A widely distributed gene cluster compensates for uricase loss in hominids

Yuanyuan Liu; J. Bryce Jarman; Yen S. Low; Hannah E. Augustijn; Steven Huang; Haoqing Chen; Mary E. DeFeo; Kazuma Sekiba; Bi Huei Hou; Xiandong Meng; Allison M. Weakley; Ashley V. Cabrera; Zhiwei Zhou; Gilles van Wezel; Marnix H. Medema; Calyani Ganesan; Alan C. Pao; Saurabh Gombar; Dylan Dodd

doi:10.1016/j.cell.2023.06.010

A widely distributed gene cluster compensates for uricase loss in hominids

Yuanyuan Liu, J. Bryce Jarman, Yen S. Low, Hannah E. Augustijn, Steven Huang, Haoqing Chen, Mary E. DeFeo, Kazuma Sekiba, Bi Huei Hou, Xiandong Meng, Allison M. Weakley, Ashley V. Cabrera, Zhiwei Zhou, Gilles van Wezel, Marnix H. Medema, Calyani Ganesan, Alan C. Pao, Saurabh Gombar, Dylan Dodd^* (Co-auteur)

^*Bijbehorende auteur voor dit werk

NIOO - Microbial Ecology (ME)

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgave › Artikel › Wetenschappelijk › peer review

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Approximately 15% of US adults have circulating levels of uric acid above its solubility limit, which is causally linked to the disease gout. In most mammals, uric acid elimination is facilitated by the enzyme uricase. However, human uricase is a pseudogene, having been inactivated early in hominid evolution. Though it has long been known that uric acid is eliminated in the gut, the role of the gut microbiota in hyperuricemia has not been studied. Here, we identify a widely distributed bacterial gene cluster that encodes a pathway for uric acid degradation. Stable isotope tracing demonstrates that gut bacteria metabolize uric acid to xanthine or short chain fatty acids. Ablation of the microbiota in uricase-deficient mice causes severe hyperuricemia, and anaerobe-targeted antibiotics increase the risk of gout in humans. These data reveal a role for the gut microbiota in uric acid excretion and highlight the potential for microbiome-targeted therapeutics in hyperuricemia.

Originele taal-2	Engels
Pagina's (van-tot)	3400-3413.e20
Tijdschrift	Cell
Volume	186
Nummer van het tijdschrift	16
DOI's	https://doi.org/10.1016/j.cell.2023.06.010
Status	Gepubliceerd - 03 aug. 2023

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10.1016/j.cell.2023.06.010

Liu et al 2023 AAMAccepted author manuscript, 967 KBLicentie: CC BY-NC-ND
Liu et al 2023Final published version, 6,19 MB

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Liu, Y., Jarman, J. B., Low, Y. S., Augustijn, H. E., Huang, S., Chen, H., DeFeo, M. E., Sekiba, K., Hou, B. H., Meng, X., Weakley, A. M., Cabrera, A. V., Zhou, Z., van Wezel, G., Medema, M. H., Ganesan, C., Pao, A. C., Gombar, S., & Dodd, D. (2023). A widely distributed gene cluster compensates for uricase loss in hominids. Cell, 186(16), 3400-3413.e20. https://doi.org/10.1016/j.cell.2023.06.010

@article{1a6f9c34cc1b4c60ab0631b7ce3fe247,

title = "A widely distributed gene cluster compensates for uricase loss in hominids",

abstract = "Approximately 15% of US adults have circulating levels of uric acid above its solubility limit, which is causally linked to the disease gout. In most mammals, uric acid elimination is facilitated by the enzyme uricase. However, human uricase is a pseudogene, having been inactivated early in hominid evolution. Though it has long been known that uric acid is eliminated in the gut, the role of the gut microbiota in hyperuricemia has not been studied. Here, we identify a widely distributed bacterial gene cluster that encodes a pathway for uric acid degradation. Stable isotope tracing demonstrates that gut bacteria metabolize uric acid to xanthine or short chain fatty acids. Ablation of the microbiota in uricase-deficient mice causes severe hyperuricemia, and anaerobe-targeted antibiotics increase the risk of gout in humans. These data reveal a role for the gut microbiota in uric acid excretion and highlight the potential for microbiome-targeted therapeutics in hyperuricemia.",

keywords = "gout, hyperuricemia, microbiome, microbiota, uric acid, uricase, Gout/genetics, Humans, Hominidae/genetics, Urate Oxidase/genetics, Animals, Hyperuricemia/genetics, Mammals/metabolism, Adult, Uric Acid/metabolism, Mice, Evolution, Molecular",

author = "Yuanyuan Liu and Jarman, {J. Bryce} and Low, {Yen S.} and Augustijn, {Hannah E.} and Steven Huang and Haoqing Chen and DeFeo, {Mary E.} and Kazuma Sekiba and Hou, {Bi Huei} and Xiandong Meng and Weakley, {Allison M.} and Cabrera, {Ashley V.} and Zhiwei Zhou and {van Wezel}, Gilles and Medema, {Marnix H.} and Calyani Ganesan and Pao, {Alan C.} and Saurabh Gombar and Dylan Dodd",

note = "Data archiving: no NIOO data",

year = "2023",

month = aug,

day = "3",

doi = "10.1016/j.cell.2023.06.010",

language = "English",

volume = "186",

pages = "3400--3413.e20",

journal = "Cell",

issn = "0092-8674",

publisher = "Elsevier B.V.",

number = "16",

}

Liu, Y, Jarman, JB, Low, YS, Augustijn, HE, Huang, S, Chen, H, DeFeo, ME, Sekiba, K, Hou, BH, Meng, X, Weakley, AM, Cabrera, AV, Zhou, Z, van Wezel, G, Medema, MH, Ganesan, C, Pao, AC, Gombar, S & Dodd, D 2023, 'A widely distributed gene cluster compensates for uricase loss in hominids', Cell, vol. 186, nr. 16, blz. 3400-3413.e20. https://doi.org/10.1016/j.cell.2023.06.010

TY - JOUR

T1 - A widely distributed gene cluster compensates for uricase loss in hominids

AU - Liu, Yuanyuan

AU - Jarman, J. Bryce

AU - Low, Yen S.

AU - Augustijn, Hannah E.

AU - Huang, Steven

AU - Chen, Haoqing

AU - DeFeo, Mary E.

AU - Sekiba, Kazuma

AU - Hou, Bi Huei

AU - Meng, Xiandong

AU - Weakley, Allison M.

AU - Cabrera, Ashley V.

AU - Zhou, Zhiwei

AU - van Wezel, Gilles

AU - Medema, Marnix H.

AU - Ganesan, Calyani

AU - Pao, Alan C.

AU - Gombar, Saurabh

AU - Dodd, Dylan

N1 - Data archiving: no NIOO data

PY - 2023/8/3

Y1 - 2023/8/3

N2 - Approximately 15% of US adults have circulating levels of uric acid above its solubility limit, which is causally linked to the disease gout. In most mammals, uric acid elimination is facilitated by the enzyme uricase. However, human uricase is a pseudogene, having been inactivated early in hominid evolution. Though it has long been known that uric acid is eliminated in the gut, the role of the gut microbiota in hyperuricemia has not been studied. Here, we identify a widely distributed bacterial gene cluster that encodes a pathway for uric acid degradation. Stable isotope tracing demonstrates that gut bacteria metabolize uric acid to xanthine or short chain fatty acids. Ablation of the microbiota in uricase-deficient mice causes severe hyperuricemia, and anaerobe-targeted antibiotics increase the risk of gout in humans. These data reveal a role for the gut microbiota in uric acid excretion and highlight the potential for microbiome-targeted therapeutics in hyperuricemia.

AB - Approximately 15% of US adults have circulating levels of uric acid above its solubility limit, which is causally linked to the disease gout. In most mammals, uric acid elimination is facilitated by the enzyme uricase. However, human uricase is a pseudogene, having been inactivated early in hominid evolution. Though it has long been known that uric acid is eliminated in the gut, the role of the gut microbiota in hyperuricemia has not been studied. Here, we identify a widely distributed bacterial gene cluster that encodes a pathway for uric acid degradation. Stable isotope tracing demonstrates that gut bacteria metabolize uric acid to xanthine or short chain fatty acids. Ablation of the microbiota in uricase-deficient mice causes severe hyperuricemia, and anaerobe-targeted antibiotics increase the risk of gout in humans. These data reveal a role for the gut microbiota in uric acid excretion and highlight the potential for microbiome-targeted therapeutics in hyperuricemia.

KW - gout

KW - hyperuricemia

KW - microbiome

KW - microbiota

KW - uric acid

KW - uricase

KW - Gout/genetics

KW - Humans

KW - Hominidae/genetics

KW - Urate Oxidase/genetics

KW - Animals

KW - Hyperuricemia/genetics

KW - Mammals/metabolism

KW - Adult

KW - Uric Acid/metabolism

KW - Mice

KW - Evolution, Molecular

U2 - 10.1016/j.cell.2023.06.010

DO - 10.1016/j.cell.2023.06.010

M3 - Article

C2 - 37541197

AN - SCOPUS:85166599099

SN - 0092-8674

VL - 186

SP - 3400-3413.e20

JO - Cell

JF - Cell

IS - 16

ER -

A widely distributed gene cluster compensates for uricase loss in hominids

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