Evaluating microbiome-directed fibre snacks in gnotobiotic mice and humans.


Journal

Nature
ISSN: 1476-4687
Titre abrégé: Nature
Pays: England
ID NLM: 0410462

Informations de publication

Date de publication:
07 2021
Historique:
received: 01 07 2020
accepted: 25 05 2021
pubmed: 25 6 2021
medline: 10 8 2021
entrez: 24 6 2021
Statut: ppublish

Résumé

Changing food preferences brought about by westernization that have deleterious health effects

Identifiants

pubmed: 34163075
doi: 10.1038/s41586-021-03671-4
pii: 10.1038/s41586-021-03671-4
pmc: PMC8324079
mid: NIHMS1712169
doi:

Substances chimiques

Blood Proteins 0
Dietary Fiber 0
Proteome 0

Types de publication

Clinical Trial Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

91-95

Subventions

Organisme : NIH HHS
ID : DK70977
Pays : United States
Organisme : NIDDK NIH HHS
ID : P01 DK078669
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK070977
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK056341
Pays : United States
Organisme : NIH HHS
ID : DK078669
Pays : United States
Organisme : NIDDK NIH HHS
ID : F30 DK124967
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK124193
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002345
Pays : United States

Commentaires et corrections

Type : CommentIn
Type : CommentIn

Références

NCD Risk Factor Collaboration (NCD-RisC). Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19·2 million participants. Lancet 387, 1377–1396 (2016).
doi: 10.1016/S0140-6736(16)30054-X
GBD 2017 Diet Collaborators. Health effects of dietary risks in 195 countries, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 393, 1958–1972 (2019).
doi: 10.1016/S0140-6736(19)30041-8
Willett, W. et al. Food in the Anthropocene: the EAT-Lancet Commission on healthy diets from sustainable food systems. Lancet 393, 447–492 (2019).
pubmed: 30660336 doi: 10.1016/S0140-6736(18)31788-4
Hauner, H. et al. Evidence-based guideline of the German Nutrition Society: carbohydrate intake and prevention of nutrition-related diseases. Ann. Nutr. Metab. 60 (Suppl 1), 1–58 (2012).
pubmed: 22286913 doi: 10.1159/000335326
Reynolds, A. et al. Carbohydrate quality and human health: a series of systematic reviews and meta-analyses. Lancet 393, 434–445 (2019).
pubmed: 30638909 doi: 10.1016/S0140-6736(18)31809-9
Zhao, L. et al. Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes. Science 359, 1151–1156 (2018).
pubmed: 29590046 doi: 10.1126/science.aao5774
Asnicar, F. et al. Microbiome connections with host metabolism and habitual diet from 1,098 deeply phenotyped individuals. Nat. Med. 27, 321–332 (2021).
pubmed: 33432175 pmcid: 8353542 doi: 10.1038/s41591-020-01183-8
Kovatcheva-Datchary, P. et al. Dietary fiber-induced improvement in glucose metabolism is associated with increased abundance of Prevotella. Cell Metab. 22, 971–982 (2015).
pubmed: 26552345 doi: 10.1016/j.cmet.2015.10.001
Sonnenburg, E. D. et al. Specificity of polysaccharide use in intestinal Bacteroides species determines diet-induced microbiota alterations. Cell 141, 1241–1252 (2010).
pubmed: 20603004 pmcid: 2900928 doi: 10.1016/j.cell.2010.05.005
Ridaura, V. K. et al. Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science 341, 1241214 (2013).
pubmed: 24009397 doi: 10.1126/science.1241214
Patnode, M. L. et al. Interspecies competition impacts targeted manipulation of human gut bacteria by fiber-derived glycans. Cell 179, 59–73.e13 (2019).
pubmed: 31539500 pmcid: 6760872 doi: 10.1016/j.cell.2019.08.011
Lombard, V., Golaconda Ramulu, H., Drula, E., Coutinho, P. M. & Henrissat, B. The carbohydrate-active enzymes database (CAZy) in 2013. Nucleic Acids Res. 42, D490–D495 (2014).
pubmed: 24270786 doi: 10.1093/nar/gkt1178
Overbeek, R. et al. The SEED and the Rapid Annotation of microbial genomes using Subsystems Technology (RAST). Nucleic Acids Res. 42, D206–D214 (2014).
pubmed: 24293654 doi: 10.1093/nar/gkt1226
Martino, C. et al. Context-aware dimensionality reduction deconvolutes gut microbial community dynamics. Nat. Biotechnol. 39, 165–168 (2021).
pubmed: 32868914 doi: 10.1038/s41587-020-0660-7
Wesener, D. A. et al. Microbiota functional activity biosensors for characterizing nutrient metabolism in vivo. eLife 10, e64478 (2021).
pubmed: 33684031 pmcid: 7939548 doi: 10.7554/eLife.64478
Temple, M. J. et al. A Bacteroidetes locus dedicated to fungal 1,6-β-glucan degradation: Unique substrate conformation drives specificity of the key endo-1,6-β-glucanase. J. Biol. Chem. 292, 10639–10650 (2017).
pubmed: 28461332 pmcid: 5481569 doi: 10.1074/jbc.M117.787606
Larsbrink, J. et al. A discrete genetic locus confers xyloglucan metabolism in select human gut Bacteroidetes. Nature 506, 498–502 (2014).
pubmed: 24463512 pmcid: 4282169 doi: 10.1038/nature12907
Schröder, C. et al. Characterization of a theme C glycoside hydrolase family 9 endo-beta-glucanase from a biogas reactor metagenome. Protein J. 37, 454–460 (2018).
pubmed: 30123929 doi: 10.1007/s10930-018-9787-5
Shimizu, H. et al. Characterization and structural analysis of a novel exo-type enzyme acting on β-1,2-glucooligosaccharides from Parabacteroides distasonis. Biochemistry 57, 3849–3860 (2018).
pubmed: 29763309 doi: 10.1021/acs.biochem.8b00385
Li, W. et al. PspAG97A: a halophilic α-glucoside hydrolase with wide substrate specificity from glycoside hydrolase family 97. J. Microbiol. Biotechnol. 26, 1933–1942 (2016).
pubmed: 27558438 doi: 10.4014/jmb.1606.06047
Gloster, T. M., Turkenburg, J. P., Potts, J. R., Henrissat, B. & Davies, G. J. Divergence of catalytic mechanism within a glycosidase family provides insight into evolution of carbohydrate metabolism by human gut flora. Chem. Biol. 15, 1058–1067 (2008).
pubmed: 18848471 pmcid: 2670981 doi: 10.1016/j.chembiol.2008.09.005
Helbert, W. et al. Discovery of novel carbohydrate-active enzymes through the rational exploration of the protein sequences space. Proc. Natl Acad. Sci. USA 116, 6063–6068 (2019).
pubmed: 30850540 pmcid: 6442616 doi: 10.1073/pnas.1815791116
Ndeh, D. et al. Complex pectin metabolism by gut bacteria reveals novel catalytic functions. Nature 544, 65–70 (2017).
pubmed: 28329766 pmcid: 5388186 doi: 10.1038/nature21725
Hashimoto, W., Miyake, O., Ochiai, A. & Murata, K. Molecular identification of Sphingomonas sp. A1 alginate lyase (A1-IV′) as a member of novel polysaccharide lyase family 15 and implications in alginate lyase evolution. J. Biosci. Bioeng. 99, 48–54 (2005).
pubmed: 16233753 doi: 10.1263/jbb.99.48
Ritchie, M. E. et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 43, e47 (2015).
pubmed: 25605792 pmcid: 4402510 doi: 10.1093/nar/gkv007
Derecka, M. et al. Tyk2 and Stat3 regulate brown adipose tissue differentiation and obesity. Cell Metab. 16, 814–824 (2012).
pubmed: 23217260 pmcid: 3522427 doi: 10.1016/j.cmet.2012.11.005
Pedersen, L., Olsen, C. H., Pedersen, B. K. & Hojman, P. Muscle-derived expression of the chemokine CXCL1 attenuates diet-induced obesity and improves fatty acid oxidation in the muscle. Am. J. Physiol. Endocrinol. Metab. 302, E831–E840 (2012).
pubmed: 22275756 doi: 10.1152/ajpendo.00339.2011
Kraja, A. T. et al. Genetic analysis of 16 NMR-lipoprotein fractions in humans, the GOLDN study. Lipids 48, 155–165 (2013).
pubmed: 23192668 doi: 10.1007/s11745-012-3740-8
ZhuGe, D. L., Javaid, H. M. A., Sahar, N. E., Zhao, Y. Z. & Huh, J. Y. Fibroblast growth factor 2 exacerbates inflammation in adipocytes through NLRP3 inflammasome activation. Arch. Pharm. Res. 43, 1311–1324 (2020).
pubmed: 33245516 doi: 10.1007/s12272-020-01295-2
Michalak, L. et al. Microbiota-directed fibre activates both targeted and secondary metabolic shifts in the distal gut. Nat. Commun. 11, 5773 (2020).
pubmed: 33188211 pmcid: 7666174 doi: 10.1038/s41467-020-19585-0
Bucholz, K. K., Heath, A. C. & Madden, P. A. Transitions in drinking in adolescent females: evidence from the Missouri adolescent female twin study. Alcohol. Clin. Exp. Res. 24, 914–923 (2000).
pubmed: 10888082 doi: 10.1111/j.1530-0277.2000.tb02073.x
Mifflin, M. D. et al. A new predictive equation for resting energy expenditure in healthy individuals. Am. J. Clin. Nutr. 51, 241–247 (1990).
pubmed: 2305711 doi: 10.1093/ajcn/51.2.241
Subar, A. F. et al. Comparative validation of the Block, Willett, and National Cancer Institute food frequency questionnaires: the Eating at America’s Table Study. Am. J. Epidemiol. 154, 1089–1099 (2001).
pubmed: 11744511 doi: 10.1093/aje/154.12.1089
Caporaso, J. G. et al. Global patterns of 16S rRNA diversity at a depth of millions of sequences per sample. Proc. Natl Acad. Sci. USA 108 (Suppl 1), 4516–4522 (2011).
pubmed: 20534432 doi: 10.1073/pnas.1000080107
Callahan, B. J. et al. DADA2: high-resolution sample inference from Illumina amplicon data. Nat. Methods 13, 581–583 (2016).
pubmed: 27214047 pmcid: 4927377 doi: 10.1038/nmeth.3869
R Core Team. R: A Language and Environment for Statistical Computing (R Foundation for Statistical Computing, 2017).
Di Luccia, B. et al. Combined prebiotic and microbial intervention improves oral cholera vaccination responses in a mouse model of childhood undernutrition. Cell Host Microbe 27, 899–908.e5 (2020).
pubmed: 32348782 pmcid: 7292785 doi: 10.1016/j.chom.2020.04.008
Baym, M. et al. Inexpensive multiplexed library preparation for megabase-sized genomes. PLoS ONE 10, e0128036 (2015).
pubmed: 26000737 pmcid: 4441430 doi: 10.1371/journal.pone.0128036
Martin, M. Cutadapt removes adapter sequences from high-throughput sequencing reads. EMBnetJ. 17, 10–12 (2011
doi: 10.14806/ej.17.1.200
Joshi, N. A. & Fass, J. N. Sickle: A Sliding-Window, Adaptive, Quality-based Trimming tool for FastQ Files (Version 1.33) Software (2011).
Langmead, B. & Salzberg, S. L. Fast gapped-read alignment with Bowtie 2. Nat. Methods 9, 357–359 (2012).
pubmed: 22388286 pmcid: 3322381 doi: 10.1038/nmeth.1923
Peng, Y., Leung, H. C. M., Yiu, S. M. & Chin, F. Y. L. IDBA-UD: a de novo assembler for single-cell and metagenomic sequencing data with highly uneven depth. Bioinformatics 28, 1420–1428 (2012).
pubmed: 22495754 doi: 10.1093/bioinformatics/bts174
Li, D., Liu, C.-M., Luo, R., Sadakane, K. & Lam, T.-W. MEGAHIT: an ultra-fast single-node solution for large and complex metagenomics assembly via succinct de Bruijn graph. Bioinformatics 31, 1674–1676 (2015).
pubmed: 25609793 doi: 10.1093/bioinformatics/btv033
Seemann, T. Prokka: rapid prokaryotic genome annotation. Bioinformatics 30, 2068–2069 (2014).
pubmed: 24642063 doi: 10.1093/bioinformatics/btu153
Liao, Y., Smyth, G. K. & Shi, W. featureCounts: an efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics 30, 923–930 (2014).
pubmed: 24227677 doi: 10.1093/bioinformatics/btt656
Buchfink, B., Xie, C. & Huson, D. H. Fast and sensitive protein alignment using DIAMOND. Nat. Methods 12, 59–60 (2015).
pubmed: 25402007 doi: 10.1038/nmeth.3176
Camacho, C. et al. BLAST+: architecture and applications. BMC Bioinformatics 10, 421 (2009).
pubmed: 20003500 pmcid: 2803857 doi: 10.1186/1471-2105-10-421
Mistry, J., Finn, R. D., Eddy, S. R., Bateman, A. & Punta, M. Challenges in homology search: HMMER3 and convergent evolution of coiled-coil regions. Nucleic Acids Res. 41, e121 (2013).
pubmed: 23598997 pmcid: 3695513 doi: 10.1093/nar/gkt263
Chen, R. Y. et al. Duodenal microbiota in stunted undernourished children with enteropathy. N. Engl. J. Med. 383, 321–333 (2020).
pubmed: 32706533 pmcid: 7289524 doi: 10.1056/NEJMoa1916004
Plerou, V. et al. Random matrix approach to cross correlations in financial data. Phys. Rev. E 65, 066126 (2002).
doi: 10.1103/PhysRevE.65.066126
Winkler, E. S. et al. Human neutralizing antibodies against SARS-CoV-2 require intact Fc effector functions for optimal therapeutic protection. Cell 184, 1804–1820.e16 (2021).
pubmed: 33691139 pmcid: 7879018 doi: 10.1016/j.cell.2021.02.026
Zou, W. et al. Ablation of fat cells in adult mice induces massive bone gain. Cell Metab. 32, 801–813.e6 (2020).
pubmed: 33027637 doi: 10.1016/j.cmet.2020.09.011 pmcid: 7642038
Adamo, L. et al. Proteomic signatures of heart failure in relation to left ventricular ejection fraction. J. Am. Coll. Cardiol. 76, 1982–1994 (2020).
pubmed: 33092734 doi: 10.1016/j.jacc.2020.08.061 pmcid: 7584807
Tsingas, M. et al. Sox9 deletion causes severe intervertebral disc degeneration characterized by apoptosis, matrix remodeling, and compartment-specific transcriptomic changes. Matrix Biol. 94, 110–133 (2020).
pubmed: 33027692 doi: 10.1016/j.matbio.2020.09.003 pmcid: 7778523
Joly, J. H., Lowry, W. E. & Graham, N. A. Differential gene set enrichment analysis: a statistical approach to quantify the relative enrichment of two gene sets. Bioinformatics 36, 5247–5254 (2020).
pmcid: 8453775 doi: 10.1093/bioinformatics/btaa658
Wickham, H. ggplot2: Elegant Graphics for Data Analysis (Springer, 2009).
Blakeney, A. B., Harris, P. J., Henry, R. J. & Stone, B. A. A simple and rapid preparation of alditol acetates for monosaccharide analysis. Carbohydr. Res. 113, 291–299 (1983).
doi: 10.1016/0008-6215(83)88244-5
Englyst, H. N. & Cummings, J. H. Improved method for measurement of dietary fiber as non-starch polysaccharides in plant foods. J. Assoc. Off. Anal. Chem. 71, 808–814 (1988).
pubmed: 2458334
Blumenkrantz, N. & Asboe-Hansen, G. New method for quantitative determination of uronic acids. Anal. Biochem. 54, 484–489 (1973).
pubmed: 4269305 doi: 10.1016/0003-2697(73)90377-1
Thibault, J.-F. Automatisation du dosage des substances pectiques par la méthode au métahydroxydiphényle. Lebensm. Wiss. Technol. 12, 247–251 (1979).
Filisetti-Cozzi, T. M. C. C. & Carpita, N. C. Measurement of uronic acids without interference from neutral sugars. Anal. Biochem. 197, 157–162 (1991).
pubmed: 1952059 doi: 10.1016/0003-2697(91)90372-Z
Levigne, S., Thomas, M., Ralet, M.-C., Quemener, B. & Thibault, J.-F. Determination of the degrees of methylation and acetylation of pectins using a C18 column and internal standards. Food Hydrocoll. 16, 547–550 (2002).
doi: 10.1016/S0268-005X(02)00015-2
Pettolino, F. A., Walsh, C., Fincher, G. B. & Bacic, A. Determining the polysaccharide composition of plant cell walls. Nat. Protoc. 7, 1590–1607 (2012).
pubmed: 22864200 doi: 10.1038/nprot.2012.081
Buffetto, F. et al. The deconstruction of pectic rhamnogalacturonan I unmasks the occurrence of a novel arabinogalactan oligosaccharide epitope. Plant Cell Physiol. 56, 2181–2196 (2015).
pubmed: 26384432
Amicucci, M. J. et al. A rapid-throughput adaptable method for determining the monosaccharide composition of polysaccharides. Int. J. Mass Spectrom. 438, 22–28 (2019).
doi: 10.1016/j.ijms.2018.12.009
Xu, G., Amicucci, M. J., Cheng, Z., Galermo, A. G. & Lebrilla, C. B. Revisiting monosaccharide analysis - quantitation of a comprehensive set of monosaccharides using dynamic multiple reaction monitoring. Analyst 143, 200–207 (2018).
doi: 10.1039/C7AN01530E
Galermo, A. G. et al. Liquid chromatography-tandem mass spectrometry approach for determining glycosidic linkages. Anal. Chem. 90, 13073–13080 (2018).
pubmed: 30299929 pmcid: 6221975 doi: 10.1021/acs.analchem.8b04124
Galermo, A. G., Nandita, E., Castillo, J. J., Amicucci, M. J. & Lebrilla, C. B. Development of an extensive linkage library for characterization of carbohydrates. Anal. Chem. 91, 13022–13031 (2019).
pubmed: 31525948 doi: 10.1021/acs.analchem.9b03101
Cowardin, C. A. et al. Mechanisms by which sialylated milk oligosaccharides impact bone biology in a gnotobiotic mouse model of infant undernutrition. Proc. Natl Acad. Sci. USA 116, 11988–11996 (2019).
pubmed: 31138692 pmcid: 6575181 doi: 10.1073/pnas.1821770116

Auteurs

Omar Delannoy-Bruno (O)

Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St Louis, MO, USA.
Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St Louis, MO, USA.

Chandani Desai (C)

Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St Louis, MO, USA.
Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St Louis, MO, USA.

Arjun S Raman (AS)

Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St Louis, MO, USA.
Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St Louis, MO, USA.
Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, USA.

Robert Y Chen (RY)

Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St Louis, MO, USA.
Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St Louis, MO, USA.

Matthew C Hibberd (MC)

Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St Louis, MO, USA.
Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St Louis, MO, USA.
Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, USA.

Jiye Cheng (J)

Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St Louis, MO, USA.
Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St Louis, MO, USA.
Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, USA.

Nathan Han (N)

Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St Louis, MO, USA.
Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St Louis, MO, USA.

Juan J Castillo (JJ)

Department of Chemistry, University of California, Davis, CA, USA.

Garret Couture (G)

Department of Chemistry, University of California, Davis, CA, USA.

Carlito B Lebrilla (CB)

Department of Chemistry, University of California, Davis, CA, USA.

Ruteja A Barve (RA)

Department of Genetics, Washington University School of Medicine, St Louis, MO, USA.

Vincent Lombard (V)

Architecture et Fonction des Macromolécules Biologiques, Centre National de la Recherche Scientifique and Aix-Marseille Université, Marseille, France.

Bernard Henrissat (B)

Architecture et Fonction des Macromolécules Biologiques, Centre National de la Recherche Scientifique and Aix-Marseille Université, Marseille, France.
Department of Biological Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.

Semen A Leyn (SA)

Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.

Dmitry A Rodionov (DA)

Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
A. A. Kharkevich Institute for Information Transmission Problems, Russian Academy of Sciences, Moscow, Russia.

Andrei L Osterman (AL)

Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.

David K Hayashi (DK)

Mondelēz Global LLC, Chicago, IL, USA.

Alexandra Meynier (A)

Mondelēz Global LLC, Chicago, IL, USA.

Sophie Vinoy (S)

Mondelēz Global LLC, Chicago, IL, USA.

Kyleigh Kirbach (K)

Department of Medicine, Washington University School of Medicine, St Louis, MO, USA.

Tara Wilmot (T)

Department of Medicine, Washington University School of Medicine, St Louis, MO, USA.

Andrew C Heath (AC)

Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA.

Samuel Klein (S)

Department of Medicine, Washington University School of Medicine, St Louis, MO, USA.

Michael J Barratt (MJ)

Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St Louis, MO, USA.
Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St Louis, MO, USA.
Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, USA.

Jeffrey I Gordon (JI)

Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St Louis, MO, USA. jgordon@wustl.edu.
Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St Louis, MO, USA. jgordon@wustl.edu.
Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, USA. jgordon@wustl.edu.

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