A Scoping Review of Gut Microbiome and Bifidobacterium Research in Zimbabwe: Implications for Future Studies

Figures & data

Figure 1 Prisma Flow Diagram for Scoping Reviews.

Notes: Adapted from Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021; 372:n71.²³

Table 1 Showing Results of the Systematic Literature Search; Fourteen Original Research Papers Were Retrieved.^24–37

Author, Year, Study Name, if Applicable	Participants N, Median Age (IQR) or Mean (SD) or Range	Study Design, % Female, and Participants and Site Description, Gene Profiling Method(s) and Other Lab Tests	Reported	General Findings	Specific Findings and Shortcomings
Gough et al, 2015, The Sanitation Hygiene Infant Nutrition Efficacy (SHINE) Trial Protocol^Citation24	N = 5280 women recruited, and 3791 live-born children were assessed (Mother–baby pairs).	Trial in rural area without specified sex distribution for infants, participants randomized to improved water, sanitation, and hygiene (WASH), and improved infant and young child feeding (IYCF), Shotgun metagenomics sequencing.	SHINE trial tested the independent and combined effects of improving infant diet and household WASH on length-for-age Z-score and hemoglobin (primary outcomes) at 18 months of age.	Secondarily tested the gut microbiome composition of mothers and babies in various publications on gut microbiome.^Citation24,Citation25,Citation28	N/A
Gough et al, 2021, The SHINE Trial Sub-study^Citation25	N=207, Mothers Mean ages: 31.2 (5.9) for those living with HIV, 27.2 years (6.7) for those without HIV.	Cross-sectional sub-study in a trial, 100% of them female. Participants being rural-based mothers and HIV-exposed and unexposed infants, Shotgun metagenomics sequencing.	Relationship between mothers’ microbiome and infants’ gestational age, birth weight, or neonatal growth.	Maternal fecal microbiome enriched for metabolizers of resistant-starch, including Ruminococcus bromii and Faecalibacterium prausnitizii, plus Prevotella copri abundant in populations feeding on high fibre diets.	Few Bacteroides indicating meat deficiency, resistant-starch degraders, were an important contributor to birth weight and neonatal growth, and to a lesser extent gestational age. A large proportion of DNA was unknown or unidentifiable.
Robertson et al, 2021, The SHINE trial Sub-study^Citation26	N=158, infants Median age = 43 days (35.0–68.0).	Cross-sectional sub-study of infants, from a rural trial, 43.6% female, within 30 days of an oral rotavirus vaccine (RVV), Shotgun metagenomics sequencing and anti-rotavirus IgA.	Stool metagenomes and their association with RVV immunogenicity.	RVV was poorly immunogenic, no association between gut microbiome and RVV seroconversion. However, maternal recall for some metadata led to low-quality data.	Bifidobacterium longum most abundant species, followed by Escherichia coli, B. bifidum, and B. pseudocatenulatum among others. Cross-sectional study design has inherent flaw of not distinguishing momentary changes from enduring ones in the gut microbiota.
Robertson et al, 2023, The SHINE Trial Sub-study^Citation27	N=335 infants, Age range = 1–18 months.	Cohort sub-study in a trial, infants, 43.9% female, from rural area, 1/3 of mothers are living with HIV, Shotgun metagenomics sequencing and nutritional status.	Analyzed gut microbiome of infants in a trial of improved WASH and IYCF.	Bifidobacteria, E. coli, and Bacteroides fragilis species most abundant <12 months of age.	Bifidobacterium longum predominant species up to 12 months of age. Maternal HIV status associated with reduced abundance of Bifidobacterium, and over-maturity, and over-diversification of the early-life gut microbiome in the uninfected children.
Smith et al, 2021, The CHAIN Trial Protocol^Citation28	N=192, Infants aged between 5 and 6 months.	Trial with infants, sex unspecified, from Shurugwi district, in rural Zimbabwe, Unspecified gut microbiome methods.	Infant and young child feeding (IYCF) and gut microbial composition.	Not yet published.	N/A
Flygel et al, 2020, The BREATHE Trial Sub-study^Citation29	N=177 children living with HIV and 103 HIV-uninfected controls, aged 6–16 years.	Cross-sectional sub-study in a trial of children, 47% females, from urban Harare, 16S rRNA (V4 hypervariable region) gene sequencing.	HIV, ART, and gut microbial composition.	Children living with HIV (CLWH) had significantly lower alpha-diversity and higher beta-diversity. Prolonged ART-treatment (≥10 years) associated with a richer gut microbiota by alpha diversity.	Enriched levels of Corynebacterium, Finegoldia, and Anaerococcus in CLWH and enrichment of Enterobacteriaceae in participants with low CD4+ counts.
Osakunor et al, 2020^Citation30	N=113 preschoolers, 1–5 years, 3.7 ± 1.1 years.	Cross-sectional study of 49.6% females, made up of children from a rural pre-school, Shotgun metagenomics sequencing.	Structure and diversity of the gut microbiome (bacteria, fungi) and resistome.	Infection with S. haematobium associated with alterations in the gut microbial but not with AMR gene abundance and diversity.	The most abundant bacteria phyla in decreasing order were Bacteroidota (previously Bacteroidetes), Faecalibacterium, Clostridium, and Proteobacteria
Kay et al, 2015^Citation31	N=139 children aged six months to 13 years old.	Cohort study, of children (50.9% female), from rural area with a high burden of S. haematobium (prevalence=27% in study participants), 16S rRNA (V3-V4 hypervariable region) gene sequencing.	Diversity and abundance of different gut bacteria by age, sex, infection with helminths parasites causing schistosomiasis and exposure to anti-helminthic praziquantel.	Some OTUs including Bacteroides and Helicobacter were more abundant in children ≤1 year old compared to older children.	Pre- and post-treatment the most abundant phyla were Bacteroidetes, Firmicutes, and Proteobacteria. Gut microbiome differed in schistosome-infected vs uninfected children.
Pfavayi et al, 2021^Citation32	N=116 preschoolers (≤5 years old.	Cross-sectional study of rural-based children, 50.9% females, Shotgun metagenomics sequencing.	Gut mycobiome and related it to fungal sensitization and sero-reactivity.	Mycobiome was <1% of the gut microbiome. Protomyces was most abundant.	Schistosoma haematobium had an effect on fungal genera. All produced Abs to the fungi.
Katsidzira et al, 2019^Citation33	N=20 adults, >50 years of age.	Cross-sectional study, 50% females, equal numbers of urban and rural adult participants, 16S rRNA whole gene sequencing.	Microbiota of urban and rural Zimbabweans, with focus on colorectal cancer.	There were differences in the relative abundance of a few genera.	No difference in the abundance of Fusobacteria, which has been associated with tumor formation in the colon. Some differences in Streptococcus bovis and Oscillospira guilliermondii between urban and rural participants.
Bourke et al, 2019, The ARROW Trial Sub-study^Citation34	N=140 stool samples from children, age unspecified, from Zimbabwe.	Cross-sectional sub-study in a trial, Children randomized to continue versus stop cotrimoxazole, Shotgun metagenomics sequencing for 20 VGS-positive samples.	Association of cotrimoxazole and the gut microbiome and biomarkers of intestinal inflammation.	Global microbiome composition was no different, but viridans group Streptococci (VGS) were lower among children continuing cotrimoxazole.	20 samples were positive for at least one of the VGS. Six samples were from children continuing and 14 were from children stopping cotrimoxazole. Individual VGS were present less often from children continuing cotrimoxazole.
Gough et al (2020), The ARROW Trial Sub-study^Citation35	N=20 children, age unspecified, from Zimbabwe.	Cross-sectional sub-study in a trial. Stool from six children who continued and fourteen from children who stopped cotrimoxazole and were positive for VGS.		S. salivarius strains in children living with HIV who are on ART who continued cotrimoxazole use are no different from those who stopped.	S. salivarius strains are different from those of children from high-income countries.
Duri et al^Citation36	N=1200 pregnant women (50% living with HIV) and their babies	Protocol describing an observational cohort. Maternal urine, stool, plasma, cord blood, amniotic fluid, placenta and milk plus infant plasma, dried blood spot, and stool collected at enrolment and follow-up visits.	An assessment of the maternal and infant gut microbiome and other factors of HIV-exposed, uninfected infants’ adverse outcomes.	Some results are described in paper.
Chandiwana et al, 2023, UZ-CHS Birth Cohort Sub-study^Citation37	N=94 Mothers, Median age = 28 years (22.3–32.0)	Cross-sectional sub-study in a cohort, Participants are 100% female, ie pregnant women, from urban area, 16S rRNA gene sequencing (segments spanning V5 and V6 regions).	Association of microbiota taxa with HIV infection and disease progression	HIV associated with lower α- and β-diversity.	HIV associated with lower abundance of Bacteroides and Bifidobacterium.

Box 1 Question About Potential Benefit of Starch Degrading Microbiome

Could resistant starch degraders be an important metabolic target to improve birth weight and neonatal growth?

Box 2 Long-Range Sequencing Methods

Could long-read sequencing help to distinguish infant microbiome signatures of RVV seroconverters and non-seroconverters?

Box 3 Bifidobacterium pseudocatenulatum and Formula Milk in Infants from Zimbabwe

What could be the explanation for the presence of Bifidobacterium pseudocatenulatum in the exclusively breastfed infants, which is usually associated with bottle (formula)-fed infants?

Box 4 Microbiota Differences in HIV-Exposed Children

Are microbiota differences observed in HIV-exposed children due to altered maternal microbiota, transformed human milk oligosaccharides from the mothers, prophylactic antiretroviral drugs OR prophylactic antibiotics, which may influence the seeding and succession of the infants’ gut microbiome?

Box 5 Identity of Potential Microbes

As maternal HIV is associated with a lower abundance of Bacteroides and Bifidobacterium, are these two viable nutritional probiotics, in pregnancy?

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