Gut-bacteria derived membrane vesicles and host metabolic health: a narrative review

References

• Engin A. The definition and prevalence of obesity and metabolic syndrome. Obesity Lipotoxicity. Adv Exp Med Biol. 2017;960:1–22. doi:10.1007/978-3-319-48382-5_1.
   PubMed Web of Science ®Google Scholar
• Caballero B. Humans against obesity: who will win? Advances in nutrition. Adv Nutr. 2019;10(suppl_1):S4–S9. doi:10.1093/advances/nmy055.
   PubMedGoogle Scholar
• Solomon CG, Manson JE. Obesity and mortality: a review of the epidemiologic data. Am J Clin Nutr. 1997;66(4):1044S–1050S. doi:10.1093/ajcn/66.4.1044S.
   PubMedGoogle Scholar
• Cotillard A, Kennedy SP, Kong LC, Prifti E, Pons N, Le Chatelier E, Almeida M, Quinquis B, Levenez F, Galleron N. et al. Dietary intervention impact on gut microbial gene richness. Nature. 2013;500(7464):585–588. doi:10.1038/nature12480.
   PubMed Web of Science ®Google Scholar
• Boucher J, Kleinridders A, Kahn CR. Insulin receptor signaling in normal and insulin-resistant states. Cold Spring Harb Perspect Biol. 2014;6(1):a009191. doi:10.1101/cshperspect.a009191.
   PubMed Web of Science ®Google Scholar
• Boden G. Obesity and free fatty acids. Endocrinol Metab Clin North Am. 2008;37(3):635–646. doi:10.1016/j.ecl.2008.06.007.
   PubMed Web of Science ®Google Scholar
• Cuevas-Sierra A, Ramos-Lopez O, Riezu-Boj JI, Milagro FI, Martinez JA. Diet, gut microbiota, and obesity: links with host genetics and epigenetics and potential applications. Adv Nutr. 2019;10(suppl_1):S17–S30. doi:10.1093/advances/nmy078.
   PubMed Web of Science ®Google Scholar
• Sen T, Cawthon CR, Ihde BT, Hajnal A, DiLorenzo PM, Claire B, Czaja K. Diet-driven microbiota dysbiosis is associated with vagal remodeling and obesity. Physiology & Behavior. 2017;173:305–317. doi:10.1016/j.physbeh.2017.02.027.
   PubMed Web of Science ®Google Scholar
• Canfora EE, Jocken JW, Blaak EE. Short-chain fatty acids in control of body weight and insulin sensitivity. Nat Rev Endocrinol. 2015;11(10):577–591. doi:10.1038/nrendo.2015.128.
   PubMed Web of Science ®Google Scholar
• Díaz‐Garrido N, Badia J, Baldomà L. Microbiota‐derived extracellular vesicles in interkingdom communication in the gut. J Extracell Vesicles. 2021;10(13):e12161. doi:10.1002/jev2.12161.
   PubMed Web of Science ®Google Scholar
• Kameli N, Borman R, López-Iglesias C, Savelkoul P, Stassen FR. Characterization of feces-derived bacterial membrane vesicles and the impact of their origin on the inflammatory response. Front Cell Infect Microbiol. 2021;11:667987. doi:10.3389/fcimb.2021.667987.
   PubMed Web of Science ®Google Scholar
• Toyofuku M, Nomura N, Eberl L. Types and origins of bacterial membrane vesicles. Nat Rev Microbiol. 2019;17(1):13–24. doi:10.1038/s41579-018-0112-2.
   PubMed Web of Science ®Google Scholar
• Bitto NJ, Chapman R, Pidot S, Costin A, Lo C, Choi J, D’Cruze T, Reynolds EC, Dashper SG, Turnbull L. et al. Bacterial membrane vesicles transport their DNA cargo into host cells. Sci Rep. 2017;7(1):1–11. doi:10.1038/s41598-017-07288-4.
   PubMedGoogle Scholar
• Dauros-Singorenko P, Blenkiron C, Phillips A, Swift S. The functional RNA cargo of bacterial membrane vesicles. FEMS Microbiol Lett. 2018;365(5):fny023. doi:10.1093/femsle/fny023.
   Web of Science ®Google Scholar
• Haurat MF, Aduse-Opoku J, Rangarajan M, Dorobantu L, Gray MR, Curtis MA, Feldman MF. Selective sorting of cargo proteins into bacterial membrane vesicles. Journal Of Biological Chemistry. 2011;286(2):1269–1276. doi:10.1074/jbc.M110.185744.
   PubMed Web of Science ®Google Scholar
• Toyofuku M, Schild S, Kaparakis-Liaskos M, Eberl L. Composition and functions of bacterial membrane vesicles. Nat Rev Microbiol. 2023;21(7):1–16. doi:10.1038/s41579-023-00875-5.
   Web of Science ®Google Scholar
• Jones EJ, Booth C, Fonseca S, Parker A, Cross K, Miquel-Clopés A, Hautefort I, Mayer U, Wileman T, Stentz R. et al. The uptake, trafficking, and biodistribution of Bacteroides thetaiotaomicron generated outer membrane vesicles. Front Microbiol. 2020;11:57. doi:10.3389/fmicb.2020.00057.
   PubMed Web of Science ®Google Scholar
• Park J-Y, Choi J, Lee Y, Lee J-E, Lee E-H, Kwon H-J, Yang J, Jeong B-R, Kim Y-K, Han P-L. et al. Metagenome analysis of bodily microbiota in a mouse model of Alzheimer disease using bacteria-derived membrane vesicles in blood. Exp Neurobiol. 2017;26(6):369. doi:10.5607/en.2017.26.6.369.
   PubMed Web of Science ®Google Scholar
• Lee EY, Bang JY, Park GW, Choi DS, Kang JS, Kim HJ, Park K-S, Lee J-O, Kim Y-K, Kwon K-H. et al. Global proteomic profiling of native outer membrane vesicles derived from Escherichia coli. Proteomics. 2007;7(17):3143–3153. doi:10.1002/pmic.200700196.
   PubMed Web of Science ®Google Scholar
• O’donoghue EJ, Krachler AM. Mechanisms of outer membrane vesicle entry into host cells. Cell Microbiol. 2016;18(11):1508–1517. doi:10.1111/cmi.12655.
   PubMed Web of Science ®Google Scholar
• Zakharzhevskaya NB, Tsvetkov VB, Vanyushkina AA, Varizhuk AM, Rakitina DV, Podgorsky VV, Vishnyakov IE, Kharlampieva DD, Manuvera VA, Lisitsyn FV. et al. Interaction of Bacteroides fragilis toxin with outer membrane vesicles reveals new mechanism of its secretion and delivery. Front Cell Infect Microbiol. 2017;7:2. doi:10.3389/fcimb.2017.00002.
   PubMed Web of Science ®Google Scholar
• Bitto NJ, Kaparakis-Liaskos M. The therapeutic benefit of bacterial membrane vesicles. Int J Mol Sci. 2017;18(6):1287. doi:10.3390/ijms18061287.
   PubMed Web of Science ®Google Scholar
• Choi Y, Kwon Y, Kim D-K, Jeon J, Jang SC, Wang T, Ban M, Kim M-H, Jeon SG, Kim M-S. et al. Gut microbe-derived extracellular vesicles induce insulin resistance, thereby impairing glucose metabolism in skeletal muscle. Sci Rep. 2015;5(1):1–11. doi:10.1038/srep15878.
   Google Scholar
• Ashrafian F, Keshavarz Azizi Raftar S, Lari A, Shahryari A, Abdollahiyan S, Moradi HR, Masoumi M, Davari M, Khatami S, Omrani MD. et al. Extracellular vesicles and pasteurized cells derived from Akkermansia muciniphila protect against high-fat induced obesity in mice. Microb Cell Fact. 2021;20(1):1–17. doi:10.1186/s12934-021-01709-w.
   PubMed Web of Science ®Google Scholar
• Seyama M, Yoshida K, Yoshida K, Fujiwara N, Ono K, Eguchi T, Kawai H, Guo J, Weng Y, Haoze Y. et al. Outer membrane vesicles of Porphyromonas gingivalis attenuate insulin sensitivity by delivering gingipains to the liver. Biochim Biophys Acta - Mol Basis Dis. 2020;1866(6):165731. doi:10.1016/j.bbadis.2020.165731.
   PubMed Web of Science ®Google Scholar
• Kameli N, Becker HE, Welbers T, Jonkers DM, Penders J, Savelkoul P, Stassen FR. Metagenomic profiling of fecal-derived bacterial membrane vesicles in crohn’s disease patients. Cells. 2021;10(10):2795. doi:10.3390/cells10102795.
   PubMed Web of Science ®Google Scholar
• Deatherage BL, Lara JC, Bergsbaken T, Barrett SLR, Lara S, Cookson BT. Biogenesis of bacterial membrane vesicles. Mol Microbiol. 2009;72(6):1395–1407. doi:10.1111/j.1365-2958.2009.06731.x.
   PubMed Web of Science ®Google Scholar
• Volgers C, Savelkoul PH, Stassen FR. Gram-negative bacterial membrane vesicle release in response to the host-environment: different threats, same trick? Crit Rev Microbiol. 2018;44(3):258–273. doi:10.1080/1040841X.2017.1353949.
   PubMed Web of Science ®Google Scholar
• Schlatterer K, Beck C, Hanzelmann D, Lebtig M, Fehrenbacher B, Schaller M, Ebner P, Nega M, Otto M, Kretschmer D. et al. The mechanism behind bacterial lipoprotein release: phenol-soluble modulins mediate Toll-like receptor 2 activation via extracellular vesicle release from Staphylococcus aureus. MBio. 2018;9(6):e01851–18. doi:10.1128/mBio.01851-18.
   PubMed Web of Science ®Google Scholar
• Palacios A, Gupta S, Rodriguez GM, Prados-Rosales R. Extracellular vesicles in the context of Mycobacterium tuberculosis infection. Mol Immunol. 2021;133:175–181. doi:10.1016/j.molimm.2021.02.010.
   PubMed Web of Science ®Google Scholar
• Hendrix A, De Wever O. Systemically circulating bacterial extracellular vesicles: Origin, fate, and function. Trends Microbiol. 2022;30(3):213–216. doi:10.1016/j.tim.2021.12.012.
   PubMed Web of Science ®Google Scholar
• Yasuda M, Yamamoto T, Nagakubo T, Morinaga K, Obana N, Nomura N, Toyofuku M. Phage genes induce quorum sensing signal release through membrane vesicle formation. Microb Environ. 2022;37(1):ME21067. doi:10.1264/jsme2.ME21067.
   PubMed Web of Science ®Google Scholar
• Mandal PK, Ballerin G, Nolan LM, Petty NK, Whitchurch CB. Bacteriophage infection of Escherichia coli leads to the formation of membrane vesicles via both explosive cell lysis and membrane blebbing. Microbiology. 2021;167(4). doi:10.1099/mic.0.001021.
   PubMed Web of Science ®Google Scholar
• Tan J, Ni D, Taitz J, Pinget GV, Read M, Senior A, Wali JA, Elnour R, Shanahan E, Wu H. et al. Dietary protein increases T-cell-independent sIgA production through changes in gut microbiota-derived extracellular vesicles. Nat Commun. 2022;13(1):4336. doi:10.1038/s41467-022-31761-y.
   PubMed Web of Science ®Google Scholar
• Lagos L, Leanti La Rosa SØ, Arntzen M, Ånestad R, Terrapon N, Gaby JC, Westereng B. Isolation and characterization of extracellular vesicles secreted in vitro by porcine microbiota. Microorganisms. 2020;8(7):983. doi:10.3390/microorganisms8070983.
   PubMed Web of Science ®Google Scholar
• Erlandson KM, Liu J, Johnson R, Dillon S, Jankowski CM, Kroehl M, Robertson CE, Frank DN, Tuncil Y, Higgins J. et al. An exercise intervention alters stool microbiota and metabolites among older, sedentary adults. Ther Adv Infect Dis. 2021;8:20499361211027067. doi:10.1177/20499361211027067.
   Web of Science ®Google Scholar
• Zhong X, Powell C, Phillips CM, Millar S, Carson BP, Dowd KP, Perry IJ, Kearney PM, Harrington JM, O’Toole PW. et al. The influence of different physical activity behaviours on the gut microbiota of older Irish adults. J Nutr Health Aging. 2021;25(7):854–861. doi:10.1007/s12603-021-1630-6.
   PubMed Web of Science ®Google Scholar
• Andreoni F, Toyofuku M, Menzi C, Kalawong R, Mairpady Shambat S, François P, Zinkernagel AS, Eberl L. Antibiotics stimulate formation of vesicles in staphylococcus aureus in both phage-dependent and -independent fashions and via different routes. Antimicrob Agents Chemother. 2019;63(2):e01439–18. doi:10.1128/AAC.01439-18.
   PubMed Web of Science ®Google Scholar
• Kadurugamuwa J, Beveridge T. Natural release of virulence factors in membrane vesicles by Pseudomonas aeruginosa and the effect of aminoglycoside antibiotics on their release. J Antimicrob Chemother. 1997;40(5):615–621. doi:10.1093/jac/40.5.615.
   PubMed Web of Science ®Google Scholar
• Juodeikis R, Martins C, Saalbach G, Richardson J, Koev T, Baker DJ, Defernez M, Warren M, Carding SR. Differential temporal release and lipoprotein loading in B. thetaiotaomicron bacterial extracellular vesicles. J Of Extracellular Vesicle. 2024;13(1):12406. doi:10.1002/jev2.12406.
   PubMed Web of Science ®Google Scholar
• Turnbull L, Toyofuku M, Hynen AL, Kurosawa M, Pessi G, Petty NK, Osvath SR, Cárcamo-Oyarce G, Gloag ES, Shimoni R. et al. Explosive cell lysis as a mechanism for the biogenesis of bacterial membrane vesicles and biofilms. Nat Commun. 2016;7(1):11220. doi:10.1038/ncomms11220.
   PubMedGoogle Scholar
• Zingl FG, Kohl P, Cakar F, Leitner DR, Mitterer F, Bonnington KE, Rechberger GN, Kuehn MJ, Guan Z, Reidl J. et al. Outer membrane vesiculation facilitates surface exchange and in vivo adaptation of Vibrio cholerae. Cell Host Microbe. 2020;27(2):225–37. e8. doi:10.1016/j.chom.2019.12.002.
   PubMed Web of Science ®Google Scholar
• van de Waterbeemd B, Zomer G, van den IJssel J, van Keulen L, Eppink MH, van der Ley P, van der Pol LA. Cysteine depletion causes oxidative stress and triggers outer membrane vesicle release by Neisseria meningitidis; implications for vaccine development. PLOS ONE. 2013;8(1):e54314. doi:10.1371/journal.pone.0054314.
   PubMed Web of Science ®Google Scholar
• Marotti I, Bregola V, Aloisio I, Di Gioia D, Bosi S, Di Silvestro R, Quinn R, Dinelli G. Prebiotic effect of soluble fibres from modern and old durum‐type wheat varieties on Lactobacillus and Bifidobacterium strains. J Sci Food Agric. 2012;92(10):2133–2140. doi:10.1002/jsfa.5597.
   PubMed Web of Science ®Google Scholar
• Tomova A, Bukovsky I, Rembert E, Yonas W, Alwarith J, Barnard ND, Kahleova H. The effects of vegetarian and vegan diets on gut microbiota. Front Nutr. 2019;6:47. doi:10.3389/fnut.2019.00047.
   PubMed Web of Science ®Google Scholar
• Thomson C, Garcia AL, Edwards CA. Interactions between dietary fibre and the gut microbiota. Proc Nutr Soc. 2021;80(4):398–408. doi:10.1017/S0029665121002834.
   Web of Science ®Google Scholar
• Müller L, Kuhn T, Koch M, Fuhrmann G. Stimulation of probiotic bacteria induces release of membrane vesicles with augmented anti-inflammatory activity. ACS Appl Bio Mater. 2021;4(5):3739–3748. doi:10.1021/acsabm.0c01136.
   PubMedGoogle Scholar
• Farmer AD, Mohammed SD, Dukes GE, Scott SM, Hobson AR. Caecal pH is a biomarker of excessive colonic fermentation. World J Gastroenterol: WJG. 2014;20(17):5000. doi:10.3748/wjg.v20.i17.5000.
   PubMed Web of Science ®Google Scholar
• Duncan SH, Louis P, Thomson JM, Flint HJ. The role of pH in determining the species composition of the human colonic microbiota. Environ Microbiol. 2009;11(8):2112–2122. doi:10.1111/j.1462-2920.2009.01931.x.
   PubMed Web of Science ®Google Scholar
• Luo Z, Ji Y, Gao H, Dos Reis FCG, Bandyopadhyay G, Jin Z, Ly C, Chang Y-J, Zhang D, Kumar D. et al. CRIg+ macrophages prevent gut microbial DNA–containing extracellular vesicle–induced tissue inflammation and insulin resistance. Gastroenterology. 2021;160(3):863–874. doi:10.1053/j.gastro.2020.10.042.
   PubMed Web of Science ®Google Scholar
• Bitto NJ, Zavan L, Johnston EL, Stinear TP, Hill AF, Kaparakis-Liaskos M, Edelmann MJ. Considerations for the analysis of bacterial membrane vesicles: methods of vesicle production and quantification can influence biological and experimental outcomes. Microbiol Spectr. 2021;9(3):e01273–21. doi:10.1128/Spectrum.01273-21.
   PubMed Web of Science ®Google Scholar
• Li C-C, Hsu W-F, Chiang P-C, Kuo M-C, Wo AM, Tseng YJ. Characterization of markers, functional properties, and microbiome composition in human gut-derived bacterial extracellular vesicles. Gut Microbes. 2023;15(2):2288200. doi:10.1080/19490976.2023.2288200.
   PubMedGoogle Scholar
• Xiu L, Wu Y, Lin G, Zhang Y, Huang L. Bacterial membrane vesicles: orchestrators of interkingdom interactions in microbial communities for environmental adaptation and pathogenic dynamics. Front Immunol. 2024;15:1371317. doi:10.3389/fimmu.2024.1371317.
   PubMed Web of Science ®Google Scholar
• Faddetta T, Renzone G, Vassallo A, Rimini E, Nasillo G, Buscarino G, Agnello S, Licciardi M, Botta L, Scaloni A. et al. Streptomyces coelicolor vesicles: many molecules to be delivered. Appl Environ Microb. 2022;88(1):e01881–21. doi:10.1128/AEM.01881-21.
   PubMed Web of Science ®Google Scholar
• Elhenawy W, Debelyy MO, Feldman MF, Whiteley M, Greenberg EP. Preferential packing of acidic glycosidases and proteases into Bacteroides outer membrane vesicles. MBio. 2014;5(2):e00909–14. doi:10.1128/mBio.00909-14.
   PubMed Web of Science ®Google Scholar
• Evans AG, Davey HM, Cookson A, Currinn H, Cooke-Fox G, Stanczyk PJ, Whitworth DE. Predatory activity of Myxococcus xanthus outer-membrane vesicles and properties of their hydrolase cargo. Microbiology. 2012;158(11):2742–2752. doi:10.1099/mic.0.060343-0.
   PubMedGoogle Scholar
• Chelakkot C, Choi Y, Kim D-K, Park HT, Ghim J, Kwon Y, Jeon J, Kim M-S, Jee Y-K, Gho YS. et al. Akkermansia muciniphila-derived extracellular vesicles influence gut permeability through the regulation of tight junctions. Experimental & Molecular Medicine. 2018;50(2):e450–e. doi:10.1038/emm.2017.282.
   PubMed Web of Science ®Google Scholar
• Shen Y, Torchia MLG, Lawson GW, Karp CL, Ashwell JD, Mazmanian SK. Outer membrane vesicles of a human commensal mediate immune regulation and disease protection. Cell Host Microbe. 2012;12(4):509–520. doi:10.1016/j.chom.2012.08.004.
   PubMed Web of Science ®Google Scholar
• Chu H, Khosravi A, Kusumawardhani IP, Kwon AH, Vasconcelos AC, Cunha LD, Mayer AE, Shen Y, Wu W-L, Kambal A. et al. Gene-microbiota interactions contribute to the pathogenesis of inflammatory bowel disease. Science. 2016;352(6289):1116–1120. doi:10.1126/science.aad9948.
   PubMed Web of Science ®Google Scholar
• Shi J, Ma D, Gao S, Long F, Wang X, Pu X, Cannon RD, Han T-L. Probiotic Escherichia coli Nissle 1917-derived outer membrane vesicles modulate the intestinal microbiome and host gut-liver metabolome in obese and diabetic mice. Front Microbiol. 2023;14:14. doi:10.3389/fmicb.2023.1219763.
   Web of Science ®Google Scholar
• Fábrega MJ, Aguilera L, Gimenez R, Varela E, Alexandra CañCañAs M, Antolín M, Badía J, Baldomà L. Activation of immune and defense responses in the intestinal mucosa by outer membrane vesicles of commensal and probiotic Escherichia coli strains. Front Microbiol. 2016;7:705. doi:10.3389/fmicb.2016.00705.
   PubMed Web of Science ®Google Scholar
• Alvarez C-S, Badia J, Bosch M, Giménez R, Baldomà L. Outer membrane vesicles and soluble factors released by probiotic Escherichia coli Nissle 1917 and commensal ECOR63 enhance barrier function by regulating expression of tight junction proteins in intestinal epithelial cells. Front Microbiol. 2016;7:1981. doi:10.3389/fmicb.2016.01981.
   PubMed Web of Science ®Google Scholar
• Alvarez C-S, Giménez R, CañCañAs M-A, Vera R, Díaz-Garrido N, Badia J, Baldomà L. Extracellular vesicles and soluble factors secreted by Escherichia coli Nissle 1917 and ECOR63 protect against enteropathogenic E. coli-induced intestinal epithelial barrier dysfunction. BMC Microbiol. 2019;19(1):1–12. doi:10.1186/s12866-019-1534-3.
   PubMedGoogle Scholar
• Fleetwood AJ, Lee MK, Singleton W, Achuthan A, Lee M-C, O’Brien-Simpson NM, Cook AD, Murphy AJ, Dashper SG, Reynolds EC. et al. Metabolic remodeling, inflammasome activation, and pyroptosis in macrophages stimulated by Porphyromonas gingivalis and its outer membrane vesicles. Front Cell Infect Microbiol. 2017;7:351. doi:10.3389/fcimb.2017.00351.
   PubMed Web of Science ®Google Scholar
• Ghaderi F, Sotoodehnejadnematalahi F, Hajebrahimi Z, Fateh A, Siadat SD. Effects of active, inactive, and derivatives of Akkermansia muciniphila on the expression of the endocannabinoid system and PPARs genes. Sci Rep. 2022;12(1):10031. doi:10.1038/s41598-022-13840-8.
   PubMed Web of Science ®Google Scholar
• Bittel M, Reichert P, Sarfati I, Dressel A, Leikam S, Uderhardt S, Stolzer I, Phu TA, Ng M, Vu NK. et al. Visualizing transfer of microbial biomolecules by outer membrane vesicles in microbe‐host‐communication in vivo. J Extracell Vesicles. 2021;10(12):e12159. doi:10.1002/jev2.12159.
   PubMed Web of Science ®Google Scholar
• Turunen J, Tejesvi MV, Suokas M, Virtanen N, Paalanne N, Kaisanlahti A, Reunanen J, Tapiainen T. Bacterial extracellular vesicles in the microbiome of first-pass meconium in newborn infants. Pediatr Res. 2023;93(4):887–896. doi:10.1038/s41390-022-02242-1.
   PubMed Web of Science ®Google Scholar
• Nikkari S, McLaughlin IJ, Bi W, Dodge DE, Relman DA. Does blood of healthy subjects contain bacterial ribosomal DNA? J Clin Microbiol. 2001;39(5):1956–1959.
   PubMed Web of Science ®Google Scholar
• Païssé S, Valle C, Servant F, Courtney M, Burcelin R, Amar J, Lelouvier B. Comprehensive description of blood microbiome from healthy donors assessed by 16 S targeted metagenomic sequencing. Transfusion. 2016;56(5):1138–1147. doi:10.1111/trf.13477.
   PubMed Web of Science ®Google Scholar
• Massier L, Chakaroun R, Tabei S, Crane A, Didt KD, Fallmann J, von Bergen M, Haange S-B, Heyne H, Stumvoll M. et al. Adipose tissue derived bacteria are associated with inflammation in obesity and type 2 diabetes. Gut. 2020;69(10):1796–1806. doi:10.1136/gutjnl-2019-320118.
   PubMed Web of Science ®Google Scholar
• Gosiewski T, Ludwig-Galezowska A, Huminska K, Sroka-Oleksiak A, Radkowski P, Salamon D, Wojciechowicz J, Kus-Slowinska M, Bulanda M, Wolkow PP. et al. Comprehensive detection and identification of bacterial DNA in the blood of patients with sepsis and healthy volunteers using next-generation sequencing method-the observation of DNAemia. Eur J Clin Microbiol Infect Dis. 2017;36(2):329–336. doi:10.1007/s10096-016-2805-7.
   PubMed Web of Science ®Google Scholar
• Chakaroun RM, Massier L, Kovacs P. Gut microbiome, intestinal permeability, and tissue bacteria in metabolic disease: perpetrators or bystanders? Nutrients. 2020;12(4):1082. doi:10.3390/nu12041082.
   PubMed Web of Science ®Google Scholar
• Balmer ML, Slack E, De Gottardi A, Lawson MA, Hapfelmeier S, Miele L, Grieco A, Van Vlierberghe H, Fahrner R, Patuto N. et al. The liver may act as a firewall mediating mutualism between the host and its gut commensal microbiota. Sci Transl Med. 2014;6(237):ra23766–ra66. doi:10.1126/scitranslmed.3008618.
   Web of Science ®Google Scholar
• Villarroel J, Donkin I, Champion C, Burcelin R, Barrès R. Endurance training in humans modulates the bacterial DNA signature of skeletal muscle. Biomedicines. 2021;10(1):64. doi:10.3390/biomedicines10010064.
   PubMed Web of Science ®Google Scholar
• Pietrzak B, Kawacka I, Olejnik-Schmidt A, Schmidt M. Circulating microbial cell-free DNA in health and disease. Int J Mol Sci. 2023;24(3):3051. doi:10.3390/ijms24033051.
   PubMed Web of Science ®Google Scholar
• Han DS, Lo YD. The nexus of cfDNA and nuclease biology. Trends Genet. 2021;37(8):758–770. doi:10.1016/j.tig.2021.04.005.
   PubMed Web of Science ®Google Scholar
• Thaiss CA, Levy M, Grosheva I, Zheng D, Soffer E, Blacher E, Braverman S, Tengeler AC, Barak O, Elazar M. et al. Hyperglycemia drives intestinal barrier dysfunction and risk for enteric infection. Science. 2018;359(6382):1376–1383. doi:10.1126/science.aar3318.
   PubMed Web of Science ®Google Scholar
• Chang J, Leong RW, Wasinger VC, Ip M, Yang M, Phan TG. Impaired intestinal permeability contributes to ongoing bowel symptoms in patients with inflammatory bowel disease and mucosal healing. Gastroenterology. 2017;153(3):723–31. e1. doi:10.1053/j.gastro.2017.05.056.
   PubMed Web of Science ®Google Scholar
• Epple H-J, Schneider T, Troeger H, Kunkel D, Allers K, Moos V, Amasheh M, Loddenkemper C, Fromm M, Zeitz M. et al. Impairment of the intestinal barrier is evident in untreated but absent in suppressively treated HIV-infected patients. Gut. 2009;58(2):220–227. doi:10.1136/gut.2008.150425.
   PubMed Web of Science ®Google Scholar
• Tran L, Greenwood-Van Meerveld B. Age-associated remodeling of the intestinal epithelial barrier. J Gerontol A Biol Sci Med Sci. 2013;68(9):1045–1056. doi:10.1093/gerona/glt106.
   PubMed Web of Science ®Google Scholar
• Tulkens J, Vergauwen G, Van Deun J, Geeurickx E, Dhondt B, Lippens L, De Scheerder M-A, Miinalainen I, Rappu P, De Geest BG. et al. Increased levels of systemic LPS-positive bacterial extracellular vesicles in patients with intestinal barrier dysfunction. Gut. 2020;69(1):191–193. doi:10.1136/gutjnl-2018-317726.
   PubMed Web of Science ®Google Scholar
• Parlesak A, Schäfer C, Schütz T, Bode JC, Bode C. Increased intestinal permeability to macromolecules and endotoxemia in patients with chronic alcohol abuse in different stages of alcohol-induced liver disease. J Hepatol. 2000;32(5):742–747. doi:10.1016/S0168-8278(00)80242-1.
   PubMed Web of Science ®Google Scholar
• Cheng WT, Kantilal HK, Davamani F. The mechanism of Bacteroides fragilis toxin contributes to colon cancer formation. Malaysian J Med Sci: MJMS. 2020;27(4):9. doi:10.21315/mjms2020.27.4.2.
   PubMed Web of Science ®Google Scholar
• Wick EC, Rabizadeh S, Albesiano E, Wu X, Wu S, Chan J, Rhee K-J, Ortega G, Huso DL, Pardoll D. et al. Stat3 activation in murine colitis induced by enterotoxigenic Bacteroides fragilis. Inflamm Bowel Dis. 2014;20(5):821–834. doi:10.1097/MIB.0000000000000019.
   PubMed Web of Science ®Google Scholar
• Tsuzuno T, Takahashi N, Yamada‐Hara M, Yokoji‐Takeuchi M, Sulijaya B, Aoki‐Nonaka Y, Matsugishi A, Katakura K, Tabeta K, Yamazaki K. et al. Ingestion of Porphyromonas gingivalis exacerbates colitis via intestinal epithelial barrier disruption in mice. J Periodontal Res. 2021;56(2):275–288. doi:10.1111/jre.12816.
   PubMed Web of Science ®Google Scholar
• Furuta N, Tsuda K, Omori H, Yoshimori T, Yoshimura F, Amano A. Porphyromonas gingivalis outer membrane vesicles enter human epithelial cells via an endocytic pathway and are sorted to lysosomal compartments. Infect Immun. 2009;77(10):4187–4196. doi:10.1128/IAI.00009-09.
   PubMed Web of Science ®Google Scholar
• Furuta N, Takeuchi H, Amano A. Entry of Porphyromonas gingivalis outer membrane vesicles into epithelial cells causes cellular functional impairment. Infect Immun. 2009;77(11):4761–4770. doi:10.1128/IAI.00841-09.
   PubMed Web of Science ®Google Scholar
• Apovian CM, Bigornia S, Mott M, Meyers MR, Ulloor J, Gagua M, McDonnell M, Hess D, Joseph L, Gokce N. et al. Adipose macrophage infiltration is associated with insulin resistance and vascular endothelial dysfunction in obese subjects. Arterioscler Thromb Vasc Biol. 2008;28(9):1654–1659. doi:10.1161/ATVBAHA.108.170316.
   PubMed Web of Science ®Google Scholar
• Lee K-E, Kim J-K, Han S-K, Lee DY, Lee H-J, Yim S-V, Kim D-H. The extracellular vesicle of gut microbial Paenalcaligenes hominis is a risk factor for vagus nerve-mediated cognitive impairment. Microbiome. 2020;8(1):1–18. doi:10.1186/s40168-020-00881-2.
   PubMed Web of Science ®Google Scholar
• Emery DC, Shoemark DK, Batstone TE, Waterfall CM, Coghill JA, Cerajewska TL, Davies M, West NX, Allen SJ. 16S rRNA next generation sequencing analysis shows bacteria in Alzheimer’s post-mortem brain. Front Aging Neurosci. 2017;9:195. doi:10.3389/fnagi.2017.00195.
   PubMed Web of Science ®Google Scholar
• Bell RD, Winkler EA, Singh I, Sagare AP, Deane R, Wu Z, Holtzman DM, Betsholtz C, Armulik A, Sallstrom J. et al. Apolipoprotein E controls cerebrovascular integrity via cyclophilin A. Nature. 2012;485(7399):512–516. doi:10.1038/nature11087.
   PubMed Web of Science ®Google Scholar
• Zhan X, Stamova B, Jin L-W, DeCarli C, Phinney B, Sharp FR. Gram-negative bacterial molecules associate with Alzheimer disease pathology. Neurology. 2016;87(22):2324–2332. doi:10.1212/WNL.0000000000003391.
   PubMed Web of Science ®Google Scholar
• Kim SY, Yi DY. Analysis of the human breast milk microbiome and bacterial extracellular vesicles in healthy mothers. Experimental & Molecular Medicine. 2020;52(8):1288–1297. doi:10.1038/s12276-020-0470-5.
   PubMed Web of Science ®Google Scholar
• Gao H, Luo Z, Ji Y, Tang K, Jin Z, Ly C, Sears DD, Mahata S, Ying W. Accumulation of microbial DNAs promotes to islet inflammation and β cell abnormalities in obesity in mice. Nat Commun. 2022;13(1):565. doi:10.1038/s41467-022-28239-2.
   PubMed Web of Science ®Google Scholar
• Erttmann SF, Swacha P, Aung KM, Brindefalk B, Jiang H, Härtlova A, Uhlin BE, Wai SN, Gekara NO. The gut microbiota prime systemic antiviral immunity via the cGAS-STING-IFN-I axis. Immunity. 2022;55(5):847–61. e10. doi:10.1016/j.immuni.2022.04.006.
   PubMed Web of Science ®Google Scholar
• Kredel LI, Batra A, Stroh T, Kühl AA, Zeitz M, Erben U. et al. Adipokines from local fat cells shape the macrophage compartment of the creeping fat in Crohn’s disease. Gut. 2013;62(6):852–862. doi:10.1136/gutjnl-2011-301424.
   PubMed Web of Science ®Google Scholar
• Bilski J, Mazur-Bialy A, Wojcik D, Surmiak M, Magierowski M, Sliwowski Z, Pajdo R, Kwiecien S, Danielak A, Ptak-Belowska A. et al. Role of obesity, mesenteric adipose tissue, and adipokines in inflammatory bowel diseases. Biomolecules. 2019;9(12):780. doi:10.3390/biom9120780.
   PubMed Web of Science ®Google Scholar
• Wu Z, Tan J, Chi Y, Zhang F, Xu J, Song Y, Cong X, Wu N, Liu Y. Mesenteric adipose tissue contributes to intestinal barrier integrity and protects against nonalcoholic fatty liver disease in mice. Am J Physiol-Gastr L. 2018;315(5):G659–G670. doi:10.1152/ajpgi.00079.2018.
   PubMed Web of Science ®Google Scholar
• Anhê FF, Jensen BAH, Varin TV, Servant F, Van Blerk S, Richard D, Marceau S, Surette M, Biertho L, Lelouvier B. et al. Type 2 diabetes influences bacterial tissue compartmentalisation in human obesity. Nat Metab. 2020;2(3):233–242. doi:10.1038/s42255-020-0178-9.
   PubMedGoogle Scholar
• Ali S, Malloci M, Safiedeen Z, Soleti R, Vergori L, Vidal-Gómez X, Besnard C, Dubois S, Le Lay S, Boursier J. et al. LPS-enriched small extracellular vesicles from metabolic syndrome patients trigger endothelial dysfunction by activation of TLR4. Metabolism. 2021;118:154727. doi:10.1016/j.metabol.2021.154727.
   PubMed Web of Science ®Google Scholar
• Prados-Rosales R, Baena A, Martinez LR, Luque-Garcia J, Kalscheuer R, Veeraraghavan U, Camara C, Nosanchuk JD, Besra GS, Chen B. et al. Mycobacteria release active membrane vesicles that modulate immune responses in a TLR2-dependent manner in mice. J Clin Invest. 2011;121(4):1471–1483. doi:10.1172/JCI44261.
   PubMed Web of Science ®Google Scholar
• Jin M, Lai Y, Zhao P, Shen Q, Su W, Yin Y, Zhang W. Effects of peptidoglycan on the development of steatohepatitis. Biochimica et Biophysica Acta (BBA) - Mol Cell Biol Lipids. 2020;1865(4):158595. doi:10.1016/j.bbalip.2019.158595.
   PubMed Web of Science ®Google Scholar
• Chen H, Sun L, Feng L, Mulholland M, Zhang W, Yin Y. Peptidoglycan inhibits beigeing of adipose tissue. Acta Pharm Sin B. 2022;12(2):990. doi:10.1016/j.apsb.2021.11.015.
   PubMed Web of Science ®Google Scholar
• Nonogaki K, Moser A, Pan X-M, Staprans I, Grunfeld C, Feingold K. Lipoteichoic acid stimulates lipolysis and hepatic triglyceride secretion in rats in vivo. J Lipid Res. 1995;36(9):1987–1995. doi:10.1016/S0022-2275(20)41116-2.
   PubMed Web of Science ®Google Scholar
• Galton DJ. The human adipose cell: a model for errors in metabolic regulation. London (UK): Butterworth & Co. Ltd.; 1971.
   Google Scholar
• Cani PD, Amar J, Iglesias MA, Poggi M, Knauf C, Bastelica D, Neyrinck AM, Fava F, Tuohy KM, Chabo C. et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes. 2007;56(7):1761–1772. doi:10.2337/db06-1491.
   PubMed Web of Science ®Google Scholar
• Bitto NJ, Cheng L, Johnston EL, Pathirana R, Phan TK, Poon IK, O’Brien‐Simpson NM, Hill AF, Stinear TP, Kaparakis‐Liaskos M. et al. Staphylococcus aureus membrane vesicles contain immunostimulatory DNA, RNA and peptidoglycan that activate innate immune receptors and induce autophagy. J Extracell Vesicles. 2021;10(6):e12080. doi:10.1002/jev2.12080.
   PubMed Web of Science ®Google Scholar
• Bellot P, García‐Pagán JC, Francés R, Abraldes JG, Navasa M, Pérez‐Mateo M, Such J, Bosch J. Bacterial DNA translocation is associated with systemic circulatory abnormalities and intrahepatic endothelial dysfunction in patients with cirrhosis. Hepatology. 2010;52(6):2044–2052. doi:10.1002/hep.23918.
   PubMed Web of Science ®Google Scholar
• Goto T, Lee J-Y, Teraminami A, Kim Y-I, Hirai S, Uemura T, Inoue H, Takahashi N, Kawada T. Activation of peroxisome proliferator-activated receptor-alpha stimulates both differentiation and fatty acid oxidation in adipocytes. Journal Of Lipid Research. 2011;52(5):873–884. S. doi:10.1194/jlr.M011320.
   PubMed Web of Science ®Google Scholar
• Yang X, Gonzalez FJ, Huang M, Bi H. Nuclear receptors and non-alcoholic fatty liver disease: An update. Liver Res. 2020;4(2):88–93. doi:10.1016/j.livres.2020.03.001.
   Google Scholar
• Bonnington KE, Kuehn MJ, Miller SI, Greenberg EP. Outer membrane vesicle production facilitates LPS remodeling and outer membrane maintenance in Salmonella during environmental transitions. MBio. 2016;7(5): doi:10.1128/mBio.01532-16.
   PubMed Web of Science ®Google Scholar