Effect of Akkermansia muciniphila, Faecalibacterium prausnitzii, and Their Extracellular Vesicles on the Serotonin System in Intestinal Epithelial Cells.

Akkermansia muciniphila Extracellular vesicles Faecalibacterium prausnitzii Gut microbiota Serotonergic system Serotonin

Journal

Probiotics and antimicrobial proteins
ISSN: 1867-1314
Titre abrégé: Probiotics Antimicrob Proteins
Pays: United States
ID NLM: 101484100

Informations de publication

Date de publication:
12 2021
Historique:
accepted: 07 04 2021
pubmed: 15 4 2021
medline: 8 1 2022
entrez: 14 4 2021
Statut: ppublish

Résumé

The gastrointestinal (GI) tract is an essential reservoir of serotonin or 5-hydroxytryptamine (5-HT), which possesses a set of bacterial species communities. Intestinal microbiota has the ability to modulate the host's serotonin system. In this regard, we evaluated the effect of Akkermansia muciniphila and Faecalibacterium prausnitzii along with their extracellular vesicles (EVs) on serotonin system-related genes in human epithelial colorectal adenocarcinoma (Caco-2) cells. The differentiated Caco-2 cells were treated with A. muciniphila and F. prausnitzii with the multiplicity of infection ratio of 1 and 10 and the EV concentration of 1 μg/mL and 50 μg/mL, respectively. After 24 h, the serotonin level was quantified using an ELISA kit and also the gene expression of serotonin system-related genes was examined using the quantitative real-time PCR method. According to the results, treatment with A. muciniphila and F. prausnitzii-derived EVs increased the serotonin level, while none of the bacteria could affect the serotonin level in the Caco-2 cells. Both bacteria had significant effects on the mRNA expression of serotonin system-related genes in the Caco-2 cells. Moreover, we observed that A. muciniphila and F. prausnitzii-derived EVs could impact the expression of major genes involved in the serotonin system. Our findings showed that A. muciniphila and F. prausnitzii along with their EVs could modulate serotonin system-related genes; hence, they may be useful in microbiota modulation therapies to maintain the homeostasis of the serotonin system.

Identifiants

pubmed: 33852147
doi: 10.1007/s12602-021-09786-4
pii: 10.1007/s12602-021-09786-4
doi:

Substances chimiques

Serotonin 333DO1RDJY

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1546-1556

Informations de copyright

© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Références

Belkaid Y, Harrison OJ (2017) Homeostatic immunity and the microbiota. Immunity 46:562–576. https://doi.org/10.1016/j.immuni.2017.04.008
doi: 10.1016/j.immuni.2017.04.008 pubmed: 28423337 pmcid: 5604871
Hsiao EY, McBride SW, Hsien S, Sharon G, Hyde ER, McCue T, Codelli JA, Chow J, Reisman SE, Petrosino JF (2013) Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell 155:1451–1463. https://doi.org/10.1016/j.cell.2013.11.024
doi: 10.1016/j.cell.2013.11.024 pubmed: 24315484 pmcid: 3897394
Noble EE, Hsu TM, Kanoski SE (2017) Gut to brain dysbiosis: mechanisms linking western diet consumption, the microbiome, and cognitive impairment. Front Behav Neurosci 11:9. https://doi.org/10.3389/fnbeh.2017.00009
doi: 10.3389/fnbeh.2017.00009 pubmed: 28194099 pmcid: 5277010
Ley RE, Peterson DA, Gordon JI (2006) Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell 124:837–848. https://doi.org/10.1016/j.cell.2006.02.017
doi: 10.1016/j.cell.2006.02.017 pubmed: 16497592
Gershon MD, Tack J (2007) The serotonin signaling system: from basic understanding to drug development for functional GI disorders. Gastroenterology 132:397–414. https://doi.org/10.1053/j.gastro.2006.11.002
doi: 10.1053/j.gastro.2006.11.002 pubmed: 17241888
Yano JM, Yu K, Donaldson GP, Shastri GG, Ann P, Ma L, Nagler CR, Ismagilov RF, Mazmanian SK, Hsiao EY (2015) Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell 161:264–276. https://doi.org/10.1016/j.cell.2015.02.047
doi: 10.1016/j.cell.2015.02.047 pubmed: 25860609 pmcid: 4393509
Reigstad CS, SalmonsonJFR, Szurszewski JH, Linden DR, Sonnenburg JL, Farrugia G, Kashyap PC, CE III (2015) Gut microbes promote colonic serotonin production through an effect of short-chain fatty acids on enterochromaffin cells. FASEB J 29:1395–1403. https://doi.org/10.1096/fj.14-259598
doi: 10.1096/fj.14-259598 pubmed: 25550456
Kho ZY, Lal SK (2018) The human gut microbiome—a potential controller of wellness and disease. Front Microbiol 9:1835. https://doi.org/10.3389/fmicb.2018.01835
doi: 10.3389/fmicb.2018.01835 pubmed: 30154767 pmcid: 6102370
Stasi C, Sadalla S, Milani S (2019) The relationship between the serotonin metabolism, gut-microbiota and the gut-brain axis. Curr Drug Metab 20:646–655. https://doi.org/10.2174/1389200220666190725115503
doi: 10.2174/1389200220666190725115503 pubmed: 31345143
Foxx-Orenstein AE, Chey WD (2012) Manipulation of the gut microbiota as a novel treatment strategy for gastrointestinal disorders. Am J Gastroenterol 1:41–46. https://doi.org/10.1038/ajgsup.2012.8
doi: 10.1038/ajgsup.2012.8
Collado MC, Bäuerl C, Pérez-Martínez G (2012) Defining microbiota for developing new probiotics. Microb Ecol Health Dis 23:18579. https://doi.org/10.3402/mehd.v23i0.18579
doi: 10.3402/mehd.v23i0.18579
Zhang T, Li P, Wu X, Lu G, Marcella C, Ji X, Ji G, Zhang F (2020) Alterations of Akkermansia muciniphila in the inflammatory bowel disease patients with washed microbiota transplantation. Appl Microbiol Biotechnol 104:10203–10215. https://doi.org/10.1007/s00253-020-10948-7
doi: 10.1007/s00253-020-10948-7 pubmed: 33064186
Lopez-Siles M, Enrich-Capó N, Aldeguer X, Sabat-Mir M, Duncan SH, Garcia-Gil LJ, Martinez-Medina M (2018) Alterations in the abundance and co-occurrence of Akkermansia muciniphila and Faecalibacterium prausnitzii in the colonic mucosa of inflammatory bowel disease subjects. Front Cell Infect Microbiol 8:281. https://doi.org/10.3389/fcimb.2018.00281
doi: 10.3389/fcimb.2018.00281 pubmed: 30245977 pmcid: 6137959
Singhal M, Turturice BA, Manzella CR, Ranjan R, Metwally AA, Theorell J, Huang Y, Alrefai WA, Dudeja PK, Finn PW (2019) Serotonin transporter deficiency is associated with dysbiosis and changes in metabolic function of the mouse intestinal microbiome. Sci Rep 9:1–11. https://doi.org/10.1038/s41598-019-38489-8
doi: 10.1038/s41598-019-38489-8
Lopez-Siles M, Martinez-Medina M, Surís-Valls R, Aldeguer X, Sabat-Mir M, Duncan SH, Flint HJ, Garcia-Gil LJ (2016) Changes in the abundance of Faecalibacterium prausnitzii phylogroups I and II in the intestinal mucosa of inflammatory bowel disease and patients with colorectal cancer. Inflamm Bowel Dis 22:28–41. https://doi.org/10.1097/MIB.0000000000000590
doi: 10.1097/MIB.0000000000000590 pubmed: 26595550
Lee EY, Bang JY, Park GW, Choi DS, Kang JS, Kim HJ, Park KS, Lee JO, Kim YK, Kwon KH (2007) Global proteomic profiling of native outer membrane vesicles derived from Escherichia coli. Proteomics 7:3143–3153. https://doi.org/10.1002/pmic.200700196
doi: 10.1002/pmic.200700196 pubmed: 17787032
Macia L, Nanan R, Hosseini-Beheshti E, Grau GE (2020) Host-and microbiota-derived extracellular vesicles, immune function, and disease development. Int J Mol Sci 21:107. https://doi.org/10.3390/ijms21010107
doi: 10.3390/ijms21010107
Kang C-s, Ban M, Choi E-J, Moon H-G, Jeon J-S, Kim D-K, Park S-K, Jeon SG, Roh T-Y, Myung S-J (2013) Extracellular vesicles derived from gut microbiota, especially Akkermansia muciniphila, protect the progression of dextran sulfate sodium-induced colitis. PLoS One 8:e76520. https://doi.org/10.1371/journal.pone.0076520
doi: 10.1371/journal.pone.0076520 pubmed: 24204633 pmcid: 3811976
Lee AK, Mojtahed-Jaberi M, Kyriakou T, Astarloa EA-O, Arno M, Marshall NJ, Brain SD, O’Dell SD (2010) Effect of high-fat feeding on expression of genes controlling availability of dopamine in mouse hypothalamus. Nutrition 26:411–422. https://doi.org/10.1016/j.nut.2009.05.007
doi: 10.1016/j.nut.2009.05.007 pubmed: 19811894 pmcid: 2839073
Zhong H, Dang J, Huo Z, Ma Z, Chen J, Huang Y, Zhu Y, Li M (2018) Effects of medial prefrontal cortex 5-HT7 receptor knockdown on cognitive control after acute heroin administration. Brain Res 1678:419–431. https://doi.org/10.1016/j.brainres.2017.11.002
doi: 10.1016/j.brainres.2017.11.002 pubmed: 29155092
Shao Y, Wolf PG, Guo S, Guo Y, Gaskins HR, Zhang B (2017) Zinc enhances intestinal epithelial barrier function through the PI3K/AKT/mTOR signaling pathway in Caco-2 cells. J Nutr Biochem 43:18–26. https://doi.org/10.1016/j.jnutbio.2017.01.013
doi: 10.1016/j.jnutbio.2017.01.013 pubmed: 28193579
Wettenhall JM, Smyth GK (2004) limmaGUI: a graphical user interface for linear modeling of microarray data. Bioinformatics 20:3705–3706. https://doi.org/10.1093/bioinformatics/bth449
doi: 10.1093/bioinformatics/bth449 pubmed: 15297296
Leek J, Johnson W, Parker H (2019) sva: Surrogate Variable Analysis R package version 3.10.0 2019.  https://doi.org/10.18129/B9.bioc.sva
Tian P, O’Riordan KJ, Lee Y-k, Wang G, Zhao J, Zhang H, Cryan JF, Chen W (2020) Towards a psychobiotic therapy for depression: Bifidobacterium breve CCFM1025 reverses chronic stress-induced depressive symptoms and gut microbial abnormalities in mice. Neurobiol Stress 12:100216. https://doi.org/10.1016/j.ynstr.2020.100216
doi: 10.1016/j.ynstr.2020.100216 pubmed: 32258258 pmcid: 7109524
Jin D-C, Cao H-L, Xu M-Q, Wang S-N, Wang Y-M, Yan F, Wang B-M (2016) Regulation of the serotonin transporter in the pathogenesis of irritable bowel syndrome. World J Gastroenterol 22:8137–8148. https://doi.org/10.3748/wjg.v22.i36.8137
doi: 10.3748/wjg.v22.i36.8137 pubmed: 27688655 pmcid: 5037082
Tada Y, Ishihara S, Kawashima K, Fukuba N, Sonoyama H, Kusunoki R, Oka A, Mishima Y, Oshima N, Moriyama I (2016) Downregulation of serotonin reuptake transporter gene expression in healing colonic mucosa in presence of remaining low-grade inflammation in ulcerative colitis. Gastroenterol Hepatol 31:1443–1452. https://doi.org/10.1111/jgh.13268
doi: 10.1111/jgh.13268
Clarke G, Grenham S, Scully P, Fitzgerald P, Moloney R, Shanahan F, Dinan T, Cryan J (2013) The microbiome-gut-brain axis during early life regulates the hippocampal serotonergic system in a sex-dependent manner. Mol Psychiatry 18:666–673. https://doi.org/10.1038/mp.2012.77
doi: 10.1038/mp.2012.77 pubmed: 22688187
Yaghoubfar R, Behrouzi A, Ashrafian F, Shahryari A, Moradi HR, Choopani S, Hadifar S, Vaziri F, Nojoumi SA, Fateh A (2020) Modulation of serotonin signaling/metabolism by Akkermansia muciniphila and its extracellular vesicles through the gut-brain axis in mice. Sci Rep 10:22119. https://doi.org/10.1038/s41598-020-79171-8
doi: 10.1038/s41598-020-79171-8 pubmed: 33335202 pmcid: 7747642
Ashrafian F, Shahryari A, Behrouzi A, Moradi HR, Lari A, Hadifar S, Yaghobfar R, Ahmadi Badi S, Vaziri F, Siadat SD (2019) Akkermansia muciniphila-derived extracellular vesicles as a mucosal delivery vector for amelioration of obesity in mice. Front Microbiol 10:2155. https://doi.org/10.3389/fmicb.2019.02155
doi: 10.3389/fmicb.2019.02155 pubmed: 31632356 pmcid: 6779730
Alvarez C-S, Badia J, Bosch M, Giménez R, Baldomà L (2016) 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 7:1981. https://doi.org/10.3389/fmicb.2016.01981
doi: 10.3389/fmicb.2016.01981 pubmed: 28018313 pmcid: 5156689
Fábrega MJ, Aguilera L, Giménez R, Varela E, Alexandra Canas M, Antolín M, Badía J, Baldomà L (2016) Activation of immune and defense responses in the intestinal mucosa by outer membrane vesicles of commensal and probiotic Escherichia coli strains. Front Microbiol 7:705. https://doi.org/10.3389/fmicb.2016.00705
doi: 10.3389/fmicb.2016.00705 pubmed: 27242727 pmcid: 4863414
Fukumoto S, Tatewaki M, Yamada T, Fujimiya M, Mantyh C, Voss M, Eubanks S, Harris M, Pappas TN, Takahashi T (2003) Short-chain fatty acids stimulate colonic transit via intraluminal 5-HT release in rats. Am J Physiol Regul Integr Comp Physiol 284:1269–1276. https://doi.org/10.1152/ajpregu.00442.2002
doi: 10.1152/ajpregu.00442.2002
Li H, Wang P, Huang L, Li P, Zhang D (2019) Effects of regulating gut microbiota on the serotonin metabolism in the chronic unpredictable mild stress rat model. Neurogastroenterol Motil 31:e13677. https://doi.org/10.1111/nmo.13677
doi: 10.1111/nmo.13677 pubmed: 31323174 pmcid: 6852474
Wang Y, Ge X, Wang W, Wang T, Cao H, Wang B, Wang B (2015) Lactobacillus rhamnosus GG supernatant upregulates serotonin transporter expression in intestinal epithelial cells and mice intestinal tissues. Neurogastroenterol Motil 27:1239–1248. https://doi.org/10.1111/nmo.12615
doi: 10.1111/nmo.12615 pubmed: 26088715
Cao Y-N, Feng L-J, Wang B-M, Jiang K, Li S, Xu X, Wang W-Q, Zhao J-W, Wang Y-M (2018) Lactobacillus acidophilus and Bifidobacterium longum supernatants upregulate the serotonin transporter expression in intestinal epithelial cells. Saudi J Gastroenterol 24:59. https://doi.org/10.4103/sjg.SJG_333_17
doi: 10.4103/sjg.SJG_333_17 pubmed: 29451186 pmcid: 5848327
Tsuruta T, Saito S, Osaki Y, Hamada A, Aoki-Yoshida A, Sonoyama K (2016) Organoids as an ex vivo model for studying the serotonin system in the murine small intestine and colon epithelium. Biochem Biophys Res Commun 474:161–167. https://doi.org/10.1016/j.bbrc.2016.03.165
doi: 10.1016/j.bbrc.2016.03.165 pubmed: 27105910
Fox M, Panessiti M, Moya P, Tolliver T, Chen K, Shih J, Murphy D (2013) Mutations in monoamine oxidase (MAO) genes in mice lead to hypersensitivity to serotonin-enhancing drugs: implications for drug side effects in humans. Pharmacogenomics J 13:551–557. https://doi.org/10.1038/tpj.2012.35
doi: 10.1038/tpj.2012.35 pubmed: 22964922
Shajib MS, Chauhan U, Adeeb S, Chetty Y, Armstrong D, Halder SL, Marshall JK, Khan WI (2019) Characterization of serotonin signaling components in patients with inflammatory bowel disease. J Can Assoc Gastroenterol 2:132–140. https://doi.org/10.1093/jcag/gwy039
doi: 10.1093/jcag/gwy039 pubmed: 31294376
Mawe GM, Hoffman JM (2013) Serotonin signalling in the gut—functions, dysfunctions and therapeutic targets. Nat Rev Gastroenterol Hepatol 10:473. https://doi.org/10.1038/nrgastro.2013.105
doi: 10.1038/nrgastro.2013.105 pubmed: 23797870 pmcid: 4048923
Camilleri M, Mayer E, Drossman D, Heath A, Dukes G, McSorley D, Kong S, Mangel A, Northcutt A (1999) Improvement in pain and bowel function in female irritable bowel patients with alosetron, a 5-HT3 receptor antagonist. Aliment Pharmacol Ther 13:1149–1159. https://doi.org/10.1046/j.1365-2036.1999.00610.x
doi: 10.1046/j.1365-2036.1999.00610.x pubmed: 10468696
Fujita T, Yokota S, Sawada M, Majima M, Ohtani Y, Kumagai Y (2005) Effect of MKC-733, a 5-HT3 receptor partial agonist, on bowel motility and symptoms in subjects with constipation: an exploratory study. J Clin Pharm Ther 30:611–622. https://doi.org/10.1111/j.1365-2710.2005.00695.x
doi: 10.1111/j.1365-2710.2005.00695.x pubmed: 16336295
Thomas RH, Luthin DR (2015) Current and emerging treatments for irritable bowel syndrome with constipation and chronic idiopathic constipation: focus on prosecretory agents. Pharmacotherapy 35: 613–630. https://doi.org/10.1002/phar.1594
Zhu L, Lu X, Liu L, Voglmeir J, Zhong X, Yu Q (2020) Akkermansia muciniphila protects intestinal mucosa from damage caused by S. pullorum by initiating proliferation of intestinal epithelium. Vet Res 51:1–9. https://doi.org/10.1186/s13567-020-00755-3
doi: 10.1186/s13567-020-00755-3
Reunanen J, Kainulainen V, Huuskonen L, Ottman N, Belzer C, Huhtinen H, de Vos WM, Satokari R (2015) Akkermansia muciniphila adheres to enterocytes and strengthens the integrity of the epithelial cell layer. Appl Environ Microbiol 81:3655–3662. https://doi.org/10.1128/AEM.04050-14
doi: 10.1128/AEM.04050-14 pubmed: 25795669 pmcid: 4421065
Spohn SN, Mawe GM (2017) Non-conventional features of peripheral serotonin signalling—the gut and beyond. Nat Rev Gastroenterol Hepatol 14:412–420. https://doi.org/10.1038/nrgastro.2017.51
doi: 10.1038/nrgastro.2017.51 pubmed: 28487547 pmcid: 5672796
Ashrafian F, Behrouzi A, Shahriary A, Ahmadi Badi S, Davari M, Khatami S, Rahimi Jamnani F, Fateh A, Vaziri F, Siadat SD (2019) Comparative study of effect of Akkermansia muciniphila and its extracellular vesicles on toll-like receptors and tight junction. Gastroenterol Hepatol Bed Bench 12: 163–168. https://doi.org/10.22037/ghfbb.v12i2.1537
Thompson AJ, Lummis SC (2007) The 5-HT3 receptor as a therapeutic target. Expert Opin Ther Targets 11:527–540. https://doi.org/10.1517/14728222.11.4.527
doi: 10.1517/14728222.11.4.527 pubmed: 17373882 pmcid: 1994432
Bhattarai Y, Schmidt BA, Linden DR, Larson ED, Grover M, Beyder A, Farrugia G, Kashyap PC (2017) Human-derived gut microbiota modulates colonic secretion in mice by regulating 5-HT3 receptor expression via acetate production. Am J Physiol Gastrointest Liver Physiol 313:G80–G87. https://doi.org/10.1096/fasebj.31.1_supplement.856.19
doi: 10.1096/fasebj.31.1_supplement.856.19 pubmed: 28408644 pmcid: 5538830

Auteurs

Rezvan Yaghoubfar (R)

Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran.
Microbiology Research Center (MRC), Pasteur Institute of Iran, Tehran, Iran.

Ava Behrouzi (A)

Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran.
Microbiology Research Center (MRC), Pasteur Institute of Iran, Tehran, Iran.

Ehsan Zare Banadkoki (E)

Department of Microbiology, School of Medicine, Shahed University, Tehran, Iran.

Fatemeh Ashrafian (F)

Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran.
Microbiology Research Center (MRC), Pasteur Institute of Iran, Tehran, Iran.

Arezou Lari (A)

Systems Biomedicine Unit, Pasteur Institute of Iran, Tehran, Iran.

Farzam Vaziri (F)

Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran.
Microbiology Research Center (MRC), Pasteur Institute of Iran, Tehran, Iran.

Seyed Ali Nojoumi (SA)

Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran.
Microbiology Research Center (MRC), Pasteur Institute of Iran, Tehran, Iran.

Abolfazl Fateh (A)

Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran. afateh2@gmail.com.
Microbiology Research Center (MRC), Pasteur Institute of Iran, Tehran, Iran. afateh2@gmail.com.

Shohreh Khatami (S)

Department of Biochemistry, Pasteur Institute of Iran, Tehran, Iran. sh-khatami@pasteur.ac.ir.

Seyed Davar Siadat (SD)

Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran.
Microbiology Research Center (MRC), Pasteur Institute of Iran, Tehran, Iran.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH