Preprints (hidden for now)

Inhibition of microbial deconjugation of micellar bile acids protects against intestinal permeability and liver injury
Li DK, Chaudhari SN, Sojoodi M, Lee Y, Adhikari AA, Zhuo Z, Zukerberg L, Shroff S, Barrett SC, Boursier J, Diehl AM, Sui SH, Tanabe K, Chung RT, Devlin AS.
bioRxiv 2021 bioRxiv
Gut microbiota depletion exacerbates cholestatic liver injury via loss of FXR signalling
Schneider KM, Candels LS, Hov JR, Myllys M, Hassan R, Schneider CV, Wahlström A, Mohs A, Zühlke S, Liao L, Elfers C, Kilic K, Henricsson M, Molinaro A, Hatting M, Zaza A, Drasdo D, Frissen M, Devlin AS, Gálvez EJC, Strowig T, Karlsen TH, Hengstler JG, Marschall HU, Ghallab A, Trautwein C.
Nature Metabolism 2021, 3 (9), 1228–1241. DOI


Host–microbiome orchestration of the sulfated metabolome
D’Agostino GD, Chaudhari SN, Devlin AS.
Nature Chemical Biology 2024. DOI
Inhibition of microbial deconjugation of micellar bile acids protects against intestinal permeability and liver injury
Li DK, Chaudhari SN, Sojoodi M, Lee Y, Adhikari AA, Zhuo Z, Zukerberg L, Shroff S, Barrett SC, Boursier J, Diehl AM, Sui SH, Tanabe K, Chung RT, Devlin AS.
Science Advances 2022, 8 (34). DOIbioRxiv
Press Coverage: HMS instagram post
A biosynthetic pathway for the selective sulfonation of steroidal metabolites by human gut bacteria
Yao L, D’Agostino GD, Park J, Hang S, Adhikari AA, Zhang Y, Li W, Avila-Pacheco J, Bae S, Clish CB, Franzosa EA, Huttenhower C, Huh JR, Devlin AS.
Nature Microbiology 2022, 7 (9), 1404–1418. DOI
Press Coverage: Nature Microbiology News & Views
Human gut bacteria produce TH17-modulating bile acid metabolites
Paik D,  Yao L, Zhang Y, Bae S, D’Agostino GD, Kim E, Franzosa EA, Avila-Pacheco J, Bisanz JE, Rakowski CK, Vlamakis H, Xavier RJ, Turnbaugh PJ, Longman RS, Krout MK, Clish CB, Huttenhower C, Huh JR, Devlin AS.
Nature 2022603 (7903), 907–912. DOI, bioRxiv
Press Coverage: HMS News and ResearchNature Methods  
Lessons learned by an organic chemist entering the microbiome field
Devlin AS.
Cell Host & Microbe 202230 (4), 435–438. DOI
Chains of evidence from correlations to causal molecules in microbiome-linked diseases
Chaudhari SN, McCurry MD, Devlin AS.
Nature Chemical Biology 202117 (10), 1046–1056. DOI
Press Coverage: Featured on the cover of Nature Chemical Biology (photo on the right)
A bacterial bile acid metabolite modulates Treg activity through the nuclear hormone receptor NR4A1
Li W, Hang S, Fang Y, Bae S, Zhang Y, Wang G, McCurry MD, Bae M, Frazosa EA, Huttenhower C, Yao L, Devlin AS, Huh JR.
Cell Host & Microbe 202129 (9), 1366–1377.e9. DOI, bioRxiv
A gut-restricted lithocholic acid analog as an inhibitor of gut bacterial bile salt hydrolases
Adhikari AA, Ramachandran D, Chaudhari SN, Powell CE, McCurry MD, Banks AS, Devlin AS.
ACS Chemical Biology 202116 (8), 1401–1412. DOI, bioRxiv
Intestinal co-culture system to study TGR5 agonism and gut restriction
Chaudhari SN, Devlin AS.
Bio-protocol 202111 (6), e3948. DOI
A microbial metabolite remodels the gut-liver axis following bariatric surgery
Chaudhari SN, Luo JN, Harris DA, Aliakbarian H, Yao L, Paik D, Subramaniam R, Adhikari AA, Vernon AH, Kilic A, Weiss ST, Huh JR, Sheu EG, Devlin AS.
Cell Host & Microbe 202129 (3), 408–424.e7. DOI
Bariatric surgery reveals a gut-restricted TGR5 agonist with anti-diabetic effects
Chaudhari SN, Harris DA, Aliakbarian H, Luo JN, Henke MT, Subramaniam R, Vernon AH, Tavakkoli A, Sheu EG, Devlin AS.
Nature Chemical Biology 2021, 17 (1), 20–29. DOI, bioRxiv
Press Coverage: C&E NewsNature Chemical Biology News & ViewsHMS News and ResearchTranslational Chemical Biology conference press highlightCell Host & Microbe preview
Development of a covalent inhibitor of gut bacterial bile salt hydrolases
Adhikari AA, Seegar TCM, Ficarro SB, McCurry MD, Ramachandran D, Yao L, Chaudhari SN, Ndousse-Fetter S, Banks AS, Marto JA, Blacklow SC, Devlin AS.
Nature Chemical Biology 202016 (3), 318–326. DOI, bioRxiv
Press Coverage: Featured on the cover of Nature Chemical Biology (photo on the right)
Bile acid metabolites control TH17 and Treg cell differentiation
Hang S, Paik D, Yao L, Kim E, Jamma T, Lu J, Ha S, Nelson BN, Kelly SP, Wu L, Zheng Y, Longman RS, Rastinejad F, Devlin AS, Krout MR, Fischbach MA, Littman DR, Huh JR.
Nature 2019576 (7785), 143–148. DOI, bioRxiv
A selective gut bacterial bile salt hydrolase alters host metabolism
Yao L, Seaton SC, Ndousse-Fetter S, Adhikari AA, DiBenedetto N, Mina AI, Banks AS, Bry L, Devlin AS.
eLife 2018, 7, e37182. DOI
Press Coverage: HMS News and ResearchScience Daily
Modulation of a circulating uremic solute via rational genetic manipulation of the gut microbiota
Devlin AS, Marcobal A, Dodd D, Nayfach S, Plummer N, Meyer T, Pollard KS, Sonnenburg JL, Fischbach MA.
Cell Host & Microbe 201620 (6), 709–715. DOI
Inhibition of sodium ion channel function with truncated forms of batrachotoxin
Toma T, Logan MM, Menard F, Devlin AS, Du Bois J.
ACS Chemical Neuroscience 20167 (10), 1463–1468. DOI
A biosynthetic pathway for a prominent class of microbiota-derived bile acids
Devlin AS, Fischbach MA.
Nature Chemical Biology 201511 (9), 685–690. DOI
Diet rapidly and reproducibly alters the human gut microbiome
David LA, Maurice CM, Carmody RN, Gootenberg DB, Button JE, Wolfe BE, Ling AV, Devlin AS, Varma Y, Fischbach MA, Biddinger SB, Dutton RJ, Turnbaugh PJ.
Nature 2014505 (7484), 559–563. DOI
Modular synthesis of the pentacyclic core of batrachotoxin and select batrachotoxin analogue designs
Devlin AS, Du Bois J.
Chemical Science 2013, 4 (3), 1059–1063. DOI
δ-Sultone formation through Rh-catalyzed C–H Insertion
Wolckenhauer SA, Devlin AS, Du Bois J.
Organic Letters 20079 (21), 4363–4366. DOI


Batrachotoxin analogues, compositions, uses, and preparation thereof
US Patent No. 9,090,627. link
Compositions and methods related to cholic acid-7-sulfate as a treatment for diabetes
WO/2020/041673 link
Small molecule modulators of gut bacterial bile acid metabolism
WO/2020/231776 link
Synthetic derivatives of cholic acid-7-sulfate and uses thereof
WO/2020/117945 link
Sulfated compounds have canonically been classified as waste products; however, studies have revealed a variety of physiological roles for these metabolites, including effects on host metabolism, immune response and neurological function. Moreover, recent research has revealed that commensal bacteria either chemically modify or synthesize a variety of sulfated compounds. In a 2024 Nature Chemical Biology review article, we explore how host–microbiome collaborative metabolism transforms the sulfated metabolome.
Unconjugated bile acids resulting from microbial deconjugation induce leaky gut by disturbing gut epithelial tight junctions. Conjugated bile acids protect against this injury by sequestering toxic unconjugated bile acids in micelles (shown above), thus preventing their disruptive action on the gut epithelium. Image captured by electron microscopy with negative staining at the Harvard Medical School EM core.
Representative TEM images of Caco-2 cells from transwells after exposure to unconjugated bile acid pools at 2 mM. The white arrow points to tight junction dilatation. Scale bar=500 nm.
The human gut bacterium Clostridium scindens produces the secondary bile acids deoxycholic acid and lithocholic acid, which have protective effects in diabetes and other diseases. The image shows C. scindens (in pink) on a human intestinal epithelial cell, demonstrating the close physical relationships between microbiome and host cells.
Magnified under a microscope, differentiated human intestinal cells in a dish show tight junctions between cells and waves of tentacle-like microvilli on cell surfaces.
The bacteria of the human microbiota use bile salt hydrolases (BSHs) to generate dozens of secondary bile acids that can bind to host receptors, including nuclear receptors and G-protein-coupled receptors. A covalent inhibitor generated by appending an electrophile to the sterol core of a bile acid can inhibit all of the BSH activity in rodent microbiota and could prove useful for understanding the effects of bile acids on host physiology.
Mice colonized with an altered gut bacterium had less fat accumulation in the liver (right) than mice with a normal gut bacterium (left).