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Microbiota metabolites affect sleep as drivers of brain‑gut communication (Review)

  • Authors:
    • Hanxing Cheng
    • Wanying Yang
    • Huaiyi Xu
    • Wenwen Zhu
    • Ailin Gong
    • Xuemei Yang
    • Sen Li
    • Houping Xu
  • View Affiliations / Copyright

    Affiliations: Geriatric Department, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China, Department of Orthopedic Surgery, Division of Spine Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu 210000, P.R. China
    Copyright: © Cheng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 130
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    Published online on: June 30, 2025
       https://doi.org/10.3892/ijmm.2025.5571
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Abstract

Sleep plays a crucial role in maintaining and improving physical and mental health. However, the prevalence of sleep disorders is increasing in modern society. Recently, the gut‑brain axis has emerged as a prominent focus within the realm of sleep disorder research, with gut microbiota metabolites serving as essential factors in gut‑brain communication. The present study summarizes the emerging connections between gut microbiota metabolites and sleep, mainly focusing on those derived from tryptophan and dietary fiber metabolism. It discusses potential pathways and molecular processes by which sleep interacts with the gut microbiota metabolites, aiming to evaluate the feasibility of using gut microbiota interventions to treat sleep disorders.
View Figures

Figure 1

Three key connecting pathways in the
brain-gut-microbiota system. Metabolites of gut microbiota,
together with neurotransmitters such as 5-HT and GABA, act as
chemical signals. They can cross the BBB to enter the brain.
Secondly, they can activate the vagus nerve through EECs and
enteric neurons, transmitting signals to the nucleus of the
solitary tract in the brainstem, thus influencing brain functions.
In addition, they can regulate immune cells to release cytokines,
which are involved in the transmission of signals to the brain
indirectly via the bloodstream. Figure support was provided by
Figdraw. 5-HT, serotonin; BBB, blood-brain barrier; CNS, central
nervous system; TH1, helper T 1 cells; TH2, helper T 2 cells; Treg,
regulatory T cells; EECs, enteroendocrine cells.

Figure 2

Inhibition of the activation of the
TLR4/NF-κB signaling pathway. Sleep deprivation impairs the gut by
reducing the expression of tight junction proteins (occludin and
ZO-1, increasing intestinal permeability and allowing the leakage
of bacterial lipopolysaccharides, peptidoglycans,
pathogen-associated molecules and inflammatory factors into the
bloodstream. This activates the TLR4/NF-κB pathway, triggering
systemic inflammation and neuroinflammation. However, gut
microbiota-derived metabolites can inhibit the activation of the
TLR4/NF-κB pathway. Figure support was provided by Figdraw. ZO-1,
zonula occludens-1; TLR, Toll-like receptor; MyD88, myeloid
differentiation factor 88; IKK, IκB kinase; NF-κB, nuclear
factor-κB; LPS, lipopolysaccharide; PAMPs, pathogen-associated
molecular patterns; IL, interleukin; SCFA, short chain fatty
acid.

Figure 3

Indole metabolites induce
neuroinflammation through the AHR and NTS pathways. Gut microbiota
metabolites derived from tryptophan can transmit signals through
the AHR in microglia, activate TGF-α, and then exert
neuroprotective effects via the ErbB1 receptor in astrocytes. They
can also inhibit VEGF-β, thereby suppressing the neuroinflammation
caused by the activation of Flt-1. Moreover, IFN-I-signaling in
astrocytes collaborates with TPH microbial metabolites to
co-activate the AHR, inducing the expression of Socs2, which in
turn inhibits the activation of NF-κB and alleviates inflammation.
Meanwhile, these metabolites can bidirectionally regulate the
release of the appetite hormone GLP-1, enhance BDNF in the brain,
and send signals to the brain circuits and the nucleus tractus
solitarius. Figure support was provided by Figdraw. AHR, aryl
hydrocarbon receptor; TGF-α, transforming growth factor-α; ErbB1,
epidermal growth factor; VEGF-β, vascular endothelial growth
factor-β; Flt-1, Fms-like tyrosine kinase 1; IFN-I, type I
interferon; TPH, tryptophan hydroxylase; Socs2, suppressor of
cytokine signaling 2; NF-κB, nuclear factor-κB; GLP-1,
glucagon-like peptide-1; BDNF, brain-derived neurotrophic factor;
NTS, nucleus tractus solitarius; CNS, central nervous system; IAA,
indole-3-acetic acid; IS, indoxyl sulfate; IPA, indole-3-propionic
acid; I3A, indole-3-aldehyde; IAld, Indole-3-acetaldehyde; I3S,
indole-3-sulfonic acid; L cell, Enteroendocrine L cells.

Figure 4

Mechanisms of indole and SCFAs
affecting the circadian clock. SCFAs such as butyrate, propionate
and isovalerate strongly inhibit the activity of HDAC, increase the
level of histone acetylation, and promote the activation of
downstream circadian clock genes. They may also activate SCFA
receptor genes (such as FFAR2) in the cecal wall, further providing
feedback and enhancing both peripheral and central rhythms. In
addition, butyrate can increase the number of NR1D1, which is a
core component of the molecular circadian clock. On the other hand,
gut microbiota metabolites derived from tryptophan may activate the
AHR, indirectly interfering with the transcriptional activity of
BMAL/CLOCK proteins and disrupting the circadian rhythm. Figure
support was provided by Figdraw. SCFAs, short-chain fatty acids;
HDAC, histone deacetylase; NR1D1, Nuclear receptor subfamily 1
group D member 1; AHR, aryl hydrocarbon receptor; Bmal1, brain and
muscle ARNT-like 1; CLOCK, circadian locomotor output cycles kaput;
cBMAL, chicken brain and muscle ARNT-like 1; NFIL3, nuclear factor,
interleukin 3 regulated; FFAR2, free fatty acid receptor 2.
View References

1 

Lund HG, Reider BD, Whiting AB and Prichard JR: Sleep patterns and predictors of disturbed sleep in a large population of college students. J Adolesc Health. 46:124–132. 2010. View Article : Google Scholar : PubMed/NCBI

2 

Bishir M, Bhat A, Essa MM, Ekpo O, Ihunwo AO, Veeraraghavan VP, Mohan SK, Mahalakshmi AM, Ray B, Tuladhar S, et al: Sleep deprivation and neurological disorders. Biomed Res Int. 2020:57640172020. View Article : Google Scholar :

3 

Palagini L, Hertenstein E, Riemann D and Nissen C: Sleep, insomnia and mental health. J Sleep Res. 31:e136282022. View Article : Google Scholar : PubMed/NCBI

4 

Chang L, Wei Y and Hashimoto K: Brain-gut-microbiota axis in depression: A historical overview and future directions. Brain Res Bull. 182:44–56. 2022. View Article : Google Scholar : PubMed/NCBI

5 

Gossard TR, Trotti LM, Videnovic A and St Louis EK: Restless legs syndrome: Contemporary diagnosis and treatment. Neurotherapeutic. 18:140–155. 2021. View Article : Google Scholar

6 

Sun SY and Chen GH: Treatment of circadian rhythm sleep-wake disorders. Curr Neuropharmacol. 20:1022–1034. 2022. View Article : Google Scholar

7 

Arnulf I, Thomas R, Roy A and Dauvilliers Y: Update on the treatment of idiopathic hypersomnia: Progress, challenges, and expert opinion. Sleep Med Rev. 69:1017662023. View Article : Google Scholar : PubMed/NCBI

8 

You M, Chen N, Yang Y, Cheng L, He H, Cai Y, Liu Y, Liu H and Hong G: The gut microbiota-brain axis in neurological disorders. MedComm (2020). 5:e6562024. View Article : Google Scholar : PubMed/NCBI

9 

Haarhuis JE, Kardinaal A and Kortman GAM: Probiotics, prebiotics and postbiotics for better sleep quality: A narrative review. Benef Microbes. 13:169–182. 2022. View Article : Google Scholar : PubMed/NCBI

10 

Singh V, Yeoh BS, Chassaing B, Xiao X, Saha P, Aguilera Olvera R, Lapek JD Jr, Zhang L, Wang WB, Hao S, et al: Dysregulated microbial fermentation of soluble fiber induces cholestatic liver cancer. Cell. 175:679–694.e22. 2018. View Article : Google Scholar : PubMed/NCBI

11 

Barrett E, Ross RP, O'Toole PW, Fitzgerald GF and Stanton C: γ-Aminobutyric acid production by culturable bacteria from the human intestine. J Appl Microbiol. 113:411–417. 2012. View Article : Google Scholar : PubMed/NCBI

12 

Chen H, Nwe PK, Yang Y, Rosen CE, Bielecka AA, Kuchroo M, Cline GW, Kruse AC, Ring AM, Crawford JM and Palm NW: A forward chemical genetic screen reveals gut microbiota metabolites that modulate host physiology. Cell. 177:1217–1231.e18. 2019. View Article : Google Scholar : PubMed/NCBI

13 

Ren Z, Zhang R, Li Y, Li Y, Yang Z and Yang H: Ferulic acid exerts neuroprotective effects against cerebral ischemia/reperfusion-induced injury via antioxidant and anti-apoptotic mechanisms in vitro and in vivo. Int J Mol Med. 40:1444–1456. 2017. View Article : Google Scholar : PubMed/NCBI

14 

Verzelloni E, Pellacani C, Tagliazucchi D, Tagliaferri S, Calani L, Costa LG, Brighenti F, Borges G, Crozier A, Conte A and Del Rio D: Antiglycative and neuroprotective activity of colon-derived polyphenol catabolites. Mol Nutr Food Res. 55(Suppl 1): S35–S43. 2011. View Article : Google Scholar : PubMed/NCBI

15 

Mao JH, Kim YM, Zhou YX, Hu D, Zhong C, Chang H, Brislawn CJ, Fansler S, Langley S, Wang Y, et al: Genetic and metabolic links between the murine microbiome and memory. Microbiome. 8:532020. View Article : Google Scholar : PubMed/NCBI

16 

Ahmed H, Leyrolle Q, Koistinen V, Kärkkäinen O, Layé S, Delzenne N and Hanhineva K: Microbiota-derived metabolites as drivers of gut-brain communication. Gut Microbes. 14:21028782022. View Article : Google Scholar : PubMed/NCBI

17 

Mann ER, Lam YK and Uhlig HH: Short-chain fatty acids: Linking diet, the microbiome and immunity. Nat Rev Immunol. 24:577–595. 2024. View Article : Google Scholar : PubMed/NCBI

18 

Agus A, Clément K and Sokol H: Gut microbiota-derived metabolites as central regulators in metabolic disorders. Gut. 70:1174–1182. 2021. View Article : Google Scholar

19 

Ganz J: Revealing the complexity of the gut's brain. Nat Neurosci. 24:1–2. 2021. View Article : Google Scholar

20 

Margolis KG, Cryan JF and Mayer EA: The microbiota-gut-brain axis: From motility to mood. Gastroenterology. 160:1486–1501. 2021. View Article : Google Scholar : PubMed/NCBI

21 

Niesler B, Kuerten S, Demir IE and Schäfer KH: Disorders of the enteric nervous system-a holistic view. Nat Rev Gastroenterol Hepatol. 18:393–410. 2021. View Article : Google Scholar : PubMed/NCBI

22 

Bonaz B, Bazin T and Pellissier S: The vagus nerve at the interface of the microbiota-gut-brain axis. Front Neurosci. 12:492018. View Article : Google Scholar : PubMed/NCBI

23 

Agirman G, Yu KB and Hsiao EY: Signaling inflammation across the gut-brain axis. Science. 374:1087–1092. 2021. View Article : Google Scholar : PubMed/NCBI

24 

Zielinski MR and Gibbons AJ: Neuroinflammation, sleep, and circadian rhythms. Front Cell Infect Microbiol. 12:8530962022. View Article : Google Scholar : PubMed/NCBI

25 

Grigg JB and Sonnenberg GF: Host-microbiota interactions shape local and systemic inflammatory diseases. J Immunol. 198:564–571. 2017. View Article : Google Scholar : PubMed/NCBI

26 

Salvo-Romero E, Stokes P and Gareau MG: Microbiota-immune interactions: From gut to brain. Lymphosign J. 7:1–23. 2020. View Article : Google Scholar

27 

Zheng D, Liwinski T and Elinav E: Interaction between microbiota and immunity in health and disease. Cell Res. 30:492–506. 2020. View Article : Google Scholar : PubMed/NCBI

28 

Averina OV, Zorkina YA, Yunes RA, Kovtun AS, Ushakova VM, Morozova AY, Kostyuk GP, Danilenko VN and Chekhonin VP: Bacterial metabolites of human gut microbiota correlating with depression. Int J Mol Sci. 21:92342020. View Article : Google Scholar : PubMed/NCBI

29 

Parker A, Fonseca S and Carding SR: Gut microbes and metabolites as modulators of blood-brain barrier integrity and brain health. Gut Microbes. 11:135–157. 2020. View Article : Google Scholar :

30 

Dalile B, Van Oudenhove L, Vervliet B and Verbeke K: The role of short-chain fatty acids in microbiota-gut-brain communication. Nat Rev Gastroenterol Hepatol. 16:461–478. 2019. View Article : Google Scholar : PubMed/NCBI

31 

Gibson JA, Sladen GE and Dawson AM: Protein absorption and ammonia production: The effects of dietary protein and removal of the colon. Br J Nutr. 35:61–65. 1976. View Article : Google Scholar : PubMed/NCBI

32 

Tan JK, Macia L and Mackay CR: Dietary fiber and SCFAs in the regulation of mucosal immunity. J Allergy Clin Immunol. 151:361–370. 2023. View Article : Google Scholar

33 

Fock E and Parnova R: Mechanisms of blood-brain barrier protection by microbiota-derived short-chain fatty acids. Cells. 12:6572023. View Article : Google Scholar : PubMed/NCBI

34 

Ikeda T, Nishida A, Yamano M and Kimura I: Short-chain fatty acid receptors and gut microbiota as therapeutic targets in metabolic, immune, and neurological diseases. Pharmacol Ther. 239:1082732022. View Article : Google Scholar : PubMed/NCBI

35 

Li Y, Shao L, Mou Y, Zhang Y and Ping Y: Sleep, circadian rhythm and gut microbiota: Alterations in Alzheimer's disease and their potential links in the pathogenesis. Gut Microbes. 13:19574072021. View Article : Google Scholar : PubMed/NCBI

36 

Zhu R, Fang Y, Li H, Liu Y, Wei J, Zhang S, Wang L, Fan R, Wang L, Li S and Chen T: Psychobiotic Lactobacillus plantarum JYLP-326 relieves anxiety, depression, and insomnia symptoms in test anxious college via modulating the gut microbiota and its metabolism. Front Immunol. 14:11581372023. View Article : Google Scholar : PubMed/NCBI

37 

Li Y, Zhang B, Zhou Y, Wang D, Liu X, Li L, Wang T, Zhang Y, Jiang M, Tang H, et al: Gut microbiota changes and their relationship with inflammation in patients with acute and chronic insomnia. Nat Sci Sleep. 12:895–905. 2020. View Article : Google Scholar : PubMed/NCBI

38 

Shimizu Y, Yamamura R, Yokoi Y, Ayabe T, Ukawa S and Nakamura K, Okada E, Imae A, Nakagawa T, Tamakoshi A and Nakamura K: Shorter sleep time relates to lower human defensin 5 secretion and compositional disturbance of the intestinal microbiota accompanied by decreased short-chain fatty acid production. Gut Microbes. 15:21903062023. View Article : Google Scholar : PubMed/NCBI

39 

Zuraikat FM, Wood RA, Barragán R and St-Onge MP: Sleep and diet: Mounting evidence of a cyclical relationship. Annu Rev Nutr. 41:309–332. 2021. View Article : Google Scholar : PubMed/NCBI

40 

Wikoff WR, Anfora AT, Liu J, Schultz PG, Lesley SA, Peters EC and Siuzdak G: Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites. Proc Natl Acad Sci USA. 106:3698–3703. 2009. View Article : Google Scholar : PubMed/NCBI

41 

Dicks LMT: Gut bacteria and neurotransmitters. Microorganisms. 10:18382022. View Article : Google Scholar : PubMed/NCBI

42 

Liu N, Sun S, Wang P, Sun Y, Hu Q and Wang X: The mechanism of secretion and metabolism of gut-derived 5-hydroxytryptamine. Int J Mol Sci. 22:79312021. View Article : Google Scholar : PubMed/NCBI

43 

Gao K, Mu CL, Farzi A and Zhu WY: Tryptophan metabolism: A link between the gut microbiota and brain. Adv Nutr. 11:709–723. 2020. View Article : Google Scholar :

44 

Xie Y, Wang C, Zhao D, Wang C and Li C: Dietary proteins regulate serotonin biosynthesis and catabolism by specific gut microbes. J Agric Food Chem. 68:5880–5890. 2020. View Article : Google Scholar : PubMed/NCBI

45 

Parkar SG, Kalsbeek A and Cheeseman JF: Potential role for the gut microbiota in modulating host circadian rhythms and metabolic health. Microorganisms. 7:412019. View Article : Google Scholar : PubMed/NCBI

46 

Gershon MD and Tack J: The serotonin signaling system: From basic understanding to drug development for functional GI disorders. Gastroenterology. 132:397–414. 2007. View Article : Google Scholar : PubMed/NCBI

47 

Latorre E, Mendoza C, Matheus N, Castro M, Grasa L, Mesonero JE and Alcalde AI: IL-10 modulates serotonin transporter activity and molecular expression in intestinal epithelial cells. Cytokine. 61:778–784. 2013. View Article : Google Scholar : PubMed/NCBI

48 

Buey B, Forcén A, Grasa L, Layunta E, Mesonero JE and Latorre E: Gut microbiota-derived short-chain fatty acids: Novel regulators of intestinal serotonin transporter. Life (Basel). 13:10852023.PubMed/NCBI

49 

Cai J, Cheung J, Cheung SWM, Chin KTC, Leung RWK, Lam RST, Sharma R, Yiu JHC and Woo CW: Butyrate acts as a positive allosteric modulator of the 5-HT transporter to decrease availability of 5-HT in the ileum. Br J Pharmacol. 181:1654–1670. 2024. View Article : Google Scholar

50 

Dicks LMT: Our mental health is determined by an intrinsic interplay between the central nervous system, enteric nerves, and gut microbiota. Int J Mol Sci. 25:382023. View Article : Google Scholar

51 

Wei L, Singh R and Ghoshal UC: Enterochromaffin cells-gut microbiota crosstalk: Underpinning the symptoms, pathogenesis, and pharmacotherapy in disorders of gut-brain interaction. J Neurogastroenterol Motil. 28:357–375. 2022. View Article : Google Scholar : PubMed/NCBI

52 

Guo X, Yin C, Yang F, Zhang Y, Huang H, Wang J, Deng B, Cai T, Rao Y and Xi R: The cellular diversity and transcription factor code of Drosophila enteroendocrine cells. Cell Rep. 29:4172–4185.e5. 2019. View Article : Google Scholar : PubMed/NCBI

53 

Ye L, Bae M, Cassilly CD, Jabba SV, Thorpe DW, Martin AM, Lu HY, Wang J, Thompson JD, Lickwar CR, et al: Enteroendocrine cells sense bacterial tryptophan catabolites to activate enteric and vagal neuronal pathways. Cell Host Microbe. 29:179–196.e9. 2021. View Article : Google Scholar :

54 

Gao T, Wang Z, Cao J, Dong Y and Chen Y: Melatonin alleviates oxidative stress in sleep deprived mice: Involvement of small intestinal mucosa injury. Int Immunopharmacol. 78:1060412020. View Article : Google Scholar

55 

Gao T, Wang Z, Dong Y, Cao J, Lin R, Wang X, Yu Z and Chen Y: Role of melatonin in sleep deprivation-induced intestinal barrier dysfunction in mice. J Pineal Res. 67:e125742019. View Article : Google Scholar : PubMed/NCBI

56 

Yu H, Lin L, Zhang Z, Zhang H and Hu H: Targeting NF-κB pathway for the therapy of diseases: Mechanism and clinical study. Signal Transduct Target Ther. 5:2092020. View Article : Google Scholar

57 

Wu Z, Liu L, Li L, Cao X, Jia W, Liao X, Zhao Z, Qi H, Fan G, Lu H, et al: Oral nano-antioxidants improve sleep by restoring intestinal barrier integrity and preventing systemic inflammation. Natl Sci Rev. 10:nwad3092023. View Article : Google Scholar

58 

Veler H: Sleep and inflammation: Bidirectional relationship. Sleep Med Clin. 18:213–218. 2023. View Article : Google Scholar : PubMed/NCBI

59 

Yang Y, Gu K, Meng C, Li J, Lu Q, Zhou X, Yan D, Li D, Pei C, Lu Y, et al: Relationship between sleep and serum inflammatory factors in patients with major depressive disorder. Psychiatry Res. 329:1155282023. View Article : Google Scholar : PubMed/NCBI

60 

Wang Z, Chen WH, Li SX, He ZM, Zhu WL, Ji YB, Wang Z, Zhu XM, Yuan K, Bao YP, et al: Gut microbiota modulates the inflammatory response and cognitive impairment induced by sleep deprivation. Mol Psychiatry. 26:6277–6292. 2021. View Article : Google Scholar : PubMed/NCBI

61 

Su H, Zhang C, Zou X, Lu F, Zeng Y, Guan H, Ren Y, Yuan F, Xu L, Zhang M and Dong H: Jiao-tai-wan inhibits inflammation of the gut-brain-axis and attenuates cognitive impairment in insomnic rats. J Ethnopharmacol. 250:1124782020. View Article : Google Scholar

62 

Hergenhan S, Holtkamp S and Scheiermann C: Molecular interactions between components of the circadian clock and the immune system. J Mol Biol. 432:3700–3713. 2020. View Article : Google Scholar : PubMed/NCBI

63 

Zhao Z, Ning J, Bao XQ, Shang M, Ma J, Li G and Zhang D: Fecal microbiota transplantation protects rotenone-induced Parkinson's disease mice via suppressing inflammation mediated by the lipopolysaccharide-TLR4 signaling pathway through the microbiota-gut-brain axis. Microbiome. 9:2262021. View Article : Google Scholar : PubMed/NCBI

64 

McCuaig B and Goto Y: Immunostimulating commensal bacteria and their potential use as therapeutics. Int J Mol Sci. 24:156442023. View Article : Google Scholar : PubMed/NCBI

65 

Mohawk JA, Green CB and Takahashi JS: Central and peripheral circadian clocks in mammals. Annu Rev Neurosci. 35:445–462. 2012. View Article : Google Scholar : PubMed/NCBI

66 

Prinz M, Jung S and Priller J: Microglia biology: One century of evolving concepts. Cell. 179:292–311. 2019. View Article : Google Scholar : PubMed/NCBI

67 

Horng S, Therattil A, Moyon S, Gordon A, Kim K, Argaw AT, Hara Y, Mariani JN, Sawai S, Flodby P, et al: Astrocytic tight junctions control inflammatory CNS lesion pathogenesis. J Clin Invest. 127:3136–3151. 2017. View Article : Google Scholar : PubMed/NCBI

68 

Gudkov SV, Burmistrov DE, Kondakova EV, Sarimov RM, Yarkov RS, Franceschi C and Vedunova MV: An emerging role of astrocytes in aging/neuroinflammation and gut-brain axis with consequences on sleep and sleep disorders. Ageing Res Rev. 83:1017752023. View Article : Google Scholar

69 

Wang X, Wang Z, Cao J, Dong Y and Chen Y: Gut microbiota-derived metabolites mediate the neuroprotective effect of melatonin in cognitive impairment induced by sleep deprivation. Microbiome. 11:172023. View Article : Google Scholar : PubMed/NCBI

70 

Zhang L, Ko CY and Zeng YM: Immunoregulatory effect of short-chain fatty acids from gut microbiota on obstructive sleep apnea-associated hypertension. Nat Sci Sleep. 14:393–405. 2022. View Article : Google Scholar : PubMed/NCBI

71 

Mowat AM and Agace WW: Regional specialization within the intestinal immune system. Nat Rev Immunol. 14:667–685. 2014. View Article : Google Scholar : PubMed/NCBI

72 

Nastasi C, Candela M, Bonefeld CM, Geisler C, Hansen M, Krejsgaard T, Biagi E, Andersen MH, Brigidi P, Ødum N, et al: The effect of short-chain fatty acids on human monocyte-derived dendritic cells. Sci Rep. 5:161482015. View Article : Google Scholar : PubMed/NCBI

73 

Gao J, Xu K, Liu H, Liu G, Bai M, Peng C, Li T and Yin Y: Impact of the gut microbiota on intestinal immunity mediated by tryptophan metabolism. Front Cell Infect Microbiol. 8:132018. View Article : Google Scholar : PubMed/NCBI

74 

Szelest M, Walczak K and Plech T: A new insight into the potential role of tryptophan-derived AhR ligands in skin physiological and pathological processes. Int J Mol Sci. 22:11042021. View Article : Google Scholar : PubMed/NCBI

75 

Sun M, Ma N, He T, Johnston LJ and Ma X: Tryptophan (Trp) modulates gut homeostasis via aryl hydrocarbon receptor (AhR). Crit Rev Food Sci Nutr. 60:1760–1768. 2020. View Article : Google Scholar

76 

Nicolas GR and Chang PV: Deciphering the chemical lexicon of host-gut microbiota interactions. Trends Pharmacol Sci. 40:430–445. 2019. View Article : Google Scholar : PubMed/NCBI

77 

Xie L, Wu Q, Li K, Khan MAS, Zhang A, Sinha B, Li S, Chang SL, Brody DL, Grinstaff MW, et al: Tryptophan metabolism in Alzheimer's disease with the involvement of microglia and astrocyte crosstalk and gut-brain axis. Aging Dis. 15:2168–2190. 2024. View Article : Google Scholar : PubMed/NCBI

78 

Rothhammer V, Borucki DM, Tjon EC, Takenaka MC, Chao CC, Ardura-Fabregat A, de Lima KA, Gutiérrez-Vázquez C, Hewson P, Staszewski O, et al: Microglial control of astrocytes in response to microbial metabolites. Nature. 557:724–728. 2018. View Article : Google Scholar : PubMed/NCBI

79 

Rothhammer V, Mascanfroni ID, Bunse L, Takenaka MC, Kenison JE, Mayo L, Chao CC, Patel B, Yan R, Blain M, et al: Type I interferons and microbial metabolites of tryptophan modulate astrocyte activity and central nervous system inflammation via the aryl hydrocarbon receptor. Nat Med. 22:586–597. 2016. View Article : Google Scholar : PubMed/NCBI

80 

Marsland BJ: Regulating inflammation with microbial metabolites. Nat Med. 22:581–583. 2016. View Article : Google Scholar : PubMed/NCBI

81 

Wang P, Sun H, Maitiabula G, Zhang L, Yang J, Zhang Y, Gao X, Li J, Xue B, Li CJ and Wang X: Total parenteral nutrition impairs glucose metabolism by modifying the gut microbiome. Nat Metab. 5:331–348. 2023. View Article : Google Scholar : PubMed/NCBI

82 

Chimerel C, Emery E, Summers DK, Keyser U, Gribble FM and Reimann F: Bacterial metabolite indole modulates incretin secretion from intestinal enteroendocrine L cells. Cell Rep. 9:1202–1208. 2014. View Article : Google Scholar : PubMed/NCBI

83 

Taati M, Barzegar PEF and Raisi A: Exercise improves spatial learning and memory performance through the central GLP-1 receptors. Behav Neurol. 2022:29006282022. View Article : Google Scholar : PubMed/NCBI

84 

Budni J, Bellettini-Santos T, Mina F, Garcez ML and Zugno AI: The involvement of BDNF, NGF and GDNF in aging and Alzheimer's disease. Aging Dis. 6:331–341. 2015. View Article : Google Scholar : PubMed/NCBI

85 

Athauda D and Foltynie T: Protective effects of the GLP-1 mimetic exendin-4 in Parkinson's disease. Neuropharmacology. 136:260–270. 2018. View Article : Google Scholar

86 

van Bloemendaal L, Ten Kulve JS, la Fleur SE, Ijzerman RG and Diamant M: Effects of glucagon-like peptide 1 on appetite and body weight: focus on the CNS. J Endocrinol. 221:T1–T16. 2014. View Article : Google Scholar

87 

Mir FA and Jha SK: The Kir channel in the nucleus tractus solitarius integrates the chemosensory system with REM sleep executive machinery for homeostatic balance. Sci Rep. 14:216512024. View Article : Google Scholar : PubMed/NCBI

88 

Zheng D, Ratiner K and Elinav E: Circadian influences of diet on the microbiome and immunity. Trends Immunol. 41:512–530. 2020. View Article : Google Scholar : PubMed/NCBI

89 

Kuang Z, Wang Y, Li Y, Ye C, Ruhn KA, Behrendt CL, Olson EN and Hooper LV: The intestinal microbiota programs diurnal rhythms in host metabolism through histone deacetylase 3. Science. 365:1428–1434. 2019. View Article : Google Scholar : PubMed/NCBI

90 

Ni Y, Ma L, Wu T, Lim AL, Zhang W, Yang L, Nakao Y and Fu Z: The involvement of sympathetic nervous system in essence of chicken-facilitated physiological adaption and circadian resetting. Life Sci. 201:54–62. 2018. View Article : Google Scholar : PubMed/NCBI

91 

Nobs SP, Tuganbaev T and Elinav E: Microbiome diurnal rhythmicity and its impact on host physiology and disease risk. EMBO Rep. 20:e471292019. View Article : Google Scholar : PubMed/NCBI

92 

Thaiss CA, Levy M, Korem T, Dohnalová L, Shapiro H, Jaitin DA, David E, Winter DR, Gury-BenAri M, Tatirovsky E, et al: Microbiota diurnal rhythmicity programs host transcriptome oscillations. Cell. 167:1495–1510.e12. 2016. View Article : Google Scholar : PubMed/NCBI

93 

Zhang Y, Li Y, Yuan Y, Wang J, Zhang S, Zhu R, Wang Y, Wu Y, Liao X and Mi J: Reducing light exposure enhances the circadian rhythm of the biological clock through interactions with the gut microbiota. Sci Total Environ. 858:1600412023. View Article : Google Scholar

94 

Singh K, Jha NK and Thakur A: Spatiotemporal chromatin dynamics-A telltale of circadian epigenetic gene regulation. Life Sci. 221:377–391. 2019. View Article : Google Scholar : PubMed/NCBI

95 

Xiong L, Zhou W and Mas P: Illuminating the Arabidopsis circadian epigenome: Dynamics of histone acetylation and deacetylation. Curr Opin Plant Biol. 69:1022682022. View Article : Google Scholar : PubMed/NCBI

96 

Tahara Y, Yamazaki M, Sukigara H, Motohashi H, Sasaki H, Miyakawa H, Haraguchi A, Ikeda Y, Fukuda S and Shibata S: Gut microbiota-derived short chain fatty acids induce circadian clock entrainment in mouse peripheral tissue. Sci Rep. 8:13952018. View Article : Google Scholar : PubMed/NCBI

97 

Fawad JA, Luzader DH, Hanson GF, Moutinho TJ Jr, McKinney CA, Mitchell PG, Brown-Steinke K, Kumar A, Park M, Lee S, et al: Histone deacetylase inhibition by gut microbe-generated short-chain fatty acids entrains intestinal epithelial circadian rhythms. Gastroenterology. 163:1377–1390.e11. 2022. View Article : Google Scholar : PubMed/NCBI

98 

Kim DS, Woo JS, Min HK, Choi JW, Moon JH, Park MJ, Kwok SK, Park SH and Cho ML: Short-chain fatty acid butyrate induces IL-10-producing B cells by regulating circadian-clock-related genes to ameliorate Sjögren's syndrome. J Autoimmun. 119:1026112021. View Article : Google Scholar

99 

Jin UH, Lee SO, Sridharan G, Lee K, Davidson LA, Jayaraman A, Chapkin RS, Alaniz R and Safe S: Microbiome-derived tryptophan metabolites and their aryl hydrocarbon receptor-dependent agonist and antagonist activities. Mol Pharmacol. 85:777–788. 2014. View Article : Google Scholar : PubMed/NCBI

100 

Tischkau SA: Mechanisms of circadian clock interactions with aryl hydrocarbon receptor signalling. Eur J of Neurosci. 51:379–395. 2020. View Article : Google Scholar

101 

Salminen A: Aryl hydrocarbon receptor (AhR) impairs circadian regulation: Impact on the aging process. Ageing Res Rev. 87:1019282023. View Article : Google Scholar : PubMed/NCBI

102 

Petrus P, Cervantes M, Samad M, Sato T, Chao A, Sato S, Koronowski KB, Park G, Alam Y, Mejhert N, et al: Tryptophan metabolism is a physiological integrator regulating circadian rhythms. Mol Metab. 64:1015562022. View Article : Google Scholar : PubMed/NCBI

103 

Axelrod S, Li X, Sun Y, Lincoln S, Terceros A, O'Neil J, Wang Z, Nguyen A, Vora A, Spicer C, et al: The Drosophila blood-brain barrier regulates sleep via Moody G protein-coupled receptor signaling. Proc Natl Acad Sci USA. 120:e23093311202023. View Article : Google Scholar : PubMed/NCBI

104 

Pardridge WM and Fierer G: Transport of tryptophan into brain from the circulating, albumin-bound pool in rats and in rabbits. J Neurochem. 54:971–976. 1990. View Article : Google Scholar : PubMed/NCBI

105 

Sun N, Hu H, Wang F, Li L, Zhu W, Shen Y, Xiu J and Xu Q: Antibiotic-induced microbiome depletion in adult mice disrupts blood-brain barrier and facilitates brain infiltration of monocytes after bone-marrow transplantation. Brain Behav Immun. 92:102–114. 2021. View Article : Google Scholar

106 

Fröhlich EE, Farzi A, Mayerhofer R, Reichmann F, Jačan A, Wagner B, Zinser E, Bordag N, Magnes C, Fröhlich E, et al: Cognitive impairment by antibiotic-induced gut dysbiosis: Analysis of gut microbiota-brain communication. Brain Behav Immun. 56:1402016. View Article : Google Scholar : PubMed/NCBI

107 

Wen J, Ding Y, Wang L and Xiao Y: Gut microbiome improves postoperative cognitive function by decreasing permeability of the blood-brain barrier in aged mice. Brain Res Bull. 164:249–256. 2020. View Article : Google Scholar : PubMed/NCBI

108 

Praveenraj SS, Sonali S, Anand N, Tousif HA, Vichitra C, Kalyan M, Kanna PV, Chandana KA, Shasthara P, Mahalakshmi AM, et al: The role of a gut microbial-derived metabolite, trimethylamine N-oxide (TMAO), in neurological disorders. Mol Neurobiol. 59:6684–6700. 2022. View Article : Google Scholar : PubMed/NCBI

109 

Wallace TC, Blusztajn JK, Caudill MA, Klatt KC, Natker E, Zeisel SH and Zelman KM: Choline: The underconsumed and underappreciated essential nutrient. Nutr Today. 53:240–253. 2018. View Article : Google Scholar

110 

Janeiro MH, Ramírez MJ, Milagro FI, Martínez JA and Solas M: Implication of trimethylamine N-Oxide (TMAO) in disease: Potential biomarker or new therapeutic target. Nutrients. 10:13982018. View Article : Google Scholar : PubMed/NCBI

111 

Hoyles L, Pontifex MG, Rodriguez-Ramiro I, Anis-Alavi MA, Jelane KS, Snelling T, Solito E, Fonseca S, Carvalho AL, Carding SR, et al: Regulation of blood-brain barrier integrity by microbiome-associated methylamines and cognition by trimethylamine N-oxide. Microbiome. 9:2352021. View Article : Google Scholar : PubMed/NCBI

112 

Badran M, Khalyfa A, Ericsson AC, Puech C, McAdams Z, Bender SB and Gozal D: Gut microbiota mediate vascular dysfunction in a murine model of sleep apnoea: Effect of probiotics. Eur Respir J. 61:22000022023. View Article : Google Scholar

113 

Gamage AM, Liao C, Cheah IK, Chen Y, Lim DRX, Ku JWK, Chee RSL, Seebeck MGFP, Halliwell B and Gan YH: The proteobacterial species Burkholderia pseudomallei produces ergothioneine, which enhances virulence in mammalian infection. FASEB J. 32:6395–6409. 2018. View Article : Google Scholar

114 

Kalaras MD, Richie JP, Calcagnotto A and Beelman RB: Mushrooms: A rich source of the antioxidants ergothioneine and glutathione. Food Chem. 233:429–433. 2017. View Article : Google Scholar : PubMed/NCBI

115 

Vallianatou T, Lin W, Bèchet NB, Correia MS, Shanbhag NC, Lundgaard I and Globisch D: Differential regulation of oxidative stress, microbiota-derived, and energy metabolites in the mouse brain during sleep. J Cereb Blood Flow Metab. 41:3324–3338. 2021. View Article : Google Scholar : PubMed/NCBI

116 

Cheah IK and Halliwell B: Ergothioneine, recent developments. Redox Biol. 42:1018682021. View Article : Google Scholar : PubMed/NCBI

117 

Matsuda Y, Ozawa N, Shinozaki T, Wakabayashi KI, Suzuki K, Kawano Y, Ohtsu I and Tatebayashi Y: Ergothioneine, a metabolite of the gut bacterium Lactobacillus reuteri, protects against stress-induced sleep disturbances. Transl Psychiatry. 10:1702020. View Article : Google Scholar : PubMed/NCBI

118 

Buret AG, Allain T, Motta JP and Wallace JL: Effects of hydrogen sulfide on the microbiome: From toxicity to therapy. Antioxid Redox Signal. 36:211–219. 2022. View Article : Google Scholar :

119 

Tudor JC, Davis EJ, Peixoto L, Wimmer ME, van Tilborg E, Park AJ, Poplawski SG, Chung CW, Havekes R, Huang J, et al: Sleep deprivation impairs memory by attenuating mTORC1-dependent protein synthesis. Sci Signal. 9:ra412016. View Article : Google Scholar : PubMed/NCBI

120 

Wei HJ, Xu JH, Li MH, Tang JP, Zou W, Zhang P, Wang L, Wang CY and Tang XQ: Hydrogen sulfide inhibits homocysteine-induced endoplasmic reticulum stress and neuronal apoptosis in rat hippocampus via upregulation of the BDNF-TrkB pathway. Acta Pharmacol Sin. 35:707–715. 2014. View Article : Google Scholar : PubMed/NCBI

121 

Kang X, Jiang L, Lan F, Tang YY, Zhang P, Zou W, Chen YJ and Tang XQ: Hydrogen sulfide antagonizes sleep deprivation-induced depression- and anxiety-like behaviors by inhibiting neuroinflammation in a hippocampal Sirt1-dependent manner. Brain Res Bull. 177:194–202. 2021. View Article : Google Scholar : PubMed/NCBI

122 

Caspani G and Swann J: Small talk: Microbial metabolites involved in the signaling from microbiota to brain. Curr Opinion Pharmacol. 48:99–106. 2019. View Article : Google Scholar

123 

Bowers SJ, Vargas F, González A, He S, Jiang P, Dorrestein PC, Knight R, Wright KP Jr, Lowry CA, Fleshner M, et al: Repeated sleep disruption in mice leads to persistent shifts in the fecal microbiome and metabolome. PLoS One. 15:e02290012020. View Article : Google Scholar : PubMed/NCBI

124 

Fang D, Xu T, Sun J, Shi J, Li F, Yin Y, Wang Z and Liu Y: Nicotinamide mononucleotide ameliorates sleep deprivation-induced gut microbiota dysbiosis and restores colonization resistance against intestinal infections. Adv Sci (Weinh). 10:22071702023. View Article : Google Scholar : PubMed/NCBI

125 

Zielinski MR, McKenna JT and McCarley RW: Functions and mechanisms of sleep. AIMS Neurosci. 3:67–104. 2016. View Article : Google Scholar : PubMed/NCBI

126 

Kalinchuk AV, McCarley RW, Porkka-Heiskanen T and Basheer R: The time course of adenosine, nitric oxide (NO) and inducible NO synthase changes in the brain with sleep loss and their role in the non-rapid eye movement sleep homeostatic cascade. J Neurochem. 116:260–272. 2011. View Article : Google Scholar

127 

Chen L, Majde JA and Krueger JM: Spontaneous sleep in mice with targeted disruptions of neuronal or inducible nitric oxide synthase genes. Brain Res. 973:214–222. 2003. View Article : Google Scholar : PubMed/NCBI

128 

Porkka-Heiskanen T, Strecker RE, Thakkar M, Bjørkum AA, Greene RW and McCarley RW: Adenosine: A mediator of the sleep-inducing effects of prolonged wakefulness. Science. 276:1265–1268. 1997. View Article : Google Scholar : PubMed/NCBI

129 

Marini S, Santangeli O, Saarelainen P, Middleton B, Chowdhury N, Skene DJ, Costa R, Porkka-Heiskanen T and Montagnese S: Abnormalities in the polysomnographic, adenosine and metabolic response to sleep deprivation in an animal model of hyperammonemia. Front Physiol. 8:6362017. View Article : Google Scholar : PubMed/NCBI

130 

Aburto MR and Cryan JF: Gastrointestinal and brain barriers: Unlocking gates of communication across the microbiota-gut-brain axis. Nat Rev Gastroenterol Hepatol. 21:222–247. 2024. View Article : Google Scholar : PubMed/NCBI

131 

Schroeder S, Hofer SJ, Zimmermann A, Pechlaner R, Dammbrueck C, Pendl T, Marcello GM, Pogatschnigg V, Bergmann M, Müller M, et al: Dietary spermidine improves cognitive function. Cell Rep. 35:1089852021. View Article : Google Scholar : PubMed/NCBI

132 

Bedont JL, Kolesnik A, Pivarshev P, Malik D, Hsu CT, Weljie A and Sehgal A: Chronic sleep loss sensitizes Drosophila melanogaster to nitrogen stress. Curr Biol. 33:1613–1623.e5. 2023. View Article : Google Scholar : PubMed/NCBI

133 

Ren H, Kong X, Zhang Y, Deng F, Li J, Zhao F, Li P, Pei K, Tan J, Cheng Y, et al: The therapeutic potential of Ziziphi Spinosae Semen and Polygalae Radix in insomnia management: Insights from gut microbiota and serum metabolomics techniques. J Ethnopharmacol. 330:1182552024. View Article : Google Scholar : PubMed/NCBI

134 

Sun Y, Chen S, Wei R, Xie X, Wang C, Fan S, Zhang X, Su J, Liu J, Jia W and Wang X: Metabolome and gut microbiota variation with long-term intake of Panax ginseng extracts on rats. Food Funct. 9:3547–3556. 2018. View Article : Google Scholar : PubMed/NCBI

135 

Qiao T, Wang Y, Liang K, Zheng B, Ma J, Li F, Liu C, Zhu M and Song M: Effects of the Radix Ginseng and Semen Ziziphi Spinosae drug pair on the GLU/GABA-GLN metabolic cycle and the intestinal microflora of insomniac rats based on the brain-gut axis. Front Pharmacol. 13:10945072022. View Article : Google Scholar

136 

Hao KX, Shen CY and Jiang JG: Sedative and hypnotic effects of Polygala tenuifolia willd. Saponins on insomnia mice and their targets. J Ethnopharmacol. 323:1176182024. View Article : Google Scholar

137 

Fasina OB, Wang J, Mo J, Osada H, Ohno H, Pan W, Xiang L and Qi J: Gastrodin from gastrodia elata enhances cognitive function and neuroprotection of AD mice via the regulation of gut microbiota composition and inhibition of neuron inflammation. Front Pharmacol. 13:8142712022. View Article : Google Scholar : PubMed/NCBI

138 

Liu B, Li F, Xu Y, Wu Q and Shi J: Gastrodin improves cognitive dysfunction in REM sleep-deprived rats by regulating TLR4/NF-κB and Wnt/β-catenin signaling pathways. Brain Sci. 13:1792023. View Article : Google Scholar

139 

Zhu C, Zhang Z, Wang S and Sun Z: Study on the mechanism of Gastrodiae Rhizoma, Lycii Fructus, and Ziziphi Spinosae Semen in sedation and tranquillising mind. Mol Divers. 28:3279–3294. 2024. View Article : Google Scholar

140 

Chang HH, Yi PL, Cheng CH, Lu CY, Hsiao YT, Tsai YF, Li CL and Chang FC: Biphasic effects of baicalin, an active constituent of Scutellaria baicalensis Georgi, in the spontaneous sleep-wake regulation. J Ethnopharmacol. 135:359–368. 2011. View Article : Google Scholar : PubMed/NCBI

141 

Wan S, Wang L, Hao Z, Zhu L, Mao X, Li H, Sun P, Yin W, Fan K, Zhang H, et al: Baicalin ameliorates the gut barrier function and intestinal microbiota of broiler chickens. Acta Biochim Biophys Sin (Shanghai). 56:634–644. 2024.PubMed/NCBI

142 

Yao C, Wang Z, Jiang H, Yan R, Huang Q, Wang Y, Xie H, Zou Y, Yu Y and Lv L: Ganoderma lucidum promotes sleep through a gut microbiota-dependent and serotonin-involved pathway in mice. Sci Rep. 11:136602021. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Cheng H, Yang W, Xu H, Zhu W, Gong A, Yang X, Li S and Xu H: Microbiota metabolites affect sleep as drivers of brain‑gut communication (Review). Int J Mol Med 56: 130, 2025.
APA
Cheng, H., Yang, W., Xu, H., Zhu, W., Gong, A., Yang, X. ... Xu, H. (2025). Microbiota metabolites affect sleep as drivers of brain‑gut communication (Review). International Journal of Molecular Medicine, 56, 130. https://doi.org/10.3892/ijmm.2025.5571
MLA
Cheng, H., Yang, W., Xu, H., Zhu, W., Gong, A., Yang, X., Li, S., Xu, H."Microbiota metabolites affect sleep as drivers of brain‑gut communication (Review)". International Journal of Molecular Medicine 56.3 (2025): 130.
Chicago
Cheng, H., Yang, W., Xu, H., Zhu, W., Gong, A., Yang, X., Li, S., Xu, H."Microbiota metabolites affect sleep as drivers of brain‑gut communication (Review)". International Journal of Molecular Medicine 56, no. 3 (2025): 130. https://doi.org/10.3892/ijmm.2025.5571
Copy and paste a formatted citation
x
Spandidos Publications style
Cheng H, Yang W, Xu H, Zhu W, Gong A, Yang X, Li S and Xu H: Microbiota metabolites affect sleep as drivers of brain‑gut communication (Review). Int J Mol Med 56: 130, 2025.
APA
Cheng, H., Yang, W., Xu, H., Zhu, W., Gong, A., Yang, X. ... Xu, H. (2025). Microbiota metabolites affect sleep as drivers of brain‑gut communication (Review). International Journal of Molecular Medicine, 56, 130. https://doi.org/10.3892/ijmm.2025.5571
MLA
Cheng, H., Yang, W., Xu, H., Zhu, W., Gong, A., Yang, X., Li, S., Xu, H."Microbiota metabolites affect sleep as drivers of brain‑gut communication (Review)". International Journal of Molecular Medicine 56.3 (2025): 130.
Chicago
Cheng, H., Yang, W., Xu, H., Zhu, W., Gong, A., Yang, X., Li, S., Xu, H."Microbiota metabolites affect sleep as drivers of brain‑gut communication (Review)". International Journal of Molecular Medicine 56, no. 3 (2025): 130. https://doi.org/10.3892/ijmm.2025.5571
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