@article{fdi:010088590,
  title = {{E}vidence of a causal and modifiable relationship between kidney function and circulating trimethylamine {N}-oxide},
  author = {{A}ndrikopoulos, {P}. and {A}ron-{W}isnewsky, {J}. and {C}hakaroun, {R}. and {M}yridakis, {A}. and {F}orslund, {S}. {K}. and {N}ielsen, {T}. and {A}driouch, {S}. and {H}olmes, {B}. and {C}hilloux, {J}. and {V}ieira-{S}ilva, {S}. and {F}alony, {G}. and {S}alem, {J}. {E}. and {A}ndreelli, {F}. and {B}elda, {E}. and {K}ieswich, {J}. and {C}hechi, {K}. and {P}uig-{C}astellvi, {F}. and {C}hevalier, {M}. and {L}e {C}hatelier, {E}. and {O}lanipekun, {M}. {T}. and {H}oyles, {L}. and {A}lves, {R}. and {H}elft, {G}. and {I}snard, {R}. and {K}ober, {L}. and {C}oelho, {L}. {P}. and {R}ouault, {C}. and {G}auguier, {D}. and {G}otze, {J}. {P}. and {P}rifti, {E}di and {F}roguel, {P}. and {Z}ucker, {J}ean-{D}aniel and {B}äckhed, {F}. and {V}estergaard, {H}. and {H}ansen, {T}. and {O}ppert, {J}. {M}. and {B}lüher, {M}. and {N}ielsen, {J}. and {R}aes, {J}. and {B}ork, {P}. and {Y}aqoob, {M}. {M}. and {S}tumvoll, {M}. and {P}edersen, {O}. and {E}hrlich, {S}. {D}. and {C}l{\'e}ment, {K}. and {D}umas, {M}. {E}. and {M}eta{C}ardis {C}onsortium,},
  editor = {},
  language = {{ENG}},
  abstract = {{T}he host-microbiota co-metabolite trimethylamine {N}-oxide ({TMAO}) is linked to increased cardiovascular risk but how its circulating levels are regulated remains unclear. {W}e applied "explainable" machine learning, univariate, multivariate and mediation analyses of fasting plasma {TMAO} concentration and a multitude of phenotypes in 1,741 adult {E}uropeans of the {M}eta{C}ardis study. {H}ere we show that next to age, kidney function is the primary variable predicting circulating {TMAO}, with microbiota composition and diet playing minor, albeit significant, roles. {M}ediation analysis suggests a causal relationship between {TMAO} and kidney function that we corroborate in preclinical models where {TMAO} exposure increases kidney scarring. {C}onsistent with our findings, patients receiving glucose-lowering drugs with reno-protective properties have significantly lower circulating {TMAO} when compared to propensity-score matched control individuals. {O}ur analyses uncover a bidirectional relationship between kidney function and {TMAO} that can potentially be modified by reno-protective anti-diabetic drugs and suggest a clinically actionable intervention for decreasing {TMAO}-associated excess cardiovascular risk. {TMAO} is known to be atherothrombotic. {H}ere the authors show that i) kidney function is the main determinant of serum {TMAO}, ii) {TMAO} increases kidney scarring with {TGF}-beta 1 signalling and iii) anti-diabetic drugs with reno-protective properties such as {GLP}1{R} agonists reduce plasma {TMAO}.},
  keywords = {{EUROPE}},
  booktitle = {},
  journal = {{N}ature {C}ommunications},
  volume = {14},
  numero = {1},
  pages = {5843 [18 p.]},
  year = {2023},
  DOI = {10.1038/s41467-023-39824-4},
  URL = {https://www.documentation.ird.fr/hor/fdi:010088590},
}