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Altered gut microbiota in female mice with persistent low body weights following removal of post-weaning chronic dietary restriction
Nutritional interventions often fail to prevent growth failure in childhood and adolescent malnutrition and the mechanisms remain unclear. Recent studies revealed altered microbiota in malnourished children and anorexia nervosa. To facilitate mechanistic studies under physiologically relevant condit...
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| Published in: | Genome medicine 2016-10, Vol.8 (1), p.103-103, Article 103 |
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| creator | Chen, Jun Toyomasu, Yoshitaka Hayashi, Yujiro Linden, David R Szurszewski, Joseph H Nelson, Heidi Farrugia, Gianrico Kashyap, Purna C Chia, Nicholas Ordog, Tamas |
| description | Nutritional interventions often fail to prevent growth failure in childhood and adolescent malnutrition and the mechanisms remain unclear. Recent studies revealed altered microbiota in malnourished children and anorexia nervosa. To facilitate mechanistic studies under physiologically relevant conditions, we established a mouse model of growth failure following chronic dietary restriction and examined microbiota in relation to age, diet, body weight, and anabolic treatment.
Four-week-old female BALB/c mice (n = 12/group) were fed ad libitum (AL) or offered limited food to abolish weight gain (LF). A subset of restricted mice was treated with an insulin-like growth factor 1 (IGF1) analog. Food access was restored in a subset of untreated LF (LF-RF) and IGF1-treated LF mice (TLF-RF) on day 97. Gut microbiota were determined on days 69, 96-99 and 120 by next generation sequencing of the V3-5 region of the 16S rRNA gene. Microbiota-host factor associations were analyzed by distance-based PERMANOVA and quantified by the coefficient of determination R
for age, diet, and normalized body weight change (Δbwt). Microbial taxa on day 120 were compared following fitting with an overdispersed Poisson regression model. The machine learning algorithm Random Forests was used to predict age based on the microbiota.
On day 120, Δbwt in AL, LF, LF-RF, and TLF-RF mice was 52 ± 3, -6 ± 1*, 40 ± 3*, and 46 ± 2 % (*, P |
| doi_str_mv | 10.1186/s13073-016-0357-1 |
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Four-week-old female BALB/c mice (n = 12/group) were fed ad libitum (AL) or offered limited food to abolish weight gain (LF). A subset of restricted mice was treated with an insulin-like growth factor 1 (IGF1) analog. Food access was restored in a subset of untreated LF (LF-RF) and IGF1-treated LF mice (TLF-RF) on day 97. Gut microbiota were determined on days 69, 96-99 and 120 by next generation sequencing of the V3-5 region of the 16S rRNA gene. Microbiota-host factor associations were analyzed by distance-based PERMANOVA and quantified by the coefficient of determination R
for age, diet, and normalized body weight change (Δbwt). Microbial taxa on day 120 were compared following fitting with an overdispersed Poisson regression model. The machine learning algorithm Random Forests was used to predict age based on the microbiota.
On day 120, Δbwt in AL, LF, LF-RF, and TLF-RF mice was 52 ± 3, -6 ± 1*, 40 ± 3*, and 46 ± 2 % (*, P < 0.05 versus AL). Age and diet, but not Δbwt, were associated with gut microbiota composition. Age explained a larger proportion of the microbiota variability than diet or Δbwt. Random Forests predicted chronological age based on the microbiota and indicated microbiota immaturity in the LF mice before, but not after, refeeding. However, on day 120, the microbiota community structure of LF-RF mice was significantly different from that of both AL and LF mice. IGF1 mitigated the difference from the AL group. Refed groups had a higher abundance of Bacteroidetes and Proteobacteria and a lower abundance of Firmicutes than AL mice.
Persistent growth failure can be induced by 97-day dietary restriction in young female mice and is associated with microbiota changes seen in lean mice and individuals and anorexia nervosa. IGF1 facilitates recovery of body weights and microbiota.</description><identifier>ISSN: 1756-994X</identifier><identifier>EISSN: 1756-994X</identifier><identifier>DOI: 10.1186/s13073-016-0357-1</identifier><identifier>PMID: 27716401</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Animals ; Anorexia Nervosa - genetics ; Anorexia Nervosa - microbiology ; Anorexia Nervosa - physiopathology ; Caloric Restriction ; Development and progression ; Failure to thrive ; Feeding Behavior ; Female ; Gastrointestinal Microbiome ; Gastrointestinal Tract - microbiology ; Genetic aspects ; Growth factors ; Health aspects ; Mice ; Mice, Inbred BALB C ; Microbiota (Symbiotic organisms) ; Phylogeny ; Polymerase Chain Reaction ; RNA, Ribosomal, 16S - genetics ; Weaning ; Weight Loss - genetics</subject><ispartof>Genome medicine, 2016-10, Vol.8 (1), p.103-103, Article 103</ispartof><rights>COPYRIGHT 2016 BioMed Central Ltd.</rights><rights>The Author(s). 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c497t-ff22a6b0443e8fc7bb778cd3f764913bc7af70a6ef37d845b5fe4c7a8b0bc9cf3</citedby><cites>FETCH-LOGICAL-c497t-ff22a6b0443e8fc7bb778cd3f764913bc7af70a6ef37d845b5fe4c7a8b0bc9cf3</cites><orcidid>0000-0002-3940-7284</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5048651/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5048651/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27903,27904,36992,53769,53771</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27716401$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Jun</creatorcontrib><creatorcontrib>Toyomasu, Yoshitaka</creatorcontrib><creatorcontrib>Hayashi, Yujiro</creatorcontrib><creatorcontrib>Linden, David R</creatorcontrib><creatorcontrib>Szurszewski, Joseph H</creatorcontrib><creatorcontrib>Nelson, Heidi</creatorcontrib><creatorcontrib>Farrugia, Gianrico</creatorcontrib><creatorcontrib>Kashyap, Purna C</creatorcontrib><creatorcontrib>Chia, Nicholas</creatorcontrib><creatorcontrib>Ordog, Tamas</creatorcontrib><title>Altered gut microbiota in female mice with persistent low body weights following removal of post-weaning chronic dietary restriction</title><title>Genome medicine</title><addtitle>Genome Med</addtitle><description>Nutritional interventions often fail to prevent growth failure in childhood and adolescent malnutrition and the mechanisms remain unclear. Recent studies revealed altered microbiota in malnourished children and anorexia nervosa. To facilitate mechanistic studies under physiologically relevant conditions, we established a mouse model of growth failure following chronic dietary restriction and examined microbiota in relation to age, diet, body weight, and anabolic treatment.
Four-week-old female BALB/c mice (n = 12/group) were fed ad libitum (AL) or offered limited food to abolish weight gain (LF). A subset of restricted mice was treated with an insulin-like growth factor 1 (IGF1) analog. Food access was restored in a subset of untreated LF (LF-RF) and IGF1-treated LF mice (TLF-RF) on day 97. Gut microbiota were determined on days 69, 96-99 and 120 by next generation sequencing of the V3-5 region of the 16S rRNA gene. Microbiota-host factor associations were analyzed by distance-based PERMANOVA and quantified by the coefficient of determination R
for age, diet, and normalized body weight change (Δbwt). Microbial taxa on day 120 were compared following fitting with an overdispersed Poisson regression model. The machine learning algorithm Random Forests was used to predict age based on the microbiota.
On day 120, Δbwt in AL, LF, LF-RF, and TLF-RF mice was 52 ± 3, -6 ± 1*, 40 ± 3*, and 46 ± 2 % (*, P < 0.05 versus AL). Age and diet, but not Δbwt, were associated with gut microbiota composition. Age explained a larger proportion of the microbiota variability than diet or Δbwt. Random Forests predicted chronological age based on the microbiota and indicated microbiota immaturity in the LF mice before, but not after, refeeding. However, on day 120, the microbiota community structure of LF-RF mice was significantly different from that of both AL and LF mice. IGF1 mitigated the difference from the AL group. Refed groups had a higher abundance of Bacteroidetes and Proteobacteria and a lower abundance of Firmicutes than AL mice.
Persistent growth failure can be induced by 97-day dietary restriction in young female mice and is associated with microbiota changes seen in lean mice and individuals and anorexia nervosa. IGF1 facilitates recovery of body weights and microbiota.</description><subject>Animals</subject><subject>Anorexia Nervosa - genetics</subject><subject>Anorexia Nervosa - microbiology</subject><subject>Anorexia Nervosa - physiopathology</subject><subject>Caloric Restriction</subject><subject>Development and progression</subject><subject>Failure to thrive</subject><subject>Feeding Behavior</subject><subject>Female</subject><subject>Gastrointestinal Microbiome</subject><subject>Gastrointestinal Tract - microbiology</subject><subject>Genetic aspects</subject><subject>Growth factors</subject><subject>Health aspects</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Microbiota (Symbiotic organisms)</subject><subject>Phylogeny</subject><subject>Polymerase Chain Reaction</subject><subject>RNA, Ribosomal, 16S - genetics</subject><subject>Weaning</subject><subject>Weight Loss - genetics</subject><issn>1756-994X</issn><issn>1756-994X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><recordid>eNptUkFrFDEYHUSxtfoDvEhAKF6mJptMMnMRlqJVKHhR8BaSzJeZSGayJpkuvfvDzbBt2QXJIeHlfY-8l1dVbwm-IqTlHxOhWNAaE15j2oiaPKvOiWh43XXs1_Oj81n1KqXfGHO2YeJldbYRgnCGyXn1d-szROjRsGQ0ORODdiEr5GZkYVIeVhDQ3uUR7SAmlzLMGfmwRzr092gPbhhzQjb4grl5QBGmcKc8ChbtQsr1HtS84maMYXYG9Q6yiveFl3J0Jrswv65eWOUTvHnYL6qfXz7_uP5a336_-Xa9va0N60Surd1sFNeYMQqtNUJrIVrTUys46wjVRigrsOJgqehb1ujGAitgq7E2nbH0ovp00N0teoLeFCdRebmLbiovkkE5eXozu1EO4U42mLW8IUXgw4NADH-WYkBOLhnwXs0QliRJSxvaEcybQn1_oA4lROlmG4qiWelyy3jDmvKDK-vqP6yyeii5hxmsK_jJwOXRwAjK5zEFv6wxplMiORDLl6YUwT7ZJFiu7ZGH9sjSHrm2R6723h3n8zTxWBf6Dyh9w6A</recordid><startdate>20161003</startdate><enddate>20161003</enddate><creator>Chen, Jun</creator><creator>Toyomasu, Yoshitaka</creator><creator>Hayashi, Yujiro</creator><creator>Linden, David R</creator><creator>Szurszewski, Joseph H</creator><creator>Nelson, Heidi</creator><creator>Farrugia, Gianrico</creator><creator>Kashyap, Purna C</creator><creator>Chia, Nicholas</creator><creator>Ordog, Tamas</creator><general>BioMed Central Ltd</general><general>BioMed Central</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-3940-7284</orcidid></search><sort><creationdate>20161003</creationdate><title>Altered gut microbiota in female mice with persistent low body weights following removal of post-weaning chronic dietary restriction</title><author>Chen, Jun ; Toyomasu, Yoshitaka ; Hayashi, Yujiro ; Linden, David R ; Szurszewski, Joseph H ; Nelson, Heidi ; Farrugia, Gianrico ; Kashyap, Purna C ; Chia, Nicholas ; Ordog, Tamas</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c497t-ff22a6b0443e8fc7bb778cd3f764913bc7af70a6ef37d845b5fe4c7a8b0bc9cf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Animals</topic><topic>Anorexia Nervosa - genetics</topic><topic>Anorexia Nervosa - microbiology</topic><topic>Anorexia Nervosa - physiopathology</topic><topic>Caloric Restriction</topic><topic>Development and progression</topic><topic>Failure to thrive</topic><topic>Feeding Behavior</topic><topic>Female</topic><topic>Gastrointestinal Microbiome</topic><topic>Gastrointestinal Tract - microbiology</topic><topic>Genetic aspects</topic><topic>Growth factors</topic><topic>Health aspects</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Microbiota (Symbiotic organisms)</topic><topic>Phylogeny</topic><topic>Polymerase Chain Reaction</topic><topic>RNA, Ribosomal, 16S - genetics</topic><topic>Weaning</topic><topic>Weight Loss - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Jun</creatorcontrib><creatorcontrib>Toyomasu, Yoshitaka</creatorcontrib><creatorcontrib>Hayashi, Yujiro</creatorcontrib><creatorcontrib>Linden, David R</creatorcontrib><creatorcontrib>Szurszewski, Joseph H</creatorcontrib><creatorcontrib>Nelson, Heidi</creatorcontrib><creatorcontrib>Farrugia, Gianrico</creatorcontrib><creatorcontrib>Kashyap, Purna C</creatorcontrib><creatorcontrib>Chia, Nicholas</creatorcontrib><creatorcontrib>Ordog, Tamas</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Genome medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Jun</au><au>Toyomasu, Yoshitaka</au><au>Hayashi, Yujiro</au><au>Linden, David R</au><au>Szurszewski, Joseph H</au><au>Nelson, Heidi</au><au>Farrugia, Gianrico</au><au>Kashyap, Purna C</au><au>Chia, Nicholas</au><au>Ordog, Tamas</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Altered gut microbiota in female mice with persistent low body weights following removal of post-weaning chronic dietary restriction</atitle><jtitle>Genome medicine</jtitle><addtitle>Genome Med</addtitle><date>2016-10-03</date><risdate>2016</risdate><volume>8</volume><issue>1</issue><spage>103</spage><epage>103</epage><pages>103-103</pages><artnum>103</artnum><issn>1756-994X</issn><eissn>1756-994X</eissn><abstract>Nutritional interventions often fail to prevent growth failure in childhood and adolescent malnutrition and the mechanisms remain unclear. Recent studies revealed altered microbiota in malnourished children and anorexia nervosa. To facilitate mechanistic studies under physiologically relevant conditions, we established a mouse model of growth failure following chronic dietary restriction and examined microbiota in relation to age, diet, body weight, and anabolic treatment.
Four-week-old female BALB/c mice (n = 12/group) were fed ad libitum (AL) or offered limited food to abolish weight gain (LF). A subset of restricted mice was treated with an insulin-like growth factor 1 (IGF1) analog. Food access was restored in a subset of untreated LF (LF-RF) and IGF1-treated LF mice (TLF-RF) on day 97. Gut microbiota were determined on days 69, 96-99 and 120 by next generation sequencing of the V3-5 region of the 16S rRNA gene. Microbiota-host factor associations were analyzed by distance-based PERMANOVA and quantified by the coefficient of determination R
for age, diet, and normalized body weight change (Δbwt). Microbial taxa on day 120 were compared following fitting with an overdispersed Poisson regression model. The machine learning algorithm Random Forests was used to predict age based on the microbiota.
On day 120, Δbwt in AL, LF, LF-RF, and TLF-RF mice was 52 ± 3, -6 ± 1*, 40 ± 3*, and 46 ± 2 % (*, P < 0.05 versus AL). Age and diet, but not Δbwt, were associated with gut microbiota composition. Age explained a larger proportion of the microbiota variability than diet or Δbwt. Random Forests predicted chronological age based on the microbiota and indicated microbiota immaturity in the LF mice before, but not after, refeeding. However, on day 120, the microbiota community structure of LF-RF mice was significantly different from that of both AL and LF mice. IGF1 mitigated the difference from the AL group. Refed groups had a higher abundance of Bacteroidetes and Proteobacteria and a lower abundance of Firmicutes than AL mice.
Persistent growth failure can be induced by 97-day dietary restriction in young female mice and is associated with microbiota changes seen in lean mice and individuals and anorexia nervosa. IGF1 facilitates recovery of body weights and microbiota.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>27716401</pmid><doi>10.1186/s13073-016-0357-1</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-3940-7284</orcidid><oa>free_for_read</oa></addata></record> |
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| language | eng |
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| source | Open Access: PubMed Central; Publicly Available Content Database |
| subjects | Animals Anorexia Nervosa - genetics Anorexia Nervosa - microbiology Anorexia Nervosa - physiopathology Caloric Restriction Development and progression Failure to thrive Feeding Behavior Female Gastrointestinal Microbiome Gastrointestinal Tract - microbiology Genetic aspects Growth factors Health aspects Mice Mice, Inbred BALB C Microbiota (Symbiotic organisms) Phylogeny Polymerase Chain Reaction RNA, Ribosomal, 16S - genetics Weaning Weight Loss - genetics |
| title | Altered gut microbiota in female mice with persistent low body weights following removal of post-weaning chronic dietary restriction |
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