M, Hajjar A, Ahern PP, Claesen J, Rose P, Vargas R, Michener C, Reizes O.
Disruption of the gut microbiota attenuates epithelial ovarian cancer sensitivity to cisplatin therapy.
Cancer Research, 2022 Dec 16;82(24):4654-4669. 

Osborn LJ, Schultz K, Massey WJ, DeLucia B, Choucair I, Varadharajan V, Banerjee R, Fung K, Horak AJ, Orabi DJ, Nemet I, Nagy LE, Wang Z, Allende DS, Willard BB, Sangwan N, Hajjar AM, McDonald C, Ahern PP, Hazen SL, Brown JM, Claesen J.
A gut microbial metabolite of dietary polyphenols reverses obesity-driven hepatic steatosis.
Proc. Natl. Acad. Sci., 2022 Nov 29;119(48):e2202934119. doi: 10.1073/pnas.2202934119      

Zangara MT, Ponti AK, Miller ND, Engelhart MJ, Ahern PP, Sangwan N, McDonald C.
Maltodextrin Consumption Impairs the Intestinal Mucus Barrier and Accelerates Colitis Through Direct Actions on the Epithelium.
Frontiers in Immunology, 2022 Mar 14;13:841188.

Johnston I, Osborn LJ, McManus EA, Kadam A, Schultz KB, Ahern PP, Brown JM, Claesen J.
Identification of essential genes for Escherichia coli aryl polyene biosynthesis and function in biofilm formation.
NPJ Biofilms Microbiomes, 2021 Jul 2;7(1):56.     

Wu M, Chen Y, Xia H, Wang C, Tan CY, Cai X, Liu Y, Ji F, Xiong P, Liu R, Guan Y, Duan Y, Kuang D, Xu S, Cai H, Xia Q, Yang D, Wang MW, Chiu IM, Cheng C, Ahern PP, Liu L, Wang G, Surana NK, Xia T, Kasper DL.
Transcriptional and proteomic insights into the host response in fatal COVID-19 cases.
Proc. Natl. Acad. Sci., 2020 Oct 20:202018030

Di Luccia B*, Ahern PP*, Griffin NW*, Cheng J, Guruge JL, Byrne AE, Rodionov DA, Leyn SA, Osterman  AL, Ahmed T, Colonna M, Barratt MJ, Delahaye NF, Gordon JI.
Combined Prebiotic and Microbial Intervention Improves Oral Cholera Vaccination Responses in a Mouse Model of Childhood Undernutrition. Cell Host Microbe, 2020 Jun 10;27(6):899-908.e5
*, equal contribution

Cowardin CA, Ahern PP, Kung VL, Hibberd MC, Cheng J, Guruge JL, Sundaresan V, Head RD, Barile D, Mills DA, Barratt MJ, Huq S, Ahmed T, Gordon JI.
Mechanisms by which sialylated milk oligosaccharides impact bone biology in a gnotobiotic mouse model of infant undernutrition.
Proc. Natl. Acad. Sci., 2019 Jun 11;116(24):11988-11996

Cervantes-Barragan L, Chai JN, Tianero MD, Di Luccia B, Ahern PP, Merriman J, Cortez VS, Caparon MG, Donia MS, Gilfillan S, Cella M, Gordon JI, Hsieh CS, Colonna M.
Lactobacillus reuteri induces gut intraepithelial CD4+CD8αα+ T cells.
Science, 2017 Aug 25; 357(6353): 806-810

Griffin NW, Ahern PP, Cheng J, Heath AC, Ilkayeva O, Newgard CB, Fontana L, Gordon JI.
Prior Dietary Practices and Connections to a Human Gut Microbial Metacommunity Alter Responses to Diet Interventions.
Cell Host Microbe., 2017 Jan 11;21(1):84-96

Semenkovich NP, Planer JD, Ahern PP, Griffin NW, Lin CY, Gordon JI.
Impact of the gut microbiota on enhancer accessibility in gut intraepithelial lymphocytes.
Proc. Natl. Acad. Sci., 2016 Dec 20;113(51):14805-14810.

Wagner VE, Dey N, Guruge J, Hsiao A, Ahern PP, Semenkovich NP, Blanton LV, Cheng J, Griffin N, Stappenbeck TS, Ilkayeva O, Newgard CB, Petri W, Haque R, Ahmed T, Gordon JI.
Effects of a gut pathobiont in a gnotobiotic mouse model of childhood undernutrition.
Sci. Transl. Med., 2016 Nov 23;8(366):366ra164.

Krausgruber T, Schiering C, Adelmann K, Harrison OJ, Chomka A, Pearson C, Ahern PP, Shale M, Oukka M, Powrie F.
T-bet is a key modulator of IL-23-driven pathogenic CD4(+) T cell responses in the intestine.
Nat. Commun., 2016 May 19;7:11627

Rakoff-Nahoum S, Kong Y, Kleinstein SH, Subramanian S, Ahern PP, Gordon JI, Medzhitov R.
Analysis of gene-environment interactions in postnatal development of the mammalian intestine.
Proc. Natl. Acad. Sci., 2015 Feb 17;112(7):1929-36

Faith JJ*, Ahern PP*, Ridaura VK, Cheng J, Gordon JI.
Identifying gut microbe-host phenotype relationships using combinatorial communities in gnotobiotic mice.
Sci Transl Med., 2014 Jan 22;6(220):220ra11
*, equal contribution

Rey FE, Gonzalez MD, Cheng J, Wu M, Ahern PP, Gordon JI.
Metabolic niche of a prominent sulfate-reducing human gut bacterium.
Proc. Natl. Acad. Sci., 2013 Aug 13; 110(33):13582-7

Yockey LJ, Demehri S, Turkoz M, Turkoz A, Ahern PP, Jassim O, Manivasagam, Kearney JF, Gordon JI, Kopan R.
The absence of a microbiota enhances TSLP expression in mice with defective skin barrier but does not affect the severity of their allergic inflammation.
J Invest Dermatol., 2013 Epub May 22; 133(12):2714-21

Ahern PP*, Schiering C*, Buonocore S, McGeachy MJ, Cua DJ, Maloy KJ, Powrie F.
Interleukin-23 drives intestinal inflammation through direct activity on T cells.
Immunity, 2010 Aug 27;33(2):279-88
*, equal contribution

Buonocore S, Ahern PP, Uhlig HH, Ivanov II, Littman DR, Maloy KJ and Powrie F.
Innate lymphoid cells drive interleukin-23 dependent innate intestinal pathology.
Nature, 2010 Apr 29;464(7293):1371-5

Izcue A, Hue S, Buonocore S, Arancibia-Cárcamo CV, Ahern PP, Iwakura Y, Maloy KJ and Powrie F.
Interleukin-23 restrains regulatory T cell activity to drive T cell-dependent colitis.
Immunity, 2008 Apr;28(4):559-70

Hue S, Ahern P, Buonocore S, Kullberg MC, Cua DJ, McKenzie BS, Powrie F and Maloy KJ.
Interleukin-23 drives innate and T cell-mediated intestinal inflammation.
J Exp Med., 2006 Oct 30;203(11):2473-83

Reviews:

Glowacki RWP, Engelhart MJ, Ahern PP.
Controlled Complexity: Optimized systems to study the role of the gut microbiome in host physiology Frontiers in Microbiology, 2021 Sep 27;12:735562. 

Ahern PP, Maloy KJ.
Understanding immune-microbiota interactions in the intestine.
Immunology. 2020 Jan;159(1):4-14.

Ahmed T, Auble D, Berkley JA, Black R, Ahern PP, Hossain M, Hsieh A, Ireen S, Arabi M, Gordon JI.
An evolving perspective about the origins of childhood undernutrition and nutritional interventions that includes the gut microbiome.
Ann N Y Acad Sci., 2014 Aug 12, doi: 10.1111/nyas.12487

Ahern PP*, Faith JJ*, Gordon JI.
Mining the human gut microbiota for effector strains that shape the immune system.
Immunity, 2014 Jun 19;40(6):815-23
*, equal contribution

Kau AL*, Ahern PP*, Griffin NW, Goodman AL, Gordon JI.
Human nutrition, the gut microbiome and the immune system.
Nature, 2011 Jun 15; 474(7351):327-36
*, equal contribution

Ahern PP, Izcue A, Maloy KJ and Powrie F.
The interleukin-23 axis in Intestinal Inflammation.
Immunological Reviews, 2008, Dec;226;147-59