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Gut bacteriome and mood disorders in women with PCOS

How does the gut bacteriome differ based on mood disorders (MDs) in women with polycystic ovary syndrome (PCOS), and how can the gut bacteriome contribute to the associations between these two conditions? Women with PCOS who also have MDs exhibited a distinct gut bacteriome with reduced alpha divers...

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Published in:Human reproduction (Oxford) 2024-06, Vol.39 (6), p.1291-1302
Main Authors: Lee, S, Tejesvi, M V, Hurskainen, E, Aasmets, O, Plaza-Díaz, J, Franks, S, Morin-Papunen, L, Tapanainen, J S, Ruuska, T S, Altmäe, S, Org, E, Salumets, A, Arffman, R K, Piltonen, T T
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container_issue 6
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container_title Human reproduction (Oxford)
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creator Lee, S
Tejesvi, M V
Hurskainen, E
Aasmets, O
Plaza-Díaz, J
Franks, S
Morin-Papunen, L
Tapanainen, J S
Ruuska, T S
Altmäe, S
Org, E
Salumets, A
Arffman, R K
Piltonen, T T
description How does the gut bacteriome differ based on mood disorders (MDs) in women with polycystic ovary syndrome (PCOS), and how can the gut bacteriome contribute to the associations between these two conditions? Women with PCOS who also have MDs exhibited a distinct gut bacteriome with reduced alpha diversity and a significantly lower abundance of Butyricicoccus compared to women with PCOS but without MDs. Women with PCOS have a 4- to 5-fold higher risk of having MDs compared to women without PCOS. The gut bacteriome has been suggested to influence the pathophysiology of both PCOS and MDs. This population-based cohort study was derived from the Northern Finland Birth Cohort 1966 (NFBC1966), which includes all women born in Northern Finland in 1966. Women with PCOS who donated a stool sample at age 46 years (n = 102) and two BMI-matched controls for each case (n = 205), who also responded properly to the MD criteria scales, were included. A total of 102 women with PCOS and 205 age- and BMI-matched women without PCOS were included. Based on the validated MD criteria, the subjects were categorized into MD or no-MD groups, resulting in the following subgroups: PCOS no-MD (n = 84), PCOS MD (n = 18), control no-MD (n = 180), and control MD (n = 25). Clinical characteristics were assessed at age 31 years and age 46 years, and stool samples were collected from the women at age 46 years, followed by the gut bacteriome analysis using 16 s rRNA sequencing. Alpha diversity was assessed using observed features and Shannon's index, with a focus on genera, and beta diversity was characterized using principal components analysis (PCA) with Bray-Curtis Dissimilarity at the genus level. Associations between the gut bacteriome and PCOS-related clinical features were explored by Spearman's correlation coefficient. A P-value for multiple testing was adjusted with the Benjamini-Hochberg false discovery rate (FDR) method. We observed changes in the gut bacteriome associated with MDs, irrespective of whether the women also had PCOS. Similarly, PCOS MD cases showed a lower alpha diversity (Observed feature, PCOS no-MD, median 272; PCOS MD, median 208, FDR = 0.01; Shannon, PCOS no-MD, median 5.95; PCOS MD, median 5.57, FDR = 0.01) but also a lower abundance of Butyricicoccus (log-fold changeAnalysis of Compositions of Microbiomes with Bias Correction (ANCOM-BC)=-0.90, FDRANCOM-BC=0.04) compared to PCOS no-MD cases. In contrast, in the controls, the gut bacteriome did not differ based on M
doi_str_mv 10.1093/humrep/deae073
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Women with PCOS who also have MDs exhibited a distinct gut bacteriome with reduced alpha diversity and a significantly lower abundance of Butyricicoccus compared to women with PCOS but without MDs. Women with PCOS have a 4- to 5-fold higher risk of having MDs compared to women without PCOS. The gut bacteriome has been suggested to influence the pathophysiology of both PCOS and MDs. This population-based cohort study was derived from the Northern Finland Birth Cohort 1966 (NFBC1966), which includes all women born in Northern Finland in 1966. Women with PCOS who donated a stool sample at age 46 years (n = 102) and two BMI-matched controls for each case (n = 205), who also responded properly to the MD criteria scales, were included. A total of 102 women with PCOS and 205 age- and BMI-matched women without PCOS were included. Based on the validated MD criteria, the subjects were categorized into MD or no-MD groups, resulting in the following subgroups: PCOS no-MD (n = 84), PCOS MD (n = 18), control no-MD (n = 180), and control MD (n = 25). Clinical characteristics were assessed at age 31 years and age 46 years, and stool samples were collected from the women at age 46 years, followed by the gut bacteriome analysis using 16 s rRNA sequencing. Alpha diversity was assessed using observed features and Shannon's index, with a focus on genera, and beta diversity was characterized using principal components analysis (PCA) with Bray-Curtis Dissimilarity at the genus level. Associations between the gut bacteriome and PCOS-related clinical features were explored by Spearman's correlation coefficient. A P-value for multiple testing was adjusted with the Benjamini-Hochberg false discovery rate (FDR) method. We observed changes in the gut bacteriome associated with MDs, irrespective of whether the women also had PCOS. Similarly, PCOS MD cases showed a lower alpha diversity (Observed feature, PCOS no-MD, median 272; PCOS MD, median 208, FDR = 0.01; Shannon, PCOS no-MD, median 5.95; PCOS MD, median 5.57, FDR = 0.01) but also a lower abundance of Butyricicoccus (log-fold changeAnalysis of Compositions of Microbiomes with Bias Correction (ANCOM-BC)=-0.90, FDRANCOM-BC=0.04) compared to PCOS no-MD cases. In contrast, in the controls, the gut bacteriome did not differ based on MDs. Furthermore, in the PCOS group, Sutterella showed positive correlations with PCOS-related clinical parameters linked to obesity (BMI, r2=0.31, FDR = 0.01; waist circumference, r2=0.29, FDR = 0.02), glucose metabolism (fasting glucose, r2=0.46, FDR &lt; 0.001; fasting insulin, r2=0.24, FDR = 0.05), and gut barrier integrity (zonulin, r2=0.25, FDR = 0.03). Although this was the first study to assess the link between the gut bacteriome and MDs in PCOS and included the largest PCOS dataset for the gut microbiome analysis, the number of subjects stratified by the presence of MDs was limited when contrasted with previous studies that focused on MDs in a non-selected population. The main finding is that gut bacteriome is associated with MDs irrespective of the PCOS status, but PCOS may also modulate further the connection between the gut bacteriome and MDs. This research was funded by the European Union's Horizon 2020 Research and Innovation Programme under the Marie Sklodowska-Curie Grant Agreement (MATER, No. 813707), the Academy of Finland (project grants 315921, 321763, 336449), the Sigrid Jusélius Foundation, Novo Nordisk Foundation (NNF21OC0070372), grant numbers PID2021-12728OB-100 (Endo-Map) and CNS2022-135999 (ROSY) funded by MCIN/AEI/10.13039/501100011033 and ERFD A Way of Making Europe. The study was also supported by EU QLG1-CT-2000-01643 (EUROBLCS) (E51560), NorFA (731, 20056, 30167), USA/NIH 2000 G DF682 (50945), the Estonian Research Council (PRG1076, PRG1414), EMBO Installation (3573), and Horizon 2020 Innovation Grant (ERIN, No. EU952516). The funders did not participate in any process of the study. We have no conflicts of interest to declare. N/A.</description><identifier>ISSN: 0268-1161</identifier><identifier>ISSN: 1460-2350</identifier><identifier>EISSN: 1460-2350</identifier><identifier>DOI: 10.1093/humrep/deae073</identifier><identifier>PMID: 38614956</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Adult ; Case-Control Studies ; Cohort Studies ; Feces - microbiology ; Female ; Finland - epidemiology ; Gastrointestinal Microbiome ; Humans ; Medicin och hälsovetenskap ; Middle Aged ; Mood Disorders - epidemiology ; Original ; Polycystic Ovary Syndrome - complications ; Polycystic Ovary Syndrome - microbiology</subject><ispartof>Human reproduction (Oxford), 2024-06, Vol.39 (6), p.1291-1302</ispartof><rights>The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.</rights><rights>The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. 2024</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c364t-bc75af6aa1fadde653314983f04e1b74507f0d3270fa8993d628d159ed0f69223</cites><orcidid>0000-0001-8688-9717 ; 0000-0001-5433-4207 ; 0000-0002-0708-1865 ; 0000-0002-2259-3869 ; 0000-0002-3139-9128 ; 0000-0002-6176-0981 ; 0000-0002-1251-8160 ; 0000-0003-3277-9293 ; 0000-0002-1030-4417 ; 0000-0002-9921-7300</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38614956$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:155509565$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Lee, S</creatorcontrib><creatorcontrib>Tejesvi, M V</creatorcontrib><creatorcontrib>Hurskainen, E</creatorcontrib><creatorcontrib>Aasmets, O</creatorcontrib><creatorcontrib>Plaza-Díaz, J</creatorcontrib><creatorcontrib>Franks, S</creatorcontrib><creatorcontrib>Morin-Papunen, L</creatorcontrib><creatorcontrib>Tapanainen, J S</creatorcontrib><creatorcontrib>Ruuska, T S</creatorcontrib><creatorcontrib>Altmäe, S</creatorcontrib><creatorcontrib>Org, E</creatorcontrib><creatorcontrib>Salumets, A</creatorcontrib><creatorcontrib>Arffman, R K</creatorcontrib><creatorcontrib>Piltonen, T T</creatorcontrib><title>Gut bacteriome and mood disorders in women with PCOS</title><title>Human reproduction (Oxford)</title><addtitle>Hum Reprod</addtitle><description>How does the gut bacteriome differ based on mood disorders (MDs) in women with polycystic ovary syndrome (PCOS), and how can the gut bacteriome contribute to the associations between these two conditions? Women with PCOS who also have MDs exhibited a distinct gut bacteriome with reduced alpha diversity and a significantly lower abundance of Butyricicoccus compared to women with PCOS but without MDs. Women with PCOS have a 4- to 5-fold higher risk of having MDs compared to women without PCOS. The gut bacteriome has been suggested to influence the pathophysiology of both PCOS and MDs. This population-based cohort study was derived from the Northern Finland Birth Cohort 1966 (NFBC1966), which includes all women born in Northern Finland in 1966. Women with PCOS who donated a stool sample at age 46 years (n = 102) and two BMI-matched controls for each case (n = 205), who also responded properly to the MD criteria scales, were included. A total of 102 women with PCOS and 205 age- and BMI-matched women without PCOS were included. Based on the validated MD criteria, the subjects were categorized into MD or no-MD groups, resulting in the following subgroups: PCOS no-MD (n = 84), PCOS MD (n = 18), control no-MD (n = 180), and control MD (n = 25). Clinical characteristics were assessed at age 31 years and age 46 years, and stool samples were collected from the women at age 46 years, followed by the gut bacteriome analysis using 16 s rRNA sequencing. Alpha diversity was assessed using observed features and Shannon's index, with a focus on genera, and beta diversity was characterized using principal components analysis (PCA) with Bray-Curtis Dissimilarity at the genus level. Associations between the gut bacteriome and PCOS-related clinical features were explored by Spearman's correlation coefficient. A P-value for multiple testing was adjusted with the Benjamini-Hochberg false discovery rate (FDR) method. We observed changes in the gut bacteriome associated with MDs, irrespective of whether the women also had PCOS. Similarly, PCOS MD cases showed a lower alpha diversity (Observed feature, PCOS no-MD, median 272; PCOS MD, median 208, FDR = 0.01; Shannon, PCOS no-MD, median 5.95; PCOS MD, median 5.57, FDR = 0.01) but also a lower abundance of Butyricicoccus (log-fold changeAnalysis of Compositions of Microbiomes with Bias Correction (ANCOM-BC)=-0.90, FDRANCOM-BC=0.04) compared to PCOS no-MD cases. In contrast, in the controls, the gut bacteriome did not differ based on MDs. Furthermore, in the PCOS group, Sutterella showed positive correlations with PCOS-related clinical parameters linked to obesity (BMI, r2=0.31, FDR = 0.01; waist circumference, r2=0.29, FDR = 0.02), glucose metabolism (fasting glucose, r2=0.46, FDR &lt; 0.001; fasting insulin, r2=0.24, FDR = 0.05), and gut barrier integrity (zonulin, r2=0.25, FDR = 0.03). Although this was the first study to assess the link between the gut bacteriome and MDs in PCOS and included the largest PCOS dataset for the gut microbiome analysis, the number of subjects stratified by the presence of MDs was limited when contrasted with previous studies that focused on MDs in a non-selected population. The main finding is that gut bacteriome is associated with MDs irrespective of the PCOS status, but PCOS may also modulate further the connection between the gut bacteriome and MDs. This research was funded by the European Union's Horizon 2020 Research and Innovation Programme under the Marie Sklodowska-Curie Grant Agreement (MATER, No. 813707), the Academy of Finland (project grants 315921, 321763, 336449), the Sigrid Jusélius Foundation, Novo Nordisk Foundation (NNF21OC0070372), grant numbers PID2021-12728OB-100 (Endo-Map) and CNS2022-135999 (ROSY) funded by MCIN/AEI/10.13039/501100011033 and ERFD A Way of Making Europe. The study was also supported by EU QLG1-CT-2000-01643 (EUROBLCS) (E51560), NorFA (731, 20056, 30167), USA/NIH 2000 G DF682 (50945), the Estonian Research Council (PRG1076, PRG1414), EMBO Installation (3573), and Horizon 2020 Innovation Grant (ERIN, No. EU952516). The funders did not participate in any process of the study. We have no conflicts of interest to declare. 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Tejesvi, M V ; Hurskainen, E ; Aasmets, O ; Plaza-Díaz, J ; Franks, S ; Morin-Papunen, L ; Tapanainen, J S ; Ruuska, T S ; Altmäe, S ; Org, E ; Salumets, A ; Arffman, R K ; Piltonen, T T</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c364t-bc75af6aa1fadde653314983f04e1b74507f0d3270fa8993d628d159ed0f69223</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Adult</topic><topic>Case-Control Studies</topic><topic>Cohort Studies</topic><topic>Feces - microbiology</topic><topic>Female</topic><topic>Finland - epidemiology</topic><topic>Gastrointestinal Microbiome</topic><topic>Humans</topic><topic>Medicin och hälsovetenskap</topic><topic>Middle Aged</topic><topic>Mood Disorders - epidemiology</topic><topic>Original</topic><topic>Polycystic Ovary Syndrome - complications</topic><topic>Polycystic Ovary Syndrome - microbiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lee, S</creatorcontrib><creatorcontrib>Tejesvi, M V</creatorcontrib><creatorcontrib>Hurskainen, E</creatorcontrib><creatorcontrib>Aasmets, O</creatorcontrib><creatorcontrib>Plaza-Díaz, J</creatorcontrib><creatorcontrib>Franks, S</creatorcontrib><creatorcontrib>Morin-Papunen, L</creatorcontrib><creatorcontrib>Tapanainen, J S</creatorcontrib><creatorcontrib>Ruuska, T S</creatorcontrib><creatorcontrib>Altmäe, S</creatorcontrib><creatorcontrib>Org, E</creatorcontrib><creatorcontrib>Salumets, A</creatorcontrib><creatorcontrib>Arffman, R K</creatorcontrib><creatorcontrib>Piltonen, T T</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><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Freely available online</collection><collection>SwePub Articles full text</collection><jtitle>Human reproduction (Oxford)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lee, S</au><au>Tejesvi, M V</au><au>Hurskainen, E</au><au>Aasmets, O</au><au>Plaza-Díaz, J</au><au>Franks, S</au><au>Morin-Papunen, L</au><au>Tapanainen, J S</au><au>Ruuska, T S</au><au>Altmäe, S</au><au>Org, E</au><au>Salumets, A</au><au>Arffman, R K</au><au>Piltonen, T T</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Gut bacteriome and mood disorders in women with PCOS</atitle><jtitle>Human reproduction (Oxford)</jtitle><addtitle>Hum Reprod</addtitle><date>2024-06-03</date><risdate>2024</risdate><volume>39</volume><issue>6</issue><spage>1291</spage><epage>1302</epage><pages>1291-1302</pages><issn>0268-1161</issn><issn>1460-2350</issn><eissn>1460-2350</eissn><abstract>How does the gut bacteriome differ based on mood disorders (MDs) in women with polycystic ovary syndrome (PCOS), and how can the gut bacteriome contribute to the associations between these two conditions? Women with PCOS who also have MDs exhibited a distinct gut bacteriome with reduced alpha diversity and a significantly lower abundance of Butyricicoccus compared to women with PCOS but without MDs. Women with PCOS have a 4- to 5-fold higher risk of having MDs compared to women without PCOS. The gut bacteriome has been suggested to influence the pathophysiology of both PCOS and MDs. This population-based cohort study was derived from the Northern Finland Birth Cohort 1966 (NFBC1966), which includes all women born in Northern Finland in 1966. Women with PCOS who donated a stool sample at age 46 years (n = 102) and two BMI-matched controls for each case (n = 205), who also responded properly to the MD criteria scales, were included. A total of 102 women with PCOS and 205 age- and BMI-matched women without PCOS were included. Based on the validated MD criteria, the subjects were categorized into MD or no-MD groups, resulting in the following subgroups: PCOS no-MD (n = 84), PCOS MD (n = 18), control no-MD (n = 180), and control MD (n = 25). Clinical characteristics were assessed at age 31 years and age 46 years, and stool samples were collected from the women at age 46 years, followed by the gut bacteriome analysis using 16 s rRNA sequencing. Alpha diversity was assessed using observed features and Shannon's index, with a focus on genera, and beta diversity was characterized using principal components analysis (PCA) with Bray-Curtis Dissimilarity at the genus level. Associations between the gut bacteriome and PCOS-related clinical features were explored by Spearman's correlation coefficient. A P-value for multiple testing was adjusted with the Benjamini-Hochberg false discovery rate (FDR) method. We observed changes in the gut bacteriome associated with MDs, irrespective of whether the women also had PCOS. Similarly, PCOS MD cases showed a lower alpha diversity (Observed feature, PCOS no-MD, median 272; PCOS MD, median 208, FDR = 0.01; Shannon, PCOS no-MD, median 5.95; PCOS MD, median 5.57, FDR = 0.01) but also a lower abundance of Butyricicoccus (log-fold changeAnalysis of Compositions of Microbiomes with Bias Correction (ANCOM-BC)=-0.90, FDRANCOM-BC=0.04) compared to PCOS no-MD cases. In contrast, in the controls, the gut bacteriome did not differ based on MDs. Furthermore, in the PCOS group, Sutterella showed positive correlations with PCOS-related clinical parameters linked to obesity (BMI, r2=0.31, FDR = 0.01; waist circumference, r2=0.29, FDR = 0.02), glucose metabolism (fasting glucose, r2=0.46, FDR &lt; 0.001; fasting insulin, r2=0.24, FDR = 0.05), and gut barrier integrity (zonulin, r2=0.25, FDR = 0.03). Although this was the first study to assess the link between the gut bacteriome and MDs in PCOS and included the largest PCOS dataset for the gut microbiome analysis, the number of subjects stratified by the presence of MDs was limited when contrasted with previous studies that focused on MDs in a non-selected population. The main finding is that gut bacteriome is associated with MDs irrespective of the PCOS status, but PCOS may also modulate further the connection between the gut bacteriome and MDs. This research was funded by the European Union's Horizon 2020 Research and Innovation Programme under the Marie Sklodowska-Curie Grant Agreement (MATER, No. 813707), the Academy of Finland (project grants 315921, 321763, 336449), the Sigrid Jusélius Foundation, Novo Nordisk Foundation (NNF21OC0070372), grant numbers PID2021-12728OB-100 (Endo-Map) and CNS2022-135999 (ROSY) funded by MCIN/AEI/10.13039/501100011033 and ERFD A Way of Making Europe. The study was also supported by EU QLG1-CT-2000-01643 (EUROBLCS) (E51560), NorFA (731, 20056, 30167), USA/NIH 2000 G DF682 (50945), the Estonian Research Council (PRG1076, PRG1414), EMBO Installation (3573), and Horizon 2020 Innovation Grant (ERIN, No. EU952516). The funders did not participate in any process of the study. We have no conflicts of interest to declare. N/A.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>38614956</pmid><doi>10.1093/humrep/deae073</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0001-8688-9717</orcidid><orcidid>https://orcid.org/0000-0001-5433-4207</orcidid><orcidid>https://orcid.org/0000-0002-0708-1865</orcidid><orcidid>https://orcid.org/0000-0002-2259-3869</orcidid><orcidid>https://orcid.org/0000-0002-3139-9128</orcidid><orcidid>https://orcid.org/0000-0002-6176-0981</orcidid><orcidid>https://orcid.org/0000-0002-1251-8160</orcidid><orcidid>https://orcid.org/0000-0003-3277-9293</orcidid><orcidid>https://orcid.org/0000-0002-1030-4417</orcidid><orcidid>https://orcid.org/0000-0002-9921-7300</orcidid><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 0268-1161
ispartof Human reproduction (Oxford), 2024-06, Vol.39 (6), p.1291-1302
issn 0268-1161
1460-2350
1460-2350
language eng
recordid cdi_swepub_primary_oai_swepub_ki_se_857692
source Oxford Journals Online
subjects Adult
Case-Control Studies
Cohort Studies
Feces - microbiology
Female
Finland - epidemiology
Gastrointestinal Microbiome
Humans
Medicin och hälsovetenskap
Middle Aged
Mood Disorders - epidemiology
Original
Polycystic Ovary Syndrome - complications
Polycystic Ovary Syndrome - microbiology
title Gut bacteriome and mood disorders in women with PCOS
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