Loading…
Impact of host and environmental factors on β-glucuronidase enzymatic activity: implications for gastrointestinal serotonin
The gastrointestinal tract houses a reservoir of bacterial-derived enzymes that can directly catalyze the metabolism of drugs, dietary elements and endogenous molecules. Both host and environmental factors may influence this enzymatic activity, with the potential to dictate the availability of the b...
Saved in:
| Published in: | American journal of physiology: Gastrointestinal and liver physiology 2020-04, Vol.318 (4), p.G816-G826 |
|---|---|
| Main Authors: | , , , , , , , , |
| Format: | Article |
| Language: | English |
| Citations: | Items that this one cites Items that cite this one |
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| cited_by | cdi_FETCH-LOGICAL-c341t-61ac5e2348aab122213ad44f049d8d5431962070dfc8857d0dc4032293231a7a3 |
|---|---|
| cites | cdi_FETCH-LOGICAL-c341t-61ac5e2348aab122213ad44f049d8d5431962070dfc8857d0dc4032293231a7a3 |
| container_end_page | G826 |
| container_issue | 4 |
| container_start_page | G816 |
| container_title | American journal of physiology: Gastrointestinal and liver physiology |
| container_volume | 318 |
| creator | Walsh, Jacinta Olavarria-Ramirez, Loreto Lach, Gilliard Boehme, Marcus Dinan, Timothy G Cryan, John F Griffin, Brendan T Hyland, Niall P Clarke, Gerard |
| description | The gastrointestinal tract houses a reservoir of bacterial-derived enzymes that can directly catalyze the metabolism of drugs, dietary elements and endogenous molecules. Both host and environmental factors may influence this enzymatic activity, with the potential to dictate the availability of the biologically-active form of endogenous molecules in the gut and influence inter-individual variation in drug metabolism. We aimed to investigate the influence of the microbiota, and the modulation of its composition, on fecal enzymatic activity. Intrinsic factors related to the host, including age, sex and genetic background, were also explored. Fecalase, a cell-free extract of feces, was prepared and used in a colorimetric-based assay to quantify enzymatic activity. To demonstrate the functional effects of fecal enzymatic activity, we examined β-glucuronidase-mediated cleavage of serotonin β-d-glucuronide (5-HT-GLU) and the resultant production of free 5-HT by HPLC. As expected, β-glucuronidase and β-glucosidase activity were absent in germ-free mice. Enzymatic activity was significantly influenced by mouse strain and animal species. Sex and age significantly altered metabolic activity with implications for free 5-HT. β-Glucuronidase and β-glucosidase activity remained at reduced levels for nearly two weeks after cessation of antibiotic administration. This effect on fecalase corresponded to significantly lower 5-HT levels as compared with incubation with pre-antibiotic fecalase from the same mice. Dietary targeting of the microbiota using prebiotics did not alter β-glucuronidase or β-glucosidase activity. Our data demonstrate that multiple factors influence the activity of bacterial-derived enzymes which may have potential clinical implications for drug metabolism and the deconjugation of host-produced glucuronides in the gut.
This article explores a comprehensive range of host and environmental factors that introduce variability in the expression of bacterial-derived metabolic enzymes. Our results demonstrate that altered β-glucuronidase activity has implications for the bioavailability of luminal serotonin. The experimental approach employed, fecalase, provides a mechanistic basis and translational platform to further delineate the functional outputs of altered metabolic activity, and the associated physiological effects of microbiota-targeted interventions on host response to drugs and host-produced glucuronides. |
| doi_str_mv | 10.1152/ajpgi.00026.2020 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2375512355</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2375512355</sourcerecordid><originalsourceid>FETCH-LOGICAL-c341t-61ac5e2348aab122213ad44f049d8d5431962070dfc8857d0dc4032293231a7a3</originalsourceid><addsrcrecordid>eNo9kMtKLDEQhoMc0fGydyVZnk2PqUoy3ePuIN5AcKPrJibpMdKdtElaGPGpfBCfyTh6XBVUffVT9RFyBGwOIPFEPY0rN2eM4WKODNkWmZU2ViBF_YfMGCx5BY2sd8leSk-FkwiwQ3Y5glg0XMzI2_UwKp1p6OhjSJkqb6j1Ly4GP1ifVU-7Mg4x0eDpx3u16ic9laEzKtlCvq4HlZ2mBXIvLq9PqRvG3unSDD7RLkS6UinH4Hy2KTtfEpONIZcIf0C2O9Une_hT98n9xfnd2VV1c3t5ffbvptJcQK4WoLS0yEWj1AMgInBlhOiYWJrGSMFhuUBWM9PppjxrmNGCccQlRw6qVnyf_P3OHWN4nsoZ7eCStn2vvA1TapHXUgJyKQvKvlEdQ0rRdu0Y3aDiugXWfjlvN87bjfP2y3lZOf5Jnx4Ga34X_kvmn4LDgNA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2375512355</pqid></control><display><type>article</type><title>Impact of host and environmental factors on β-glucuronidase enzymatic activity: implications for gastrointestinal serotonin</title><source>American Physiological Society Free</source><creator>Walsh, Jacinta ; Olavarria-Ramirez, Loreto ; Lach, Gilliard ; Boehme, Marcus ; Dinan, Timothy G ; Cryan, John F ; Griffin, Brendan T ; Hyland, Niall P ; Clarke, Gerard</creator><creatorcontrib>Walsh, Jacinta ; Olavarria-Ramirez, Loreto ; Lach, Gilliard ; Boehme, Marcus ; Dinan, Timothy G ; Cryan, John F ; Griffin, Brendan T ; Hyland, Niall P ; Clarke, Gerard</creatorcontrib><description>The gastrointestinal tract houses a reservoir of bacterial-derived enzymes that can directly catalyze the metabolism of drugs, dietary elements and endogenous molecules. Both host and environmental factors may influence this enzymatic activity, with the potential to dictate the availability of the biologically-active form of endogenous molecules in the gut and influence inter-individual variation in drug metabolism. We aimed to investigate the influence of the microbiota, and the modulation of its composition, on fecal enzymatic activity. Intrinsic factors related to the host, including age, sex and genetic background, were also explored. Fecalase, a cell-free extract of feces, was prepared and used in a colorimetric-based assay to quantify enzymatic activity. To demonstrate the functional effects of fecal enzymatic activity, we examined β-glucuronidase-mediated cleavage of serotonin β-d-glucuronide (5-HT-GLU) and the resultant production of free 5-HT by HPLC. As expected, β-glucuronidase and β-glucosidase activity were absent in germ-free mice. Enzymatic activity was significantly influenced by mouse strain and animal species. Sex and age significantly altered metabolic activity with implications for free 5-HT. β-Glucuronidase and β-glucosidase activity remained at reduced levels for nearly two weeks after cessation of antibiotic administration. This effect on fecalase corresponded to significantly lower 5-HT levels as compared with incubation with pre-antibiotic fecalase from the same mice. Dietary targeting of the microbiota using prebiotics did not alter β-glucuronidase or β-glucosidase activity. Our data demonstrate that multiple factors influence the activity of bacterial-derived enzymes which may have potential clinical implications for drug metabolism and the deconjugation of host-produced glucuronides in the gut.
This article explores a comprehensive range of host and environmental factors that introduce variability in the expression of bacterial-derived metabolic enzymes. Our results demonstrate that altered β-glucuronidase activity has implications for the bioavailability of luminal serotonin. The experimental approach employed, fecalase, provides a mechanistic basis and translational platform to further delineate the functional outputs of altered metabolic activity, and the associated physiological effects of microbiota-targeted interventions on host response to drugs and host-produced glucuronides.</description><identifier>ISSN: 0193-1857</identifier><identifier>EISSN: 1522-1547</identifier><identifier>DOI: 10.1152/ajpgi.00026.2020</identifier><identifier>PMID: 32146834</identifier><language>eng</language><publisher>United States</publisher><ispartof>American journal of physiology: Gastrointestinal and liver physiology, 2020-04, Vol.318 (4), p.G816-G826</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c341t-61ac5e2348aab122213ad44f049d8d5431962070dfc8857d0dc4032293231a7a3</citedby><cites>FETCH-LOGICAL-c341t-61ac5e2348aab122213ad44f049d8d5431962070dfc8857d0dc4032293231a7a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32146834$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Walsh, Jacinta</creatorcontrib><creatorcontrib>Olavarria-Ramirez, Loreto</creatorcontrib><creatorcontrib>Lach, Gilliard</creatorcontrib><creatorcontrib>Boehme, Marcus</creatorcontrib><creatorcontrib>Dinan, Timothy G</creatorcontrib><creatorcontrib>Cryan, John F</creatorcontrib><creatorcontrib>Griffin, Brendan T</creatorcontrib><creatorcontrib>Hyland, Niall P</creatorcontrib><creatorcontrib>Clarke, Gerard</creatorcontrib><title>Impact of host and environmental factors on β-glucuronidase enzymatic activity: implications for gastrointestinal serotonin</title><title>American journal of physiology: Gastrointestinal and liver physiology</title><addtitle>Am J Physiol Gastrointest Liver Physiol</addtitle><description>The gastrointestinal tract houses a reservoir of bacterial-derived enzymes that can directly catalyze the metabolism of drugs, dietary elements and endogenous molecules. Both host and environmental factors may influence this enzymatic activity, with the potential to dictate the availability of the biologically-active form of endogenous molecules in the gut and influence inter-individual variation in drug metabolism. We aimed to investigate the influence of the microbiota, and the modulation of its composition, on fecal enzymatic activity. Intrinsic factors related to the host, including age, sex and genetic background, were also explored. Fecalase, a cell-free extract of feces, was prepared and used in a colorimetric-based assay to quantify enzymatic activity. To demonstrate the functional effects of fecal enzymatic activity, we examined β-glucuronidase-mediated cleavage of serotonin β-d-glucuronide (5-HT-GLU) and the resultant production of free 5-HT by HPLC. As expected, β-glucuronidase and β-glucosidase activity were absent in germ-free mice. Enzymatic activity was significantly influenced by mouse strain and animal species. Sex and age significantly altered metabolic activity with implications for free 5-HT. β-Glucuronidase and β-glucosidase activity remained at reduced levels for nearly two weeks after cessation of antibiotic administration. This effect on fecalase corresponded to significantly lower 5-HT levels as compared with incubation with pre-antibiotic fecalase from the same mice. Dietary targeting of the microbiota using prebiotics did not alter β-glucuronidase or β-glucosidase activity. Our data demonstrate that multiple factors influence the activity of bacterial-derived enzymes which may have potential clinical implications for drug metabolism and the deconjugation of host-produced glucuronides in the gut.
This article explores a comprehensive range of host and environmental factors that introduce variability in the expression of bacterial-derived metabolic enzymes. Our results demonstrate that altered β-glucuronidase activity has implications for the bioavailability of luminal serotonin. The experimental approach employed, fecalase, provides a mechanistic basis and translational platform to further delineate the functional outputs of altered metabolic activity, and the associated physiological effects of microbiota-targeted interventions on host response to drugs and host-produced glucuronides.</description><issn>0193-1857</issn><issn>1522-1547</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNo9kMtKLDEQhoMc0fGydyVZnk2PqUoy3ePuIN5AcKPrJibpMdKdtElaGPGpfBCfyTh6XBVUffVT9RFyBGwOIPFEPY0rN2eM4WKODNkWmZU2ViBF_YfMGCx5BY2sd8leSk-FkwiwQ3Y5glg0XMzI2_UwKp1p6OhjSJkqb6j1Ly4GP1ifVU-7Mg4x0eDpx3u16ic9laEzKtlCvq4HlZ2mBXIvLq9PqRvG3unSDD7RLkS6UinH4Hy2KTtfEpONIZcIf0C2O9Une_hT98n9xfnd2VV1c3t5ffbvptJcQK4WoLS0yEWj1AMgInBlhOiYWJrGSMFhuUBWM9PppjxrmNGCccQlRw6qVnyf_P3OHWN4nsoZ7eCStn2vvA1TapHXUgJyKQvKvlEdQ0rRdu0Y3aDiugXWfjlvN87bjfP2y3lZOf5Jnx4Ga34X_kvmn4LDgNA</recordid><startdate>20200401</startdate><enddate>20200401</enddate><creator>Walsh, Jacinta</creator><creator>Olavarria-Ramirez, Loreto</creator><creator>Lach, Gilliard</creator><creator>Boehme, Marcus</creator><creator>Dinan, Timothy G</creator><creator>Cryan, John F</creator><creator>Griffin, Brendan T</creator><creator>Hyland, Niall P</creator><creator>Clarke, Gerard</creator><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20200401</creationdate><title>Impact of host and environmental factors on β-glucuronidase enzymatic activity: implications for gastrointestinal serotonin</title><author>Walsh, Jacinta ; Olavarria-Ramirez, Loreto ; Lach, Gilliard ; Boehme, Marcus ; Dinan, Timothy G ; Cryan, John F ; Griffin, Brendan T ; Hyland, Niall P ; Clarke, Gerard</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c341t-61ac5e2348aab122213ad44f049d8d5431962070dfc8857d0dc4032293231a7a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Walsh, Jacinta</creatorcontrib><creatorcontrib>Olavarria-Ramirez, Loreto</creatorcontrib><creatorcontrib>Lach, Gilliard</creatorcontrib><creatorcontrib>Boehme, Marcus</creatorcontrib><creatorcontrib>Dinan, Timothy G</creatorcontrib><creatorcontrib>Cryan, John F</creatorcontrib><creatorcontrib>Griffin, Brendan T</creatorcontrib><creatorcontrib>Hyland, Niall P</creatorcontrib><creatorcontrib>Clarke, Gerard</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>American journal of physiology: Gastrointestinal and liver physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Walsh, Jacinta</au><au>Olavarria-Ramirez, Loreto</au><au>Lach, Gilliard</au><au>Boehme, Marcus</au><au>Dinan, Timothy G</au><au>Cryan, John F</au><au>Griffin, Brendan T</au><au>Hyland, Niall P</au><au>Clarke, Gerard</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Impact of host and environmental factors on β-glucuronidase enzymatic activity: implications for gastrointestinal serotonin</atitle><jtitle>American journal of physiology: Gastrointestinal and liver physiology</jtitle><addtitle>Am J Physiol Gastrointest Liver Physiol</addtitle><date>2020-04-01</date><risdate>2020</risdate><volume>318</volume><issue>4</issue><spage>G816</spage><epage>G826</epage><pages>G816-G826</pages><issn>0193-1857</issn><eissn>1522-1547</eissn><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>The gastrointestinal tract houses a reservoir of bacterial-derived enzymes that can directly catalyze the metabolism of drugs, dietary elements and endogenous molecules. Both host and environmental factors may influence this enzymatic activity, with the potential to dictate the availability of the biologically-active form of endogenous molecules in the gut and influence inter-individual variation in drug metabolism. We aimed to investigate the influence of the microbiota, and the modulation of its composition, on fecal enzymatic activity. Intrinsic factors related to the host, including age, sex and genetic background, were also explored. Fecalase, a cell-free extract of feces, was prepared and used in a colorimetric-based assay to quantify enzymatic activity. To demonstrate the functional effects of fecal enzymatic activity, we examined β-glucuronidase-mediated cleavage of serotonin β-d-glucuronide (5-HT-GLU) and the resultant production of free 5-HT by HPLC. As expected, β-glucuronidase and β-glucosidase activity were absent in germ-free mice. Enzymatic activity was significantly influenced by mouse strain and animal species. Sex and age significantly altered metabolic activity with implications for free 5-HT. β-Glucuronidase and β-glucosidase activity remained at reduced levels for nearly two weeks after cessation of antibiotic administration. This effect on fecalase corresponded to significantly lower 5-HT levels as compared with incubation with pre-antibiotic fecalase from the same mice. Dietary targeting of the microbiota using prebiotics did not alter β-glucuronidase or β-glucosidase activity. Our data demonstrate that multiple factors influence the activity of bacterial-derived enzymes which may have potential clinical implications for drug metabolism and the deconjugation of host-produced glucuronides in the gut.
This article explores a comprehensive range of host and environmental factors that introduce variability in the expression of bacterial-derived metabolic enzymes. Our results demonstrate that altered β-glucuronidase activity has implications for the bioavailability of luminal serotonin. The experimental approach employed, fecalase, provides a mechanistic basis and translational platform to further delineate the functional outputs of altered metabolic activity, and the associated physiological effects of microbiota-targeted interventions on host response to drugs and host-produced glucuronides.</abstract><cop>United States</cop><pmid>32146834</pmid><doi>10.1152/ajpgi.00026.2020</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0193-1857 |
| ispartof | American journal of physiology: Gastrointestinal and liver physiology, 2020-04, Vol.318 (4), p.G816-G826 |
| issn | 0193-1857 1522-1547 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2375512355 |
| source | American Physiological Society Free |
| title | Impact of host and environmental factors on β-glucuronidase enzymatic activity: implications for gastrointestinal serotonin |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-09-21T11%3A03%3A39IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Impact%20of%20host%20and%20environmental%20factors%20on%20%CE%B2-glucuronidase%20enzymatic%20activity:%20implications%20for%20gastrointestinal%20serotonin&rft.jtitle=American%20journal%20of%20physiology:%20Gastrointestinal%20and%20liver%20physiology&rft.au=Walsh,%20Jacinta&rft.date=2020-04-01&rft.volume=318&rft.issue=4&rft.spage=G816&rft.epage=G826&rft.pages=G816-G826&rft.issn=0193-1857&rft.eissn=1522-1547&rft_id=info:doi/10.1152/ajpgi.00026.2020&rft_dat=%3Cproquest_cross%3E2375512355%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c341t-61ac5e2348aab122213ad44f049d8d5431962070dfc8857d0dc4032293231a7a3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2375512355&rft_id=info:pmid/32146834&rfr_iscdi=true |