1-Deoxynojirimycin containing Morus alba leaf-based food modulates the gut microbiome and expression of genes related to obesity.
Diabetes
Microbiome
Natural products
Obesity
Pathways
Transcriptome
Journal
BMC veterinary research
ISSN: 1746-6148
Titre abrégé: BMC Vet Res
Pays: England
ID NLM: 101249759
Informations de publication
Date de publication:
03 Apr 2024
03 Apr 2024
Historique:
received:
29
07
2023
accepted:
28
02
2024
medline:
4
4
2024
pubmed:
4
4
2024
entrez:
3
4
2024
Statut:
epublish
Résumé
Obesity is a serious disease with an alarmingly high incidence that can lead to other complications in both humans and dogs. Similar to humans, obesity can cause metabolic diseases such as diabetes in dogs. Natural products may be the preferred intervention for metabolic diseases such as obesity. The compound 1-deoxynojirimycin, present in Morus leaves and other sources has antiobesity effects. The possible antiobesity effect of 1-deoxynojirimycin containing Morus alba leaf-based food was studied in healthy companion dogs (n = 46) visiting the veterinary clinic without a history of diseases. Body weight, body condition score (BCS), blood-related parameters, and other vital parameters of the dogs were studied. Whole-transcriptome of blood and gut microbiome analysis was also carried out to investigate the possible mechanisms of action and role of changes in the gut microbiome due to treatment. After 90 days of treatment, a significant antiobesity effect of the treatment food was observed through the reduction of weight, BCS, and blood-related parameters. A whole-transcriptome study revealed differentially expressed target genes important in obesity and diabetes-related pathways such as MLXIPL, CREB3L1, EGR1, ACTA2, SERPINE1, NOTCH3, and CXCL8. Gut microbiome analysis also revealed a significant difference in alpha and beta-diversity parameters in the treatment group. Similarly, the microbiota known for their health-promoting effects such as Lactobacillus ruminis, and Weissella hellenica were abundant (increased) in the treatment group. The predicted functional pathways related to obesity were also differentially abundant between groups. 1-Deoxynojirimycin-containing treatment food have been shown to significantly improve obesity. The identified genes, pathways, and gut microbiome-related results may be pursued in further studies to develop 1-deoxynojirimycin-based products as candidates against obesity.
Sections du résumé
BACKGROUND
BACKGROUND
Obesity is a serious disease with an alarmingly high incidence that can lead to other complications in both humans and dogs. Similar to humans, obesity can cause metabolic diseases such as diabetes in dogs. Natural products may be the preferred intervention for metabolic diseases such as obesity. The compound 1-deoxynojirimycin, present in Morus leaves and other sources has antiobesity effects. The possible antiobesity effect of 1-deoxynojirimycin containing Morus alba leaf-based food was studied in healthy companion dogs (n = 46) visiting the veterinary clinic without a history of diseases. Body weight, body condition score (BCS), blood-related parameters, and other vital parameters of the dogs were studied. Whole-transcriptome of blood and gut microbiome analysis was also carried out to investigate the possible mechanisms of action and role of changes in the gut microbiome due to treatment.
RESULTS
RESULTS
After 90 days of treatment, a significant antiobesity effect of the treatment food was observed through the reduction of weight, BCS, and blood-related parameters. A whole-transcriptome study revealed differentially expressed target genes important in obesity and diabetes-related pathways such as MLXIPL, CREB3L1, EGR1, ACTA2, SERPINE1, NOTCH3, and CXCL8. Gut microbiome analysis also revealed a significant difference in alpha and beta-diversity parameters in the treatment group. Similarly, the microbiota known for their health-promoting effects such as Lactobacillus ruminis, and Weissella hellenica were abundant (increased) in the treatment group. The predicted functional pathways related to obesity were also differentially abundant between groups.
CONCLUSIONS
CONCLUSIONS
1-Deoxynojirimycin-containing treatment food have been shown to significantly improve obesity. The identified genes, pathways, and gut microbiome-related results may be pursued in further studies to develop 1-deoxynojirimycin-based products as candidates against obesity.
Identifiants
pubmed: 38570815
doi: 10.1186/s12917-024-03961-9
pii: 10.1186/s12917-024-03961-9
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
133Subventions
Organisme : Korea Institute of Marine Science & Technology Promotion (KIMST) funded by the Ministry of Oceans and Fisheries
ID : RS-2023-00236592
Informations de copyright
© 2024. The Author(s).
Références
Lee HR, Shin J, Han K, Chang J, Jeong S-M, Chon SJ, et al. Obesity and risk of diabetes Mellitus by Menopausal Status: a Nationwide Cohort Study. J Clin Med. 2021;10(21):5189.
pubmed: 34768709
pmcid: 8584465
doi: 10.3390/jcm10215189
Cho YJ, Park S, Kim SS, Park HJ, Son JW, Lee TK, et al. The Gangwon obesity and metabolic syndrome study: methods and initial Baseline Data. JOMES. 2022;31(4):303–12.
pubmed: 36581590
pmcid: 9828700
doi: 10.7570/jomes22064
McGreevy PD, Thomson PC, Pride C, Fawcett A, Grassi T, Jones B. Prevalence of obesity in dogs examined by Australian veterinary practices and the risk factors involved. Vet Rec. 2005;156(22):695–702.
pubmed: 15923551
doi: 10.1136/vr.156.22.695
Bergman RN, Kim SP, Hsu IR, Catalano KJ, Chiu JD, Kabir M, et al. Abdominal obesity: role in the pathophysiology of metabolic disease and cardiovascular risk. Am J Med. 2007;120(2):S3–8.
pubmed: 17296343
doi: 10.1016/j.amjmed.2006.11.012
Thengchaisri N, Theerapun W, Kaewmokul S, Sastravaha A. Abdominal obesity is associated with heart disease in dogs. BMC Vet Res. 2014;10(1):1–7.
doi: 10.1186/1746-6148-10-131
Finlayson G. Food addiction and obesity: unnecessary medicalization of hedonic overeating. Nat Reviews Endocrinol. 2017;13(8):493–8.
doi: 10.1038/nrendo.2017.61
Berthoud H-R, Münzberg H, Morrison CD. Blaming the brain for obesity: integration of hedonic and homeostatic mechanisms. Gastroenterology. 2017;152(7):1728–38.
pubmed: 28192106
doi: 10.1053/j.gastro.2016.12.050
Friedman JM. Leptin and the endocrine control of energy balance. Nat Metabolism. 2019;1(8):754–64.
doi: 10.1038/s42255-019-0095-y
Winer DA, Luck H, Tsai S, Winer S. The intestinal immune system in obesity and insulin resistance. Cell Metabol. 2016;23(3):413–26.
doi: 10.1016/j.cmet.2016.01.003
Vu CC, Verstegen M, Hendriks W, Pham K. The nutritive value of mulberry leaves (Morus alba) and partial replacement of cotton seed in rations on the performance of growing Vietnamese cattle. Asian-Australasian J Anim Sci. 2011;24(9):1233–42.
doi: 10.5713/ajas.2011.90328
Zhang R, Zhang Q, Zhu S, Liu B, Liu F, Xu Y. Mulberry leaf (Morus alba L.): a review of its potential influences in mechanisms of action on metabolic diseases. Pharmacol Res. 2022;175:106029.
pubmed: 34896248
doi: 10.1016/j.phrs.2021.106029
Morus alba (Mulberry), Protects TNF-α-Induced Human Dermal Fibroblast Damage. Antioxidants.2022;11(10):1894.
O-β-d-Glucopyranosyl-4,6-dihydroxybenzaldehyde Isolated from Morus alba (Mulberry) Fruits Suppresses Damage by Regulating Oxidative and Inflammatory Responses in TNF-α-Induced Human Dermal Fibroblasts. International Journal of Molecular Sciences. 2022;23(23):14802.
Metwally FM, Rashad H, Mahmoud AA. Morus alba L. diminishes visceral adiposity, insulin resistance, behavioral alterations via regulation of gene expression of leptin, resistin and adiponectin in rats fed a high-cholesterol diet. Physiol Behav. 2019;201:1–11.
pubmed: 30552920
doi: 10.1016/j.physbeh.2018.12.010
Kojima Y, Kimura T, Nakagawa K, Asai A, Hasumi K, Oikawa S, et al. Effects of mulberry leaf extract rich in 1-deoxynojirimycin on blood lipid profiles in humans. J Clin Biochem Nutr. 2010;47(2):155–61.
pubmed: 20838571
pmcid: 2935155
doi: 10.3164/jcbn.10-53
Kimura T, Nakagawa K, Kubota H, Kojima Y, Goto Y, Yamagishi K, et al. Food-grade mulberry powder enriched with 1-deoxynojirimycin suppresses the elevation of postprandial blood glucose in humans. J Agric Food Chem. 2007;55(14):5869–74.
pubmed: 17555327
doi: 10.1021/jf062680g
Kong W-H, Oh S-H, Ahn Y-R, Kim K-W, Kim J-H, Seo S-W. Antiobesity effects and improvement of insulin sensitivity by 1-deoxynojirimycin in animal models. J Agric Food Chem. 2008;56(8):2613–9.
pubmed: 18363357
doi: 10.1021/jf073223i
Iftikhar M, Lu Y, Zhou M. An overview of therapeutic potential of N-alkylated 1-deoxynojirimycin congeners. Carbohydr Res. 2021;504:108317.
pubmed: 33932806
doi: 10.1016/j.carres.2021.108317
Park M, Jaiswal V, Kim K, Chun J, Lee M-J, Shin J-H, et al. Mulberry Leaf supplements effecting anti-inflammatory genes and improving obesity in Elderly overweight dogs. Int J Mol Sci. 2022;23(23):15215.
pubmed: 36499541
pmcid: 9735752
doi: 10.3390/ijms232315215
Guleria V, Jaiswal V. Comparative transcriptome analysis of different stages of Plasmodium Falciparum to explore vaccine and drug candidates. Genomics. 2020;112(1):796–804.
pubmed: 31128264
doi: 10.1016/j.ygeno.2019.05.018
Jaiswal V, Cho Y-I, Lee H-J. Preliminary study to explore the immune-enhancement mechanism of platycodon grandiflorus extract through comparative transcriptome analysis. Appl Sci. 2020;11(1):226.
doi: 10.3390/app11010226
Jaiswal V, Park M, Lee H-J. Comparative transcriptome analysis of the expression of antioxidant and immunity genes in the spleen of a cyanidin 3-O-Glucoside-treated alzheimer’s mouse model. Antioxidants. 2021;10(9):1435.
pubmed: 34573067
pmcid: 8472539
doi: 10.3390/antiox10091435
Nam S, Lee Y. Genome-scale metabolic model analysis of metabolic differences between Lauren Diffuse and intestinal subtypes in gastric Cancer. Cancers. 2022;14(9):2340.
pubmed: 35565469
pmcid: 9104812
doi: 10.3390/cancers14092340
Li W-Z, Stirling K, Yang J-J, Zhang L. Gut microbiota and diabetes: from correlation to causality and mechanism. World J Diabetes. 2020;11(7):293.
pubmed: 32843932
pmcid: 7415231
doi: 10.4239/wjd.v11.i7.293
Aoun A, Darwish F, Hamod N. The influence of the gut microbiome on obesity in adults and the role of probiotics, prebiotics, and synbiotics for weight loss. Prev Nutr food Sci. 2020;25(2):113.
pubmed: 32676461
pmcid: 7333005
doi: 10.3746/pnf.2020.25.2.113
Kim HR, Seo E, Oh S, Seo M, Byun K, Kim B-Y. Anti-obesity effects of Multi-strain Probiotics in mice with high-carbohydrate Diet-Induced obesity and the underlying Molecular mechanisms. Nutrients. 2022;14(23):5173.
pubmed: 36501204
pmcid: 9739441
doi: 10.3390/nu14235173
Choi MJ, Yu H, Kim JI, Seo H, Kim JG, Kim S-K, et al. Anti-obesity effects of lactiplantibacillus plantarum SKO-001 in high-fat diet-induced obese mice. Eur J Nutr. 2023;62(4):1611–22.
pubmed: 36729332
pmcid: 10195764
doi: 10.1007/s00394-023-03096-x
Park M, Kim KH, Jaiswal V, Choi J, Chun JL, Seo KM, et al. Effect of black ginseng and silkworm supplementation on obesity, the transcriptome, and the gut microbiome of diet-induced overweight dogs. Sci Rep. 2021;11(1):16334.
pubmed: 34381138
pmcid: 8358025
doi: 10.1038/s41598-021-95789-8
Frye CW, Mann S, Joseph JL, Hansen C, Sass B, Wakshlag JJ. Serum biochemistry and inflammatory cytokines in racing endurance sled dogs with and without rhabdomyolysis. Front Veterinary Sci. 2018;5:145.
doi: 10.3389/fvets.2018.00145
Medicine CUCoV. Animal Health Diagnostic Center Cornell University College of Veterinary Medicine; [Available from: https://www.vet.cornell.edu/animal-health-diagnostic-center/laboratories/clinical-pathology/reference-intervals/chemistry . Accessed 12 February 2024.
Taweechotipatr M, Iyer C, Spinler JK, Versalovic J, Tumwasorn S. Lactobacillus saerimneri and Lactobacillus ruminis: novel human-derived probiotic strains with immunomodulatory activities. FEMS Microbiol Lett. 2009;293(1):65–72.
pubmed: 19222575
doi: 10.1111/j.1574-6968.2009.01506.x
Cai Y, Benno Y, Nakase T, Oh T-K. Specific probiotic characterization of Weissella hellenica DS-12 isolated from flounder intestine. J Gen Appl Microbiol. 1998;44(5):311–6.
pubmed: 12501410
doi: 10.2323/jgam.44.311
Lee S, Nguyen QN, Kim SJ, Lee J, Shin M-S. Estrogenic activity of freeze-dried silkworm extracts through the activation of estrogen receptors in MCF-7 cells. Appl Biol Chem. 2022;65(1):43.
doi: 10.1186/s13765-022-00714-w
Jalili V, Poorahmadi Z, Hasanpour Ardekanizadeh N, Gholamalizadeh M, Ajami M, Houshiarrad A, et al. The association between obesity with serum levels of liver enzymes, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and gamma-glutamyl transferase in adult women. Endocrinol Diabetes Metabolism. 2022;5(6):e367.
doi: 10.1002/edm2.367
DH L. Is serum gamma glutamyltransferase a marker of oxidative stress? Free Radic Res. 2004;38:535–9.
doi: 10.1080/10715760410001694026
Coku V, Shkembi X. Serum Gamma-glutamyltransferase and obesity: is there a link? Med Archives. 2018;72(2):112.
doi: 10.5455/medarh.2017.72.112-115
Bai C, Zhang M, Zhang Y, He Y, Dou H, Wang Z, et al. Gamma-Glutamyltransferase activity (GGT) is a long-sought biomarker of Redox Status in blood circulation: a retrospective clinical study of 44 types of Human diseases. Oxidative Med Cell Longev. 2022;2022:8494076.
doi: 10.1155/2022/8494076
Lee W-J, Shim W-S. Rg3-enriched Korean red ginseng alleviates chloroquine-induced itch and dry skin pruritus in an MrgprA3-dependent manner in mice. Integr Med Res. 2023;12(1):100916.
pubmed: 36632132
doi: 10.1016/j.imr.2022.100916
Park A, Choi SJ, Park S, Kim SM, Lee HE, Joo M, et al. Plasma Aldo-Keto Reductase Family 1 Member B10 as a Biomarker performs well in the diagnosis of nonalcoholic steatohepatitis and fibrosis. Int J Mol Sci. 2022;23(9):5035.
pubmed: 35563425
pmcid: 9101253
doi: 10.3390/ijms23095035
Park J-W, Kilic O, Deo M, Jimenez-Cowell K, Demirdizen E, Kim H, et al. CIC reduces xCT/SLC7A11 expression and glutamate release in glioma. Acta Neuropathol Commun. 2023;11(1):13.
pubmed: 36647117
pmcid: 9843885
doi: 10.1186/s40478-023-01507-y
Lima RS, Mattos RT, Medeiros NI, Kattah FM, Nascimento JR, Menezes CA, et al. CXCL8 expression and methylation are correlated with anthropometric and metabolic parameters in childhood obesity. Cytokine. 2021;143:155538.
pubmed: 33926776
doi: 10.1016/j.cyto.2021.155538
Kim C, Park H, Kawada T, Kim JH, Lim D, Hubbard N, et al. Circulating levels of MCP-1 and IL-8 are elevated in human obese subjects and associated with obesity-related parameters. Int J Obes. 2006;30(9):1347–55.
doi: 10.1038/sj.ijo.0803259
Song E-J, Lee E-S, So Y-S, Lee C-Y, Nam Y-D, Lee B-H, et al. Modulation of gut microbiota by rice starch enzymatically modified using amylosucrase from Deinococcus geothermalis. Food Sci Biotechnol. 2023;32(4):565–75.
pubmed: 36911326
pmcid: 9992496
doi: 10.1007/s10068-022-01238-1
Pinart M, Dötsch A, Schlicht K, Laudes M, Bouwman J, Forslund SK, et al. Gut microbiome composition in obese and non-obese persons: a systematic review and meta-analysis. Nutrients. 2021;14(1):12.
pubmed: 35010887
pmcid: 8746372
doi: 10.3390/nu14010012
Wiciński M, Gębalski J, Gołębiewski J, Malinowski B. Probiotics for the treatment of overweight and obesity in humans—a review of clinical trials. Microorganisms. 2020;8(8):1148.
pubmed: 32751306
pmcid: 7465252
doi: 10.3390/microorganisms8081148
Marques AM, Sarandy MM, Novaes RD, Gonçalves RV, Freitas MB. Preclinical relevance of probiotics in type 2 diabetes: a systematic review. Int J Exp Pathol. 2020;101(3–4):68–79.
pubmed: 32608551
pmcid: 7370849
doi: 10.1111/iep.12359
Wan Y, Yuan J, Li J, Li H, Yin K, Wang F, et al. Overweight and underweight status are linked to specific gut microbiota and intestinal tricarboxylic acid cycle intermediates. Clin Nutr. 2020;39(10):3189–98.
pubmed: 32164980
doi: 10.1016/j.clnu.2020.02.014
Zhang J, Xiao Y, Hu J, Liu S, Zhou Z, Xie L. Lipid metabolism in type 1 diabetes mellitus: pathogenetic and therapeutic implications. Front Immunol. 2022;13.
Song Y, Shen H, Liu T, Pan B, De Alwis S, Zhang W, et al. Effects of three different mannans on obesity and gut microbiota in high-fat diet-fed C57BL/6J mice. Food Funct. 2021;12(10):4606–20.
pubmed: 33908936
doi: 10.1039/D0FO03331F
Elshorbagy AK, Kozich V, Smith AD, Refsum H. Cysteine and obesity: consistency of the evidence across epidemiologic, animal and cellular studies. Curr Opin Clin Nutr Metabolic Care. 2012;15(1):49–57.
doi: 10.1097/MCO.0b013e32834d199f
Maltais-Payette I, Boulet M-M, Prehn C, Adamski J, Tchernof A. Circulating glutamate concentration as a biomarker of visceral obesity and associated metabolic alterations. Nutr Metabolism. 2018;15:1–7.
doi: 10.1186/s12986-018-0316-5
Maguire D, Talwar D, Shiels PG, McMillan D. The role of thiamine dependent enzymes in obesity and obesity related chronic disease states: a systematic review. Clin Nutr ESPEN. 2018;25:8–17.
pubmed: 29779823
doi: 10.1016/j.clnesp.2018.02.007
Liu W, Fang X, Zhou Y, Dou L, Dou T. Machine learning-based investigation of the relationship between gut microbiome and obesity status. Microbes Infect. 2022;24(2):104892.
pubmed: 34678464
doi: 10.1016/j.micinf.2021.104892
Yuan X, Chen R, McCormick KL, Zhang Y, Lin X, Yang X. The role of the gut microbiota on the metabolic status of obese children. Microb Cell Fact. 2021;20:1–13.
doi: 10.1186/s12934-021-01548-9
Elshorbagy AK, Valdivia-Garcia M, Refsum H, Butte N. The association of cysteine with obesity, inflammatory cytokines and insulin resistance in Hispanic children and adolescents. 2012.
Kerns JC, Arundel C, Chawla LS. Thiamin deficiency in people with obesity. Adv Nutr. 2015;6(2):147–53.
pubmed: 25770253
pmcid: 4352173
doi: 10.3945/an.114.007526
Bakke AM, Wood J, Salt C, Allaway D, Gilham M, Kuhlman G, et al. Responses in randomised groups of healthy, adult Labrador retrievers fed grain-free diets with high legume inclusion for 30 days display commonalities with dogs with suspected dilated cardiomyopathy. BMC Vet Res. 2022;18(1):1–17.
de Oliveira Matheus LF, Risolia LW, Ernandes MC, de Souza JM, Oba PM, Vendramini THA, et al. Effects of Saccharomyces cerevisiae cell wall addition on feed digestibility, fecal fermentation and microbiota and immunological parameters in adult cats. BMC Vet Res. 2021;17(1):1–10.
doi: 10.1186/s12917-021-03049-8
Kim B, Lindemann M, editors. A spreadsheet method for experimental animal allotment. Journal of Animal Science; 2007: AMER SOC ANIMAL SCIENCE 1111 NORTH DUNLAP AVE, SAVOY, IL 61874 USA.
Kang C-W, Park M, Lee H-J. Mulberry (Morus alba L.) Leaf Extract and 1-Deoxynojirimycin improve skeletal muscle insulin resistance via the activation of IRS-1/PI3K/Akt pathway in db/db mice. Life. 2022;12(10):1630.
pubmed: 36295064
pmcid: 9604886
doi: 10.3390/life12101630
Chen S, Zhou Y, Chen Y, Gu J. Fastp: an ultra-fast all-in-one FASTQ preprocessor. Bioinformatics. 2018;34(17):i884–90.
pubmed: 30423086
pmcid: 6129281
doi: 10.1093/bioinformatics/bty560
Kim D, Paggi JM, Park C, Bennett C, Salzberg SL. Graph-based genome alignment and genotyping with HISAT2 and HISAT-genotype. Nat Biotechnol. 2019;37(8):907–15.
pubmed: 31375807
pmcid: 7605509
doi: 10.1038/s41587-019-0201-4
Pertea M, Kim D, Pertea GM, Leek JT, Salzberg SL. Transcript-level expression analysis of RNA-seq experiments with HISAT, StringTie and Ballgown. Nat Protoc. 2016;11(9):1650–67.
pubmed: 27560171
pmcid: 5032908
doi: 10.1038/nprot.2016.095
Ge SX, Son EW, Yao R. iDEP: an integrated web application for differential expression and pathway analysis of RNA-Seq data. BMC Bioinformatics. 2018;19(1):534.
pubmed: 30567491
pmcid: 6299935
doi: 10.1186/s12859-018-2486-6
Mi H, Muruganujan A, Ebert D, Huang X, Thomas PD. PANTHER version 14: more genomes, a new PANTHER GO-slim and improvements in enrichment analysis tools. Nucleic Acids Res. 2019;47(D1):D419–26.
pubmed: 30407594
doi: 10.1093/nar/gky1038
Heberle H, Meirelles GV, da Silva FR, Telles GP, Minghim R. InteractiVenn: a web-based tool for the analysis of sets through Venn diagrams. BMC Bioinformatics. 2015;16:1–7.
doi: 10.1186/s12859-015-0611-3
Estaki M, Jiang L, Bokulich NA, McDonald D, González A, Kosciolek T, et al. Curr Protocols Bioinf. 2020;70(1):e100. QIIME 2 Enables Comprehensive End-to-End Analysis of Diverse Microbiome Data and Comparative Studies with Publicly Available Data.
Callahan BJ, McMurdie PJ, Rosen MJ, Han AW, Johnson AJA, Holmes SP. DADA2: high-resolution sample inference from Illumina amplicon data. Nat Methods. 2016;13(7):581–3.
pubmed: 27214047
pmcid: 4927377
doi: 10.1038/nmeth.3869
Katoh K, Kuma K, Toh H, Miyata T. MAFFT version 5: improvement in accuracy of multiple sequence alignment. Nucleic Acids Res. 2005;33(2):511–8.
pubmed: 15661851
pmcid: 548345
doi: 10.1093/nar/gki198
Price MN, Dehal PS, Arkin AP. FastTree: Computing large minimum evolution trees with profiles instead of a Distance Matrix. Mol Biol Evol. 2009;26(7):1641–50.
pubmed: 19377059
pmcid: 2693737
doi: 10.1093/molbev/msp077
McDonald D, Price MN, Goodrich J, Nawrocki EP, DeSantis TZ, Probst A, et al. An improved Greengenes taxonomy with explicit ranks for ecological and evolutionary analyses of bacteria and archaea. ISME J. 2012;6(3):610–8.
pubmed: 22134646
doi: 10.1038/ismej.2011.139
Ondov BD, Bergman NH, Phillippy AM. Interactive metagenomic visualization in a web browser. BMC Bioinformatics. 2011;12(1):385.
pubmed: 21961884
pmcid: 3190407
doi: 10.1186/1471-2105-12-385
Segata N, Izard J, Waldron L, Gevers D, Miropolsky L, Garrett WS, et al. Metagenomic biomarker discovery and explanation. Genome Biol. 2011;12(6):R60.
pubmed: 21702898
pmcid: 3218848
doi: 10.1186/gb-2011-12-6-r60
Douglas GM, Maffei VJ, Zaneveld JR, Yurgel SN, Brown JR, Taylor CM, et al. PICRUSt2 for prediction of metagenome functions. Nat Biotechnol. 2020;38(6):685–8.
pubmed: 32483366
pmcid: 7365738
doi: 10.1038/s41587-020-0548-6
Gloor G. ALDEx2: ANOVA-Like Differential expression tool for compositional data. ALDEX Man Modular. 2015;20:1–11.