Table 1 Summary of the African Human Gut Microbiome studies characteristics

Algeria, Mali, Senegal, Amazonian French Guiana, France, French Polynesia, Saudi Arabia

Obesity

Stool

16S rRNA, V3–V4 regions, Illumina MiSeq

France, French Polynesia, Mali, Saudi Arabia, Senegal

French Government through the Agence Nationale pour la Recherche (ANR), including the “Programme d’Investissement d’Avenir” under the reference Méditerranée Infection, Région Provence Alpes Côte d’Azur and European funding FEDER PRIMMI (Fonds Européen de Développement Régional - Plateforme de Recherche et d’Innovation Mutualisées Méditerranée Infection)

Case-control

92

High salt levels are associated with alteration of the gut microbial ecosystem and halophilic microbiota, as discovered during this study. Further studies should clarify if the gut microbiota alterations associated with high salt levels and the human halophilic microbiota could be causally related to human disease, such as obesity.

[60]

Botswana, Tanzania, USA

None

Stool

16S rRNA, V1–V2 regions, Illumina MiSeq

Botswana, Finland, Tanzania, UK, USA

Lewis and Clark Fund, University of Pennsylvania, Leakey Foundation, NIH, National Science Foundation

Cross-sectional

114

Across the cohort, similarity in bacterial presence/absence compositions between people increases with both geographic proximity and genetic relatedness, while abundance weighted bacterial composition varies more significantly with geographic proximity than with genetic relatedness.

[48]

Burkina Faso

Diarrhea

Stool

Viral shotgun metagenomic sequencing, 454 pyrosequencing

Burkina Faso, Chile, USA, Vietnam

NIH, Blood Systems Research Institute (USA)

Cross-sectional

98

A potential new genus in the Parvoviridae family was genetically characterized, and a PCR survey showed a prevalence of 4% among the rotavirus antigen-negative cases of childhood diarrhea.

[61]

Burkina Faso

None

Rectal swabs

16S rRNA, V3–V4 regions, Illumina

Burkina Faso, Germany, Niger, South Africa, USA

Research to Prevent Blindness, NIH

Randomized clinical trial

62

We found no evidence of an indirect effect of antibiotic use in cohabiting children.

[62]

Burkina Faso, Italy

None

Stool

16S rRNA, V5–V6 regions, 454 pyrosequencing

Belgium, Italy

Ministero dell'Universita, e della Ricerca (Italy), Ente Cassa di Risparmio di Firenze, Meyer's Children Hospital

Cross-sectional

15

It is important to sample and preserve microbial biodiversity from regions where effects of globalization on diet are less profound.

[63]

Burkina Faso

None

Rectal swabs

16S rRNA, V3–V4 regions, Illumina

Burkina Faso, Germany, South Africa, USA

Research to Prevent Blindness, NIH

Randomized clinical trial

115

Azithromycin affects the composition of the pediatric intestinal microbiome. The effect of amoxicillin and cotrimoxazole on microbiome composition was less clear.

[64]

Cameroon

None

Stool

Shotgun metagenomics, Illumina HiSeq

France

ANR MICROREGAL, Centre National de la Recherche Scientifique (LS), Institut Pasteur of Lille

Cross-sectional

57

Our study corroborates and expands prevalence results previously obtained for Blastocystis sp. and provides novel data for Entamoeba spp. and several other protozoan genera. Furthermore, it indicates that multiple protozoa are common residents of the healthy human gut worldwide.

[65]

Cameroon

None

Stool

16S rRNA, V5–V6 regions, Illumina MiSeq

France, USA

Howard Hughes Medical Institute, French National Agency for Research

Cross-sectional

64

Results show that gut communities vary significantly with subsistence mode, notably with some taxa previously shown to be enriched in other hunter-gatherer groups (Tanzania and Peru) also discriminating hunter-gatherers from neighboring farming or fishing populations in Cameroon.

[66]

Cameroon

Diarrhea

Stool

Viral shotgun metagenomics, Illumina NextSeq

Belgium, Cameroon

KU Leuven grant

Case-control

221

This study showed a huge diversity of highly divergent novel phages, thereby expanding the existing phageome considerably. Further screening of bat viruses in humans or vice versa will elucidate the epidemiological potential threats of animal viruses to human health.

[67]

Central African Republic, Madagascar

Stunted childhood growth

Gastric, duodenal, and stool

16S rRNA, V4 region, Illumina

Canada, Central African Republic, France, Madagascar

Total Foundation, Institut Pasteur, Pasteur Foundation Switzerland, Nutricia Research Foundation

Case-control

404

Our data suggest that stunting is associated with a microbiome “decompartmentalization” of the gastrointestinal tract characterized by an increased presence of oropharyngeal bacteria from the stomach to the colon, hence challenging the current view of stunting arising solely as a consequence of small intestine overstimulation through recurrent infections by enteric pathogens.

[68]

Central African Republic

None

Stool

16S rRNA, V1–V3 regions, 454 pyrosequencing

Central African Republic, USA, Czech Republic

NSF grant, Czech Science Foundation, University of Minnesota College of Biological Sciences, European Social Fund, Czech Republic Government, Central European Institute of Technology, the European Regional Development Fund, the Institute of Vertebrate Biology, Academy of Sciences of the Czech Republic

Cross-sectional

57

The results demonstrate gradients of traditional subsistence patterns in two neighboring African groups and highlight the adaptability of the microbiome in response to host ecology.

[69]

Central African Republic

None

Stool

16S rRNA, V1–V3 regions, 454 pyrosequencing

Austria, Central African Republic, Czech Republic, USA

European Social Fund and state budget of the Czech Republic, the U.S. National Science Foundation, Ministry of Education, Youth and Sports of The Czech Republic

Cross-sectional

57

The expanded comparative approach presented here indicates that subsistence patterns, such as those exhibited by contemporary hunter-gatherers or traditional agriculturalists, are associated with gut microbiome composition and diversity characterizing distantly related primates that exploit a broad-based diet.

[70]

Republic of the Congo

None

Stool

16S rRNA, V4 region, Shotgun metagenomics, Illumina MiSeq

Republic of the Congo, USA

NIH

Cross-sectional

81

The microbiome of closely related host species may be molded by changes in diet and the degree of antibiotic exposure despite their geographic location.

[71]

Republic of the Congo, Gabon

None

Stool and meconium

16S rRNA, V3 region, Ion Torrent PGM

Gabon, France, Republic of the Congo

Centre National de la Recherche Scientifique, Centre International de Recherche Médicales de Franceville, Institut de Recherche pour le Développement, Laboratoire mixte international ZOFAC

Longitudinal

29

Improve our knowledge on the gut bacterial and viral communities of infants from two Sub-Saharan countries during their first month of life.

[72]

Côte d'Ivoire

Diarrhea

Stool

Shotgun metagenomic sequencing, Illumina MiSeq

Côte d'Ivoire, Germany, Switzerland

Armasuisse project ARAMIS, the European Union's Seventh Framework Programme

Cross-sectional

4

A metagenomic approach provides detailed information on the presence and diversity of pathogenic organisms in human stool samples.

[73]

Côte d’Ivoire

Schistosomiasis

Stool

16S rRNA, V3–V4 regions, Illumina MiSeq

Côte d’Ivoire, Switzerland

European Research Council

Case-control

34

Our study suggests that neither a S. mansoni infection nor praziquantel administration triggers a significant effect on the microbial composition and that a higher abundance of Fusobacterium spp., before treatment, is associated with higher efficacy of praziquantel in the treatment of S. mansoni infections.

[74]

Egypt

Hepatitis C virus

Stool

16S rRNA, V4 region, Illumina MiSeq

Egypt

Not funded by any public or private institution

Case-control

15

This study provides a first overview of major phyla and genera differentiating stage 4-HCV patients from healthy individuals and suggests possible microbiome remodeling in chronic hepatitis C, possibly shaped by bacterial translocation as well as the liver’s impaired role in digestion and protein synthesis.

[75]

Egypt

Pediatric cancer

Stool

16S rRNA, V3–V5 regions, Illumina MiSeq

Egypt

Zewail City for Science and Technology

Case-control

5

The study is a start to offer a different angle for personalized treatment progress for pediatric cancer patients, based on the microbial profile rather than following a constant roadmap for the treatment protocol.

[76]

Egypt

Obesity and diabetes

Stool

16S rRNA, V3–V4 regions, Illumina MiSeq

Egypt

Not funded by any funding agencies

Case-control

60

The health state of the adults in our study defined the composition of the gut microbiota. Moreover, obesity and diabetes were associated with remarkably enriched populations of Firmicutes and Bacteroidetes.

[77]

Egypt, USA

None

Stool

16S rRNA, V4 region and Shotgun metagenomic sequencing, Illumina MiSeq

Egypt, USA

NA

Cross-sectional

28

The differences in fecal microbiota structure and functions and metabolite profiles between Egyptian and US teenagers are consistent with the nutrient variation between Mediterranean and Western diets.

[78]

Ethiopia

None

Stool

Viral shotgun metagenomics, Illumina MiSeq

Ethiopia, USA

NIH, That Man May See and The Sara & Evan Williams Foundation, Research to Prevent Blindness, National Heart, Lung, and Blood Institute grant, Blood Systems Research Institute

Cluster randomized trial

269

We documented a difference in pediatric enteric viromes according to mBSFS-C stool consistency category, both in species richness and composition.

[79]

Ethiopia

None

Stool

Viral shotgun metagenomics, Illumina MiSeq

Ethiopia, USA

Blood Systems Research Institute, NIH, Sara & Evan Williams Foundation, Bernard Osher Foundation, That Man May See, the Harper Inglis Trust, Bodri Foundation, South Asia Research Fund, Research to Prevent Blindness, Carter Center Ethiopia

Cluster randomized trial

269

Mammalian enteric virome diversity was not reduced in children from villages with a new water well. This population-based sampling also provides a baseline of the enteric viruses present in Northern Ethiopia against which to compare future viromes.

[80]

Ethiopia, Kenya, The Gambia, Ghana, Peru, Spain, Sweden, USA

None

Stool

16S rRNA, V1–V3 regions, Illumina MiSeq

Canada, Ethiopia, The Gambia, Ghana, Kenya, Peru, Spain, Sweden, UK, USA

National Science Foundation, NIH

Cross-sectional

217

Our results indicated that household composition (represented by the number of cohabitating siblings and other household members) did not have a measurable impact on the bacterial diversity, evenness, or richness of the IFM. However, we observed that variation in household composition categories did correspond to differential relative abundances of specific taxa, namely Lactobacillus, Clostridium, Enterobacter, and Klebsiella.

[81]

The Gambia

None

Stool

16S rRNA, V4 region, Illumina MiSeq

UK, USA

NIH, the Peter J. Shields Endowed Chair in Dairy Food Science

Longitudinal

33

These results suggest that specific types and structures of human milk oligosaccharides (HMOs) are sensitive to environmental conditions, protective of morbidity, predictive of growth, and correlated with specific microbiota.

[82]

Ghana, USA

Obesity

Stool

16S rRNA, V4 region, Illumina HiSeq

Ghana, USA

NIH

Case-control

50

We demonstrate that the association between obesity resistance and increased predicted ecological connectivity and stability of the lean Ghanaian microbiota, as well as increased local SCFA receptor level, provides evidence of the importance of a robust gut ecologic network in obesity.

[83]

Kenya

Worm infestation

Stool

16S rRNA, V4 region, Illumina MiSeq

Kenya, UK, USA

NIH, Bill and Melinda Gates Foundation

Longitudinal, cross-sectional (case-control)

100

This study contributes to our understanding of how microbial communities differ between soil-transmitted helminths STH-infected and uninfected individuals; the next step will be to understand the impact of the identified differences on human health.

[84]

Kenya

None

Stool

16S rRNA, V3–V6 regions, 454 pyrosequencing

Kenya, South Africa, Switzerland, The Netherlands

Eunice Kennedy Shriver National Institute Of Child Health and Human Development, European Union’s Seventh Framework Programme

Double-blind randomized controlled trial

115

In this setting, provision of iron-containing MNPs to weaning infants adversely affects the gut microbiome, increasing pathogen abundance and causing intestinal inflammation.

[85]

Kenya

Acute febrile malaria

Stool

16S rRNA, V3–V4 regions, Illumina

Kenya, UK, USA

Wellcome Trust, University of Louisville, NIH

Longitudinal

10

In-depth bioinformatics analysis of stool bacteria has revealed for the first time that human malaria episode/artemether-lumefantrine treatment has minimal effects on gut microbiota in Kenyan infants.

[86]

Kenya

None

Stool

16S rRNA, V1, V2, and V3 regions, Illumina MiSeq

Kenya, USA

Bill and Melinda Gates Foundation

Cross-sectional

143

These results suggest that the household should be considered a unit. Livestock activities, health, and microbiome perturbations among an individual child may have implications for other children in the household.

[87]

Kenya

None

Vaginal swabs

cpn60 UT-based sequencing, 454 pyrosequencing

Canada, Kenya

NIH, Bill and Melinda Gates Foundation

Cross-sectional

44

Cpn60 UT is ideally suited to next-generation sequencing technologies for further investigation of microbial community dynamics and mucosal community underlying HIV resistance in this cohort.

[88]

Kenya

Anemia

Stool

16S rRNA, V3–V4 regions, Illumina MiSeq

Kenya, Switzerland, The Netherlands

ETH Global, the Sawiris Foundation for Social Development, ETH Zurich, DSM Nutritional Products

Double-blind randomized controlled trial

155

A micronutrient powder containing a low dose of highly bioavailable iron reduces anemia, and the addition of galacto-oligosaccharides mitigates most of the adverse effects of iron on the gut microbiome and morbidity in African infants.

[89]

Kenya

None

Stool

16S rRNA, V3–V4 regions, Illumina MiSeq

Kenya, The Netherlands, Switzerland

ETH global and the Sawiris Foundation for Social Development, DSM nutritional Products, Sight and life

Double-blind randomized controlled intervention trial

150

Human milk oligosaccharides profile may modulate the infant gut microbiota response to fortificant iron; compared to infants of secretor mothers, infants of non-secretor mothers may be more vulnerable to the adverse effect of iron but also benefit more from the co-provision of GOS.

[9]

Kenya

Diarrhea

Stool

16S rRNA, V3–V4 regions, Illumina MiSeq

Kenya, The Netherlands, Switzerland

ETH global and the Sawiris Foundation for Social Development, ETH Zurich, DSM nutritional Products, Sight and life

Double-blind randomized controlled intervention trial

28

Our findings need confirmation in a larger study but suggest that, in African infants, iron fortification modifies the response to broad-spectrum antibiotics: iron may reduce their efficacy against potential enteropathogens, particularly pathogenic E. coli, and may increase the risk for diarrhea.

[90]

Kenya, Mali, The Gambia, Bangladesh

Diarrhea

Stool

16S rRNA, V1-V2 region, 454 pyrosequencing

Bangladesh, Kenya, Mali, The Gambia, UK, USA

Bill and Melinda Gates Foundation, NIH, Wellcome Trust

Cross-sectional

786

The study demonstrates that the major differences in the microbiota between diarrheal and normal stools are quantitative differences in the proportions of the most prevalent taxa.

[91]

Kenya

None

Stool

16S rRNA, V4 region, Illumina MiSeq

Kenya, USA

International Atomic Energy Agency research, NIH, Colorado Clinical and Translational Sciences Institute

Double-blind, individually-randomized, controlled trial

33

Micronutrient powder fortification over three months in non- or mildly anemic Kenyan infants can potentially alter the gut microbiome. Consistent with previous research, the addition of iron to the MNP may adversely affect the colonization of potential beneficial microbes and attenuate the decrease of potential pathogens.

[92]

Liberia, Indonesia

Helminth infections

Stool

16S rRNA, V1-V3 region, Illumina MiSeq (Liberia), 454 pyrosequencing (Indonesia), Shotgun metagenomics, Illumina HiSeq

Indonesia, Liberia, The Netherlands, USA

NIH, Bill and Melinda Gates Foundation

Cross-sectional

98

These results provide a novel insight into the cross-kingdom interactions in the human gut ecosystem by unlocking the microbiome assemblages at taxonomic, genetic, and functional levels so that advances toward key mechanistic studies can be made.

[93]

Malawi

None

Stool

16S rRNA, V4 region, Illumina MiSeq

Finland, Malawi, Singapore, USA

Academy of Finland, Bill and Melinda Gates Foundation

Randomized control trial

213

Nutritional supplementation by lipid-based nutrient supplements or corn-soya blend for 12 months did not affect the gut microbiota in the rural Malawian context.

[94]

Malawi

Malnutrition

Stool

16S rRNA, V4 region

Finland, Malawi, Singapore, USA

Bill and Melinda Gates Foundation

Randomized, controlled, and partly blinded clinical trial

631

The results do not support the hypothesis that adverse environmental exposures are broadly associated with lower microbiota maturity and diversity but suggest that environmental exposures influence the abundance of several bacterial OTUs and genera and that low maternal education is associated with higher microbiota maturity and diversity.

[95]

Malawi

Childhood infections

Stool

16S rRNA, V4 region, Illumina MiSeq

Finland, Malawi, Singapore, USA

Bill and Melinda Gates Foundation

Prospective cohort

631

Our findings generally do not support the hypothesis that morbidity prevalence predicts a subsequent decrease in gut microbiota maturity or diversity in rural Malawian children. Certain morbidity symptoms may be predictive of microbiota maturity and diversity and relative abundances of several bacterial taxa. Furthermore, microbiota diversity and maturity may be associated with the subsequent incidence of fever.

[96]

Malawi

Gut inflammation

Stool

16S rRNA, V1–V3, V3–V5 regions, 454 pyrosequencing and Shotgun metagenomic sequencing, Illumina HiSeq

Australia, Malawi, USA

Flinders University, Bill and Melinda Gates Foundation, NIH

Longitudinal

18

The findings do not support the hypothesis that resistant starch reduced gut inflammation in rural Malawian children.

[97]

Malawi

Environmental enteric dysfunction

Stool

16S rRNA, V1–V2 regions, Illumina MiSeq

Malawi, USA

The Feed the Future Program, USAID, the Children’s Discovery Institute of Washington University, St. Louis Children’s Hospital

Cross-sectional

81

Bacterial diversity did not vary with the extent of environmental enteric dysfunction.

[98]

Malawi

Severe acute malnutrition

Stool

16S rRNA, V4 region, 18S rRNA (28S rRNA variable genetic region 2 and the internal transcribed spacers (transITS)), V4–V5 regions, Illumina MiSeq

Canada, Kenya, Malawi, The Netherlands, USA

Center for Global Child Health, SickKids Research Institute & Natural Sciences and Engineering Research Council of Canada

Cross-sectional

46

We suggest this novel two-amplicon-based strategy will prove an effective tool to deliver new insights into the role of eukaryotic microbiota in health and disease.

[99]

Malawi

Malnutrition

Stool

16S rRNA, V4 region, Illumina MiSeq and Shotgun metagenomic sequencing, 454 pyrosequencing

Colombia, Malawi, USA,

Bill and Melinda Gates Foundation, NIH

Case-control

40

The results revealed that apparently healthy twins in discordant pairs have viromes associated with, although not necessarily mediators of severe acute malnutrition.

[100]

Malawi

Kwashiorkor

Stool

16S rRNA, V4 region, Illumina and Shotgun metagenomic sequencing, 454 pyrosequencing

Malawi, UK, USA

Bill and Melinda Gates Foundation, NIH

Longitudinal

41

Results illustrate the value of using twins discordant for nutritional phenotypes to characterize the interrelationship between the functional development of the gut microbiome in children and their nutritional status.

[101]

Malawi, USA, Venezuela

None

Stool

16S rRNA, V4 region, Illumina HiSeq and Shotgun metagenomic sequencing, 454 pyrosequencing

Malawi, Puerto Rico, USA, Venezuela

NIH, St. Louis Children’s Discovery Institute, Howard Hughes Medical Institute, Crohn’s and Colitis Foundation of America, Bill and Melinda Gates Foundation

Cross-sectional

115

Pronounced differences in bacterial assemblages and functional gene repertoires were noted between US residents and those in Malawi and Venezuela. These distinctive features are evident in early infancy as well as adulthood. The findings underscore the need to consider the microbiome when evaluating human development, nutritional needs, physiological variations, and the impact of westernization.

[102]

Mali

Plasmodium falciparum infection

Stool

16S rRNA, V1–V3 regions, 454 pyrosequencing

Mali, USA

NIH

Cross-sectional

200

The findings underscore the diversity of gut microbiota across geographic regions and suggest that strategic modulation of gut microbiota composition could decrease the risk of P. Falciparum infection in malaria-endemic areas, potentially as an adjunct to partially effective malaria vaccines.

[103]

Mali

Blastocystis

Stool

16S rRNA, V3–V4 regions, Illumina MiSeq

France, Mali

The IHU-Mediterranean Infection Foundation, African Academy of Sciences, Wellcome Trust, UK government

Cross-sectional

296

Blastocystis colonization is significantly associated with a higher diversity of the gut bacterial communities in healthy children, while it is not associated with the presence of potentially pathogenic bacteria in the human gut.

[104]

Mali, Mozambique, India

Shigella infections

Stool

Shotgun metagenomics, Illumina HiSeq

India, Mali, Mozambique, Pakistan, USA

Bill and Melinda Gates Foundation, NIH, Fogarty International Center

Cross-sectional

18

Metagenomic sequencing indicates that Shigella/EIEC qPCR-positive samples are similar to those of Shigella culture-positive samples in Shigella sequence composition, thus supporting qPCR as an accurate method for detecting Shigella.

[105]

Mali

Pulmonary tuberculosis

Stool

Shotgun metagenomic sequencing, Illumina HiSeq

Mali, USA

NIH, Howard Hughes Medical Institute

Cross-sectional

10

Oral Urea Breath Test has significant limitations as a point of care diagnostic tool for pulmonary tuberculosis in a setting with endemic H. pylori infection.

[106]

Morocco

Colorectal cancer

Stool

16S rRNA, V1–V2 regions, Illumina MiSeq

Morocco, USA

NIH

Case-control

23

This suggests that involvement of the functional metagenomes detected in the study is similar and relevant in the carcinogenesis process, independent of the origin of the samples. Results from this study allowed identification of bacterial taxa relevant to the Moroccan population and encourages larger studies to facilitate population-directed therapeutic approaches.

[3]

Niger

None

Rectal swabs

16S rDNA, V3–V4 regions, Illumina

Niger, USA

Bill and Melinda Gates Foundation, Peierls Foundation, NIH, Research to Prevent Blindness

Double-blind randomized controlled trial

80

Oral administration of azithromycin definitively decreases the diversity of the gut microbiome of children in an antibiotic-naive community.

[107]

Niger

None

Rectal swabs and Stool

Shotgun metagenomics, Illumina HiSeq

Niger, USA

Bill and Melinda Gates Foundation, NIH, Research to Prevent Blindness Career Development Award, Research to Prevent Blindness

Double-masked, cluster randomized controlled clinical trial

300

Two mass azithromycin administrations, 6 months apart, in preschool children led to long-term alterations of the gut microbiome structure and community diversity. Here, long-term microbial alterations in the community did not imply disease but were associated with an improvement in childhood mortality.

[108]

Niger

None

Rectal swabs

Shotgun metagenomics, Illumina HiSeq

Niger, USA

Bill and Melinda Gates Foundation, the Peierls Foundation, Research to Prevent Blindness Career Development Award, Research to Prevent Blindness

Cluster randomized controlled trial

300

These results suggest that prolonged mass azithromycin distribution to reduce childhood mortality reduces certain gut bacteria, including known pathogens, while selecting for antibiotic resistance.

[109]

Niger

None

Rectal swabs

16S rRNA, V3–V4 regions, Illumina MiSeq

Niger, USA

Bill and Melinda Gates Foundation, Peierls Foundation, NIH, Research to Prevent Blindness

Cluster randomized clinical trial

80

Pooling microbiome samples before DNA amplification and metagenomics sequencing to estimate community-level diversity is a viable measure to consider in population-level association research studies.

[110]

Niger, Senegal

Kwashiorkor

Stool

16S rRNA, V3–V4 regions, Illumina MiSeq, and MALDI-TOF Culturomics

France, Mali, Niger, Senegal, UK

The Mediterranée Infection Foundation

Case-control

15

A complex of 12 species identified only in healthy children using culturomics and metagenomics were identified as probiotic candidates, providing a possible, defined, reproducible, safe, and convenient alternative to fecal transplantation to restore a healthy gut microbiota in malnourished children. Microbiotherapy based on selected strains has the potential to improve the current treatment of severe acute malnutrition and prevent relapse and death by reestablishing a healthy gut microbiota.

[111]

Nigeria

Type 2 diabetes

Stool

16S rRNA, V4 region, Illumina MiSeq

Nigeria, USA

NIH, the Intramural Research Program of the Center for Research on Genomics and Global Health with funding from NHGRI and NIDDK

Case-control

291

This first investigation of gut microbiome and diabetes in urban Africans shows that type 2 diabetes is associated with compositional changes in gut microbiota highlighting the possibility of developing strategies to improve glucose control by modifying bacterial composition in the gut.

[112]

Nigeria

None

Stool

16S rRNA, V4 region, Illumina MiSeq

Austria, Nigeria

Austrian Agency for International Mobility and Cooperation in Education, Science, and Research, Centre for International Cooperation and Mobility

Case-control

50

Significant differences in composition between both groups were likely due to differences in diet and lifestyle and exposure to pathogens. These results suggest that microbial diversity may not always be higher in non-industrialized societies than in westernized societies, as previously assumed.

[113]

Nigeria

None

Stool

16S rRNA, V3–V4 regions, Illumina MiSeq

Austria, Italy, Nigeria

Society for Applied Microbiology

Cross-sectional

48

Our findings stress the loss of ancient signatures along with urbanization and support distinct trajectories of development of the intestinal ecosystem in early life, depending on human subsistence.

[114]

Nigeria, Sudan, Azerbaijan, Jordan

Diabetes

Stool

16S rRNA, V4 region, Illumina MiSeq

Azerbaijan, Czech Republic, Jordan, Nigeria, Sudan

Ministry of Health of the Czech Republic

Case-control

83

Based on our results, some type of distortion of the gut bacteriome appears to be a global feature of type 1 diabetes, and our findings for four distant populations add new candidates to the existing list of bacteria. It remains to be established whether the observed associations are markers or causative factors.

[115]

Nigeria

HIV/AIDS

Rectal swabs

16S rRNA, V3–V4 regions, Illumina MiSeq

Nigeria, USA

Mpower, NIH, US Military HIV Research Program, CDC, Global AIDS program with IHVN

Cross-sectional

130

Untreated HIV infection does not significantly alter the rectal microbiota, whereas prior treatment is associated with a shift toward a more pathogenic pattern of microbiota.

[116]

Nigeria

Human papillomavirus and HIV

Rectal swabs

16S rRNA, V4 region, Illumina MiSeq

Nigeria, USA

National Cancer Institute, NIH, Henry M. Jackson Foundation for the Advancement of Military Medicine, U.S. Department of Defense, Fogarty Epidemiology Research Training for Public Health Impact in Nigeria program, the President’s Emergency Plan for AIDS Relief through a cooperative agreement between the Department of Health and Human Services/Centers for Disease Control and Prevention, Global AIDS Program, Institute for Human Virology-Nigeria

Cross-sectional

113

Further studies are needed to evaluate whether an anal microbial community enriched with members of the Fusobacteria phylum is associated with HIV-infected MSM who are virally suppressed and have a concurrent HPV-16.

[117]

Senegal

None

Stool

16S rRNA, V6 region, 454 pyrosequencing

France

European Research Council

Cross-sectional

1

There is evidence of the presence of mimiviruses and marseilleviruses in humans.

[118]

Senegal, France

None

Stool

16S rRNA, V6 region, 454 pyrosequencing

France, Senegal, USA

Centre National de la Recherche Scientifique, Institut de Recherche et Développement, Aix-Marseille Université

Cross-sectional

2

Microbial diversity in the human gut is substantially broader than predicted on the basis of genomic and metagenomic analyses.

[119]

South Africa

Respiratory, gastrointestinal, and other diseases

Stool

16S rRNA, V3–V4 regions, Illumina Miseq

Germany, South Africa

Institute for Food, Nutrition and Well-being and Genomics Research Institute, University of Pretoria

Case-control

34

This study provides preliminary evidence for the fecal microbiome-derived dysbiosis signature and pathobiome concept that may be observed in young children during illness.

[120]

South Africa

Atopic dermatitis

Stool

16S rRNA, V4 region, Illumina MiSeq

South Africa, USA

NIH, Brinson Foundation

Cross-sectional

38

No significant differences were observed in microbial diversity between the children with atopic dermatitis (AD) and the control children, and there were no differences in the relative abundance for any taxa between these 2 groups after adjusting for multiple comparisons.

[121]

South Africa, USA

Colorectal cancer

Stool

16S rRNA, V4 region, Illumina MiSeq

Germany, South Africa, UK, USA

NIH

Prospective cohort

21

The low-fiber, high-fat diet of Alaskan Native people and exposure to carcinogens derived from diet or environment are associated with a tumor-promoting colonic milieu as reflected by the high rates of adenomatous polyps in Alaska Native participants.

[122]

South Africa, USA

Colon cancer risk

Stool

16S rRNA, 454 pyrosequencing

South Africa, The Netherlands, USA

NIH

Cross-sectional

12

The results support the hypothesis that colon cancer risk is influenced by the balance between microbial production of health-promoting metabolites such as butyrate and potentially carcinogenic metabolites such as secondary bile acids.

[123]

South Africa

None

Stool

16S rRNA, V4 region, Illumina MiSeq

South Africa, USA

National Institute of Child Health and Human Development, National Institute of Environmental Health Sciences, National Science Foundation, University of Washington Center for AIDS Research, NIH, Harry Crossley Foundation, Suid-Afrikaanse Akademie vir Wetenskap en Kuns, US Agency for International Development

Prospective, longitudinal

155

These data suggest that non-exclusive breastfeeding alters the gut microbiota, increasing T-cell activation and, potentially, mucosal recruitment of HIV target cells. Study findings highlight a biologically plausible mechanistic explanation for the reduced post-natal HIV transmission observed in exclusively breastfed infants.

[124]

South Africa

None

Stool

16S rRNA, V4 region, Illumina MiSeq

South Africa, USA

H3Africa U01 award from NIH, the Wellcome Trust, Bill and Melinda Gates Foundation Global Health Grant, the National Research Foundation, and the Carnegie Corporation of New York, South African Medical Research Council

Cohort

197

The meconium from infants investigated in our study contained high proportions of the phylum Proteobacteria, in particular bacteria within the Enterobacteriaceae family.

[125]

Tanzania, Italy

None

Stool

Shotgun metagenomic sequencing

Germany, Italy, USA

Max Planck-Gessellschaft, Lincy Foundation

Cross-sectional

27

The results demonstrate how the functional specificity of the gut microbiota shows correlation to some environmental and lifestyle factors specific to the Hadza and urban Italians sampled in this study.

[32]

Tanzania, Italy

None

Stool

16S rDNA, V4 region, 454 pyrosequencing

Germany, Italy, Tanzania, UK, USA

Lincy Foundation, Max-Planck-Gesellschaft

Cross-sectional

27

The Hadza have higher levels of microbial richness and biodiversity than Italian urban controls.

[33]

Tanzania, USA

None

Stool

16S rRNA, V1–V3 and V3–V5 regions, Illumina MiSeq and Shotgun metagenomic sequencing, Illumina HiSeq

Canada, Tanzania, UK, USA

The Emch Family Foundation and Forrest & Frances Lattner Foundation, C&D Research Fund, NIH, Discovery Innovation Fund Awards

Longitudinal

188

The taxa within the Hadza that are the most seasonally volatile similarly differentiate industrialized and traditional populations. These data indicate that some dynamic lineages of microbes have decreased in prevalence and abundance in modernized populations.

[126]

Tanzania

Toxic blood metal levels

Stool

16S rRNA, V6 region, Ion Torrent PGM

Canada, Tanzania

Bill and Melinda Gates Foundation

Randomized open-label pilot study

104

The study demonstrated the potential value of long-term probiotic-based interventions to counter mercury and arsenic exposure in vulnerable populations.

[21]

Uganda

HIV/AIDS

Stool

16S rRNA, Illumina MiSeq

Uganda, USA

NIH, Harvard Center for AIDS Research

Case-control

122

Severe immunodeficiency is the likely mechanism leading to changes in the fecal microbiome.

[127]

Uganda

Malnutrition

Stool

16S rRNA, V3–V4 regions, Illumina MiSeq

Denmark, Uganda

Knud Højgaards Foundation, Oticon Foundation, Arvid Nilssons Foundation, Aase and Ejnar Danielsens Foundation, Brødrene Hartsmanns Foundation, Augustinus Foundation, Axel Muudfeldts Foundation, Torkild Steenbecks Legat, The Danish Free Research Council

Cross-sectional

87

The non-edematous SAM children have lower gut microbiota diversity compared to edematous SAM children; however, no clear compositional differences were identified.

[128]

Uganda

None

Stool

16S rRNA, V1–V2 regions, Illumina MiSeq

Uganda, UK

Wellcome, European Research Council Starting Grant

Cross-sectional

3

Stool collected in a fieldwork setting for comparative microbiome analyses should ideally be stored as consistently as possible using the same preservation method throughout.

[129]

Uganda

Malnutrition

Stool

16S rRNA

The Netherlands, Norway, South Africa, Uganda

The Throne Holst Foundation, University of Oslo, TNO’s Early Research Program “Personalized Health”

Two-armed, open-cluster, randomized education intervention

147

The maternal education intervention had positive effects on child development and growth at 3 years but did not alter gut microbiota composition. This intervention may be applicable in other low-resource settings.

[130]

Uganda

None

Stool

16S rRNA, V4–V5 regions, 454 pyrosequencing

Uganda, UK

UK Medical Research Council

Cross-sectional

21

The results show potential for the sharing of usually commensal bacterial taxa between humans and other animals.

[131]

Zimbabwe

HIV

Rectal swabs

16S rRNA, V4 region, Illumina MiSeq

Australia, Norway, South Africa, UK, Zimbabwe

Global Health and Vaccination Programme of the Medical Research Council of Norway, Northern Norway Regional Health Authority, NIH

Case-control

280

Human immunodeficiency virus-infected children have altered gut microbiota. Prolonged antiretroviral therapy may restore the richness of the microbiota closer to that of HIV-uninfected children.

[132]

Zimbabwe

HIV

Stool

Shotgun metagenomics

Canada, Uganda, UK, Zimbabwe

Wellcome Trust, Canadian Institutes of Health Research, Medical Research Council, European Union, MRC Clinical Trials Unit at UCL

Randomized control study

72

These data demonstrate that cotrimoxazole reduces systemic and intestinal inflammation both indirectly via antibiotic effects on the microbiome, and directly by blunting immune and epithelial cell activation. Synergy between these pathways may explain the clinical benefits of cotrimoxazole despite high antimicrobial resistance, providing further rationale for extending coverage among people living with HIV in sub-Saharan Africa.

[133]

Zimbabwe

Parasite infection

Stool

16S rRNA, V3–V4 regions, Illumina MiSeq

UK, Zimbabwe

WHO, Wellcome Trust, Thrasher Research Fund, Waiwick Medical School

Longitudinal

62

There are significant differences in the gut microbiome structure of infected vs. uninfected children and the differences were refractory to Praziquantel treatment.

[134]