The gut microbiome in konzo.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
10 09 2021
Historique:
received: 01 09 2020
accepted: 24 08 2021
entrez: 11 9 2021
pubmed: 12 9 2021
medline: 15 10 2021
Statut: epublish

Résumé

Konzo, a distinct upper motor neuron disease associated with a cyanogenic diet and chronic malnutrition, predominately affects children and women of childbearing age in sub-Saharan Africa. While the exact biological mechanisms that cause this disease have largely remained elusive, host-genetics and environmental components such as the gut microbiome have been implicated. Using a large study population of 180 individuals from the Democratic Republic of the Congo, where konzo is most frequent, we investigate how the structure of the gut microbiome varied across geographical contexts, as well as provide the first insight into the gut flora of children affected with this debilitating disease using shotgun metagenomic sequencing. Our findings indicate that the gut microbiome structure is highly variable depending on region of sampling, but most interestingly, we identify unique enrichments of bacterial species and functional pathways that potentially modulate the susceptibility of konzo in prone regions of the Congo.

Identifiants

pubmed: 34508085
doi: 10.1038/s41467-021-25694-1
pii: 10.1038/s41467-021-25694-1
pmc: PMC8433213
doi:

Substances chimiques

Nitriles 0
linamarin H3V9RP3WLO

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

5371

Subventions

Organisme : FIC NIH HHS
ID : D43 TW009343
Pays : United States
Organisme : NIEHS NIH HHS
ID : R01 ES019841
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM128716
Pays : United States

Commentaires et corrections

Type : CommentIn

Informations de copyright

© 2021. The Author(s).

Références

Brewster, R. et al. Surveying gut microbiome research in Africans: toward improved diversity and representation. Trends Microbiol. 27, 824–835 (2019).
pubmed: 31178123 pmcid: 6764420 doi: 10.1016/j.tim.2019.05.006
Tang, M. et al. Different gut microbial profiles in sub-Saharan African and South Asian women of childbearing age are primarily associated with dietary intakes. Front. Microbiol. 10, 1848 (2019).
pubmed: 31474951 pmcid: 6702451 doi: 10.3389/fmicb.2019.01848
Schnorr, S. L. et al. Gut microbiome of the Hadza hunter-gatherers. Nat. Commun. 5, 3654 (2014).
pubmed: 24736369 doi: 10.1038/ncomms4654
Morton, E. R. et al. Variation in rural African gut microbiota is strongly correlated with colonization by Entamoeba and subsistence. PLoS Genet. 11, e1005658 (2015).
pubmed: 26619199 pmcid: 4664238 doi: 10.1371/journal.pgen.1005658
Gomez, A. et al. Gut microbiome of coexisting BaAka Pygmies and Bantu reflects gradients of traditional subsistence patterns. Cell Rep. 14, 2142–2153 (2016).
pubmed: 26923597 doi: 10.1016/j.celrep.2016.02.013
Hansen, M. E. B. et al. Population structure of human gut bacteria in a diverse cohort from rural Tanzania and Botswana. Genome Biol. 20, 16 (2019).
pubmed: 30665461 pmcid: 6341659 doi: 10.1186/s13059-018-1616-9
De Filippo, C. et al. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc. Natl Acad. Sci. USA 107, 14691–14696 (2010).
pubmed: 20679230 pmcid: 2930426 doi: 10.1073/pnas.1005963107
Bonder, M. J. et al. The effect of host genetics on the gut microbiome. Nat. Genet. 48, 1407–1412 (2016).
pubmed: 27694959 doi: 10.1038/ng.3663
Goodrich, J. K. et al. Human genetics shape the gut microbiome. Cell 159, 789–799 (2014).
pubmed: 25417156 pmcid: 4255478 doi: 10.1016/j.cell.2014.09.053
Goodrich, J. K. et al. Genetic determinants of the gut microbiome in UK twins. Cell Host Microbe 19, 731–743 (2016).
pubmed: 27173935 pmcid: 4915943 doi: 10.1016/j.chom.2016.04.017
Xu, C., Zhu, H. & Qiu, P. Aging progression of human gut microbiota. BMC Microbiol. 19, 236 (2019).
pubmed: 31660868 pmcid: 6819604 doi: 10.1186/s12866-019-1616-2
Aleman, F. D. D. & Valenzano, D. R. Microbiome evolution during host aging. PLoS Pathog. 15, e1007727 (2019).
pubmed: 31344129 pmcid: 6657895 doi: 10.1371/journal.ppat.1007727
Singh, R. K. et al. Influence of diet on the gut microbiome and implications for human health. J. Transl. Med. 15, 73–73 (2017).
pubmed: 28388917 pmcid: 5385025 doi: 10.1186/s12967-017-1175-y
Frame, L. A., Costa, E. & Jackson, S. A. Current explorations of nutrition and the gut microbiome: a comprehensive evaluation of the review literature. Nutr. Rev. 78, 798–812 (2020).
pubmed: 32211860 doi: 10.1093/nutrit/nuz106
Ley, R. E. et al. Obesity alters gut microbial ecology. Proc. Natl Acad. Sci. USA 102, 11070–11075 (2005).
pubmed: 16033867 pmcid: 1176910 doi: 10.1073/pnas.0504978102
Qin, J. et al. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature 490, 55–60 (2012).
pubmed: 23023125 doi: 10.1038/nature11450
Wang, X. et al. Sodium oligomannate therapeutically remodels gut microbiota and suppresses gut bacterial amino acids-shaped neuroinflammation to inhibit Alzheimer’s disease progression. Cell Res. 29, 787–803 (2019).
pubmed: 31488882 pmcid: 6796854 doi: 10.1038/s41422-019-0216-x
Henke, M. T. et al. Ruminococcus gnavus, a member of the human gut microbiome associated with Crohn’s disease, produces an inflammatory polysaccharide. Proc. Natl Acad. Sci. USA 116, 12672–12677 (2019).
pubmed: 31182571 pmcid: 6601261 doi: 10.1073/pnas.1904099116
Zinöcker, M. K. & Lindseth, I. A. The Western diet-microbiome-host interaction and its role in metabolic disease. Nutrients 10, 365 (2018).
pmcid: 5872783 doi: 10.3390/nu10030365
Gupta, V. K., Paul, S. & Dutta, C. Geography, ethnicity or subsistence-specific variations in human microbiome composition and diversity. Front. Microbiol. 8, 1162–1162 (2017).
pubmed: 28690602 pmcid: 5481955 doi: 10.3389/fmicb.2017.01162
Tomova, A. et al. The effects of vegetarian and vegan diets on gut microbiota. Front. Nutr. 6, 47–47 (2019).
pubmed: 31058160 pmcid: 6478664 doi: 10.3389/fnut.2019.00047
Arumugam, M. et al. Enterotypes of the human gut microbiome. Nature 473, 174–180 (2011).
pubmed: 21508958 pmcid: 3728647 doi: 10.1038/nature09944
Martínez, I. et al. The gut microbiota of rural papua new guineans: composition, diversity patterns, and ecological processes. Cell Rep. 11, 527–538 (2015).
pubmed: 25892234 doi: 10.1016/j.celrep.2015.03.049
Kashala-Abotnes, E. et al. Konzo: a distinct neurological disease associated with food (cassava) cyanogenic poisoning. Brain Res. Bull. 145, 87–91 (2019).
pubmed: 29981837 doi: 10.1016/j.brainresbull.2018.07.001
Tshala-Katumbay, D. et al. Cassava food toxins, konzo disease, and neurodegeneration in sub-Sahara Africans. Neurology 80, 949–951 (2013).
pubmed: 23460617 pmcid: 3653209 doi: 10.1212/WNL.0b013e3182840b81
Zhu, L. et al. Potential mechanism of detoxification of cyanide compounds by gut microbiomes of bamboo-eating pandas. mSphere 3, e00229–18 (2018).
pubmed: 29898983 pmcid: 6001608 doi: 10.1128/mSphere.00229-18
Kohl, K. D. & Dearing, M. D. The woodrat gut microbiota as an experimental system for understanding microbial metabolism of dietary toxins. Front. Microbiol. 7, 1165–1165 (2016).
pubmed: 27516760 pmcid: 4963388 doi: 10.3389/fmicb.2016.01165
Kohl, K. D. et al. Gut microbes of mammalian herbivores facilitate intake of plant toxins. Ecol. Lett. 17, 1238–1246 (2014).
pubmed: 25040855 doi: 10.1111/ele.12329
Kashala-Abotnes, E. et al. Konzo: a distinct neurological disease associated with food (cassava) cyanogenic poisoning. Brain Res. Bull. 145, 87–91 (2018).
pubmed: 29981837 pmcid: 6626527 doi: 10.1016/j.brainresbull.2018.07.001
Kashala-Abotnes, E. et al. Dietary cyanogen exposure and early child neurodevelopment: an observational study from the Democratic Republic of Congo. PLoS ONE 13, e0193261 (2018).
pubmed: 29664942 pmcid: 5903613 doi: 10.1371/journal.pone.0193261
Okafor, N. & Ejiofor, M. A. N. The linamarase of Leuconostoc mesenteroides: production, isolation and some properties. J. Sci. Food Agric. 36, 669–678 (1985).
doi: 10.1002/jsfa.2740360807
Lei, V., Amoa-Awua, W. K. & Brimer, L. Degradation of cyanogenic glycosides by Lactobacillus plantarum strains from spontaneous cassava fermentation and other microorganisms. Int. J. Food Microbiol. 53, 169–184 (1999).
pubmed: 10634708 doi: 10.1016/S0168-1605(99)00156-7
Vasconcelos, A. T. et al. Detoxification of cassava during gari preparation. Int. J. Food Sci. Technol. 25, 198–203 (1990).
doi: 10.1111/j.1365-2621.1990.tb01074.x
Giraud, E., Gosselin, L. & Raimbault, M. Degradation of cassava linamarin by lactic acid bacteria. Biotechnol. Lett. 14, 593–598 (1992).
doi: 10.1007/BF01023947
Tshala-Katumbay, D. D. et al. Cyanide and the human brain: perspectives from a model of food (cassava) poisoning. Ann. N. Y Acad. Sci. 1378, 50–57 (2016).
pubmed: 27450775 pmcid: 5063682 doi: 10.1111/nyas.13159
Senghor, B. et al. Gut microbiota diversity according to dietary habits and geographical provenance. Hum. Microb. J. 7-8, 1–9 (2018).
doi: 10.1016/j.humic.2018.01.001
Ayeni, F. A. et al. Infant and adult gut microbiome and metabolome in rural Bassa and urban settlers from Nigeria. Cell Rep. 23, 3056–3067 (2018).
pubmed: 29874590 doi: 10.1016/j.celrep.2018.05.018
Jha, A. R. et al. Gut microbiome transition across a lifestyle gradient in Himalaya. PLoS Biol. 16, e2005396 (2018).
pubmed: 30439937 pmcid: 6237292 doi: 10.1371/journal.pbio.2005396
Howlett, W. P. et al. Konzo, an epidemic upper motor neuron disease studied in Tanzania. Brain 113, 223–235 (1990).
pubmed: 2302534 doi: 10.1093/brain/113.1.223
Boivin, M. J. et al. Neuropsychological effects of konzo: a neuromotor disease associated with poorly processed cassava. Pediatrics 131, e1231–e1239 (2013).
pubmed: 23530166 pmcid: 3608487 doi: 10.1542/peds.2012-3011
Pessione, E. Lactic acid bacteria contribution to gut microbiota complexity: lights and shadows. Front. Cell. Infect. Microbiol. 2, 86 (2012).
pubmed: 22919677 pmcid: 3417654 doi: 10.3389/fcimb.2012.00086
Michlmayr, H. & Kneifel, W. β-Glucosidase activities of lactic acid bacteria: mechanisms, impact on fermented food and human health. FEMS Microbiol. Lett. 352, 1–10 (2014).
pubmed: 24330034 doi: 10.1111/1574-6968.12348
Majak, W. & Cheng, K.-J. Cyanogenesis in bovine rumen fluid and pure cultures of rumen bacteria. J. Anim. Sci. 59, 784–790 (1984).
doi: 10.2527/jas1984.593784x
Majak, W. & Cheng, K. J. Hydrolysis of the cyanogenic glycosides amygdalin, prunasin and linamarin by ruminal microorganisms. Can. J. Anim. Sci. 67, 1133–1137 (1987).
doi: 10.4141/cjas87-120
Cressey, P. & Reeve, J. Metabolism of cyanogenic glycosides: a review. Food Chem. Toxicol. 125, 225–232 (2019).
pubmed: 30615957 doi: 10.1016/j.fct.2019.01.002
Jaswal, V., Palanivelu, J. & Ramalingam, C. Effects of the Gut microbiota on Amygdalin and its use as an anti-cancer therapy: substantial review on the key components involved in altering dose efficacy and toxicity. Biochem. Biophys. Rep. 14, 125–132 (2018).
pubmed: 29872744 pmcid: 5986699
Cliff, J. et al. Konzo and continuing cyanide intoxication from cassava in Mozambique. Food Chem. Toxicol. 49, 631–635 (2011).
pubmed: 20654676 doi: 10.1016/j.fct.2010.06.056
Organization, W. H. WHO Konzo, a distinct type of upper motor neuron disease. Wkly. Epidemol. Rec. 30, 225–232 (1996).
Wood, D. E. & Salzberg, S. L. Kraken: ultrafast metagenomic sequence classification using exact alignments. Genome Biol. 15, R46 (2014).
pubmed: 24580807 pmcid: 4053813 doi: 10.1186/gb-2014-15-3-r46
Wood, D. E., Lu, J. & Langmead, B. Improved metagenomic analysis with Kraken 2. Genome Biol. 20, 257 (2019).
pubmed: 31779668 pmcid: 6883579 doi: 10.1186/s13059-019-1891-0
Lu, J. et al. Bracken: estimating species abundance in metagenomics data. PeerJ Computer Sci. 3, e104 (2017).
doi: 10.7717/peerj-cs.104
Breitwieser, F. P. & Salzberg, S. L. Pavian: interactive analysis of metagenomics data for microbiome studies and pathogen identification. Bioinformatics 36, 1303–1304 (2020).
pubmed: 31553437 doi: 10.1093/bioinformatics/btz715
McMurdie, P. J. & Holmes, S. phyloseq: An R package for reproducible interactive analysis and graphics of microbiome census data. PLoS ONE 8, e61217 (2013).
pubmed: 23630581 pmcid: 3632530 doi: 10.1371/journal.pone.0061217
Chen, S. et al. fastp: an ultra-fast all-in-one FASTQ preprocessor. Bioinformatics 34, i884–i890 (2018).
pubmed: 30423086 pmcid: 6129281 doi: 10.1093/bioinformatics/bty560
Kanehisa, M. et al. KEGG as a reference resource for gene and protein annotation. Nucleic Acids Res. 44, D457–D462 (2016).
pubmed: 26476454 doi: 10.1093/nar/gkv1070
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
Fernandes, A. D. et al. ANOVA-like differential expression (ALDEx) analysis for mixed population RNA-Seq. PLoS ONE 8, e67019 (2013).
pubmed: 23843979 pmcid: 3699591 doi: 10.1371/journal.pone.0067019
Fernandes, A. D. et al. Unifying the analysis of high-throughput sequencing datasets: characterizing RNA-seq, 16S rRNA gene sequencing and selective growth experiments by compositional data analysis. Microbiome 2, 15 (2014).
pubmed: 24910773 pmcid: 4030730 doi: 10.1186/2049-2618-2-15

Auteurs

Matthew S Bramble (MS)

Center for Genetic Medicine Research, Children's Research Institute, Children's National Hospital, Washington, DC, USA.

Neerja Vashist (N)

Center for Genetic Medicine Research, Children's Research Institute, Children's National Hospital, Washington, DC, USA.
Department of Genomics and Precision Medicine, George Washington University School of Medicine and Health Sciences, Washington, DC, USA.

Arthur Ko (A)

Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.

Sambhawa Priya (S)

Departments of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN, USA.

Céleste Musasa (C)

Center for Genetic Medicine Research, Children's Research Institute, Children's National Hospital, Washington, DC, USA.

Alban Mathieu (A)

Computational Biology Laboratory, CHU de Québec - Université Laval Research Center, Québec City, QC, Canada.

D' Andre Spencer (A)

Center for Genetic Medicine Research, Children's Research Institute, Children's National Hospital, Washington, DC, USA.

Michel Lupamba Kasendue (M)

Institut National de Recherche Biomédicale (INRB), Kinshasa, DR, Congo.

Patrick Mamona Dilufwasayo (P)

Center for Genetic Medicine Research, Children's Research Institute, Children's National Hospital, Washington, DC, USA.
Institut National de Recherche Biomédicale (INRB), Kinshasa, DR, Congo.

Kevin Karume (K)

Center for Genetic Medicine Research, Children's Research Institute, Children's National Hospital, Washington, DC, USA.
Institut National de Recherche Biomédicale (INRB), Kinshasa, DR, Congo.

Joanna Nsibu (J)

Institut National de Recherche Biomédicale (INRB), Kinshasa, DR, Congo.

Hans Manya (H)

Center for Genetic Medicine Research, Children's Research Institute, Children's National Hospital, Washington, DC, USA.
Institut National de Recherche Biomédicale (INRB), Kinshasa, DR, Congo.

Mary N A Uy (MNA)

Center for Genetic Medicine Research, Children's Research Institute, Children's National Hospital, Washington, DC, USA.
College of Medicine, University of the Philippines, Manila, Manila, Philippines.

Brian Colwell (B)

School of Public Health, Texas A&M University, College Station, TX, USA.

Michael Boivin (M)

Department of Psychiatry and Neurology & Ophthalmology, Michigan State University, East Lansing, MI, USA.

J P Banae Mayambu (JPB)

Ministry of Health National Program on Nutrition (PRONANUT), Kinshasa, DR, Congo.

Daniel Okitundu (D)

Centre Neuro-Psychopathologique (CNPP), University of Kinshasa, Kinshasa, Congo.

Arnaud Droit (A)

Computational Biology Laboratory, CHU de Québec - Université Laval Research Center, Québec City, QC, Canada.

Dieudonné Mumba Ngoyi (D)

Institut National de Recherche Biomédicale (INRB), Kinshasa, DR, Congo.
Department of Tropical Medicine, University of Kinshasa, Kinshasa, DR, Congo.

Ran Blekhman (R)

Departments of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN, USA.

Desire Tshala-Katumbay (D)

Institut National de Recherche Biomédicale (INRB), Kinshasa, DR, Congo. tshalad@ohsu.edu.
Department of Neurology and School of Public Health, Oregon Health & Science University, Portland, OR, USA. tshalad@ohsu.edu.

Eric Vilain (E)

Center for Genetic Medicine Research, Children's Research Institute, Children's National Hospital, Washington, DC, USA. evilain@CNMC.org.
Department of Genomics and Precision Medicine, George Washington University School of Medicine and Health Sciences, Washington, DC, USA. evilain@CNMC.org.
International Research Laboratory of Epigenetics, Data, Politics, Centre National de la Recherche Scientifique, Washington, DC, USA. evilain@CNMC.org.

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