The quantification of metabolites in blood and urine allows nurses to explore new hypotheses about the microbiome. This review summarizes findings from recent studies with a focus on how the state of the science can influence future nursing research initiatives. Metabolomics can advance nursing research by identifying physiologic/pathophysiologic processes underlying patients’ symptoms and can be useful for testing the effects of nursing interventions. To date, metabolomics has been used to study cardiovascular, respiratory, endocrine, autoimmune, and infectious conditions, with research focused on understanding the microbial metabolism of substrates resulting in circulating/excreted biomarkers such as trimethylamine N-oxide. This review provides specific recommendations for the collection of specimens and goals for future studies.
AminA. M.MostafaH.ArifN. H.Abdul KaderM. A. S.Kah HayY. (2019). Metabolomics profiling and pathway analysis of human plasma and urine reveal further insights into the multifactorial nature of coronary artery disease. Clinica Chimica Acta, 493, 112–122. https://doi.org/10.1016/j.cca.2019.02.030
2.
AnesiA.RubertJ.OluwagbemigunK.Orozco-RuizX.NöthlingsU.BretelerM. M. B.MattiviF. (2019). Metabolic profiling of human plasma and urine, targeting tryptophan, tyrosine and branched chain amino acid pathways. Metabolites, 9, E261. https://doi.org/10.3390/metabo9110261
3.
BaxterN. T.SchmidtA. W.VenkataramanA.KimK. S.WaldronC.SchmidtT. M. (2019). Dynamics of human gut microbiota and short-chain fatty acids in response to dietary interventions with three fermentable fibers. MBio, 10, e02566–18. https://doi.org/10.1128/mBio.02566-18
4.
BellocchiC.Fernández-OchoaÁ.MontanelliG.VigoneB.SantanielloA.MilaniC.Quirantes-PinéR.Borrás-LinaresI.VenturaM.Segura-CarretteroA.Alarcón-RiquelmeM. E.BerettaL. (2018). Microbial and metabolic multi-omic correlations in systemic sclerosis patients. Annals of the New York Academy of Sciences, 1421, 97–109. https://doi.org/10.1111/nyas.13736
5.
BugautM. (1987). Occurrence, absorption and metabolism of short chain fatty acids in the digestive tract of mammals. Comparative Biochemistry and Physiology Part B: Comparative Biochemistry, 86(3), 439–472.
6.
ChenM. X.WangS. Y.KuoC. H.TsaiI. L. (2019). Metabolome analysis for investigating host-gut microbiota interactions. Journal of the Formosan Medical Association, 118, S10–S22. https://doi.org/10.1016/j.jfma.2018.09.007
7.
Chhibber-GoelJ.SinghalV.ParakhN.BhargavaB.SharmaA. (2017). The metabolite trimethylamine-N-oxide is an emergent biomarker of human health. Current Medicinal Chemistry, 24, 3942–3953. https://doi.org/10.2174/0929867323666160830104025
8.
ConnorsJ.DaweN.Van LimbergenJ. (2018). The role of succinate in the regulation of intestinal inflammation. Nutrients, 11, E25. https://doi.org/10.3390/nu11010025
9.
DaliriE. B.WeiS.OhD. H.LeeB. H. (2017). The human microbiome and metabolomics: Current concepts and applications. Critical Reviews in Food Science and Nutrition, 57, 3565–3576. https://doi.org/10.1080/10408398.2016.1220913
HayashiT.YamashitaT.WatanabeH.KamiK.YoshidaN.TabataT.EmotoT.SasakiN.MizoguchiT.IrinoY.TohR.ShinoharaM.OkadaY.OgawaW.YamadaT.HirataK. I. (2018). Gut microbiome and plasma microbiome-related metabolites in patients with decompensated and compensated heart failure. Circulation Journal, 83, 182–192. https://doi.org/10.1253/circj.CJ-18-0468
12.
HuttenhowerC.GeversD.KnightR.AbubuckerS.BadgerJ. H.ChinwallaA. T.CreasyH. H.EarlA. M.FitzgeraldM. G.FultonR. S.GiglioM. G.Hallsworth-PepinK.LobosE. A.MadupuR.MagriniV.MartinJ. C.MitrevaM.MuznyD. M.SodergrenE. J.…WhiteO. (2012). Structure, function and diversity of the healthy human microbiome. Nature, 486, 207–214. https://doi.org/10.1038/nature11234
13.
JobardE.TredanO.PostolyD.AndreF.MartinA. L.Elena-HerrmannB.BoyaultS. (2016). A systematic evaluation of blood serum and plasma pre-analytics for metabolomics cohort studies. International Journal of Molecular Sciences, 17, E2035. https://doi.org/10.3390/ijms17122035
14.
LiP.ZhongC.LiS.SunT.HuangH.ChenX.ZhuY.HuX.PengX.ZhangX.BaoW.ShanZ.ChengJ.HuF. B.YangN.LiuL. (2018). Plasma concentration of trimethylamine-N-oxide and risk of gestational diabetes mellitus. American Journal of Clinical Nutrition, 108, 603–610. https://doi.org/10.1093/ajcn/nqy116
15.
LiuF.LingZ.XiaoY.XiaoY.LvL.YangQ.WangB.LuH.ZhengL.JiangP.WangW.LiL. (2017). Dysbiosis of urinary microbiota is positively correlated with type 2 diabetes mellitus. Oncotarget, 8, 3798–3810. https://doi.org/10.18632/oncotarget.14028
16.
LiuR.HongJ.XuX.FengQ.ZhangD.GuY.ShiJ.ZhaoS.LiuW.WangX.XiaH.LiuZ.CuiB.LiangP.XiL.JinJ.YingX.WangX.ZhaoX.…WangW. (2017). Gut microbiome and serum metabolome alterations in obesity and after weight-loss intervention. Nature Medicine, 23, 859–868. https://doi.org/10.1038/nm.4358
17.
LiuX.XieZ.SunM.WangX.LiJ.CuiJ.ZhangF.YinL.HuangD.HouJ.TianJ.YuB. (2018). Plasma trimethylamine N-oxide is associated with vulnerable plaque characteristics in CAD patients as assessed by optical coherence tomography. International Journal of Cardiology, 265, 18–23. https://doi.org/10.1016/j.ijcard.2018.04.126
18.
MakiK. A.DialloA. F.LockwoodM. B.FranksA. T.GreenS. J.JosephP. V. (2018). Considerations when designing a microbiome study: Implications for nursing science. Biological Research for Nursing, 21, 125–141. https://doi.org/10.1177/1099800418811639
MissailidisC.NeogiU.StenvinkelP.TrøseidM.NowakP.BergmanP. (2018). The microbial metabolite trimethylamine-N-oxide in association with inflammation and microbial dysregulation in three HIV cohorts at various disease stages. AIDS, 32, 1589–1598. https://doi.org/10.1097/QAD.0000000000001813
21.
MoonJ. Y.ZolnikC. P.WangZ. (2018). Gut microbiota and plasma metabolites associated with diabetes in women with, or at high risk for, HIV infection. EBioMedicine, 37, 392–400.
22.
NieJ.XieL.ZhaoB. X.LiY.QiuB.ZhuF.LiG. F.HeM.WangY.WangB.LiuS.ZhangH.GuoH.CaiY.HuoY.HouF. F.XuX.QinX. (2018). Serum trimethylamine N-oxide concentration is positively associated with first stroke in hypertensive patients. Stroke, 49, 2021–2028. https://doi.org/10.1161/STROKEAHA
23.
NowińskiA.UfnalM. (2018). Trimethylamine N-oxide: A harmful, protective or diagnostic marker in lifestyle diseases?Nutrition, 46, 7–12. https://doi.org/10.1016/j.nut.2017.08.001
24.
OttigerM.NicklerM.SteuerC.BernasconiL.HuberA.Christ-CrainM.HenzenC.HoessC.ThomannR.ZimmerliW.MuellerB.SchuetzP. (2018). Gut, microbiota-dependent trimethylamine-N-oxide is associated with long-term all-cause mortality in patients with exacerbated chronic obstructive pulmonary disease. Nutrition, 45, 135–141. https://doi.org/10.1016/j.nut.2017.07.001
25.
OttossonF.BrunkwallL.EricsonU.NilssonP. M.AlmgrenP.FernandezC.MelanderO.Orho-MelanderM. (2018). Connection between BMI-related plasma metabolite profile and gut microbiota. Journal of Clinical Endocrinology and Metabolism, 103, 1491–1501. https://doi.org/10.1210/jc.2017-02114
26.
PavlovaT.VidovaV.Bienertova-VaskuJ.JankuP.AlmasiM.KlanovaJ.SpacilZ. (2017). Urinary intermediates of tryptophan as indicators of the gut microbial metabolism. Analytica Chimica Acta, 987, 72–80. https://doi.org/10.1016/j.aca.2017.08.022
27.
SerenaC.Ceperuelo-MallafréV.KeiranN.Queipo-OrtuñoM. I.BernalR.Gomez-HuelgasR.Urpi-SardaM.SabaterM.Pérez-BrocalV.Andrés-LacuevaC.MoyaA.TinahonesF. J.Fernández-RealJ. M.VendrellJ.Fernández-VeledoS. (2018). Elevated circulating levels of succinate in human obesity are linked to specific gut microbiota. Multidisciplinary Journal of Microbial Ecology, 12, 1642–1657. https://doi.org/10.1038/s41396-018-0068-2
28.
ShanZ.ClishC. B.HuaS.ScottJ. M.HannaD. B.BurkR. D.HaberlenS. A.ShahS. J.MargolickJ. B.SearsC. L.PostW. S.LandayA. L.LazarJ. M.HodisH. N.AnastosK.KaplanR. C.QiQ. (2018). Gut microbial-related choline metabolite trimethylamine-N-oxide is associated with progression of carotid artery atherosclerosis in HIV infection. Journal of Infectious Diseases, 218, 1474–1479. https://doi.org/10.1093/infdis/jiy356
29.
TuomainenM.LindströmJ.LehtonenM.AuriolaS.PihlajamäkiJ.PeltonenM.TuomilehtoJ.UusitupaM.de MelloV. D.HanhinevaK. (2018). Associations of serum indolepropionic acid, a gut microbiota metabolite, with type 2 diabetes and low-grade inflammation in high-risk individuals. Nutrition & Diabetes, 8, 35. https://doi.org/10.1038/s41387-018-0046-9
30.
Urpi-SardaM.Almanza-AguileraE.LlorachR.Vázquez-FresnoR.EstruchR.CorellaD.SorliJ. V.CarmonaF.Sanchez-PlaA.Salas-SalvadóJ.Andres-LacuevaC. (2019). Non-targeted metabolomic biomarkers and metabotypes of type 2 diabetes: A cross-sectional study of PREDIMED trial participants. Diabetes & Metabolism, 45, 167–174. https://doi.org/10.1016/j.diabet.2018.02.006
31.
VelasquezM. T.RamezaniA.ManalA.RajD. S. (2016). Trimethylamine N-oxide: The good, the bad and the unknown. Toxins, 8, E326. https://doi.org/10.3390/toxins8110326
32.
WalejkoJ. M.KimS.GoelR.HandbergE. M.RichardsE. M.PepineC. J.RaizadaM. K. (2018). Gut microbiota and serum metabolite differences in African Americans and White Americans with high blood pressure. International Journal of Cardiology, 271, 336–339. https://doi.org/10.1016/j.ijcard.2018.04.074
33.
WangZ.UsykM.SollecitoC. C. (2019). Altered gut microbiota and host metabolite profiles in HIV-infected women. Clinical Infectious Diseases, ciz1117. https://doi.org/10.1093/cid/ciz1117
ZhaiQ.WangX.ChenC.TangY.WangY.TianJ.ZhaoY.LiuX. (2019). Prognostic value of plasma trimethylamine N-oxide levels in patients with acute ischemic stroke. Cellular and Molecular Neurobiology, 39, 1201–1206. https://doi.org/10.1007/s10571-019-00714-3
36.
ZhuC.LiG.LvZ. (2020). Association of plasma trimethylamine-N-oxide levels with post-stroke cognitive impairment: A 1-year longitudinal study. Neurological Sciences, 41, 57–63. https://doi.org/10.1007/s10072-019-04040-w
