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Mulyani AT, Khairinisa MA, Khatib A, Chaerunisaa AY. Understanding Stunting: Impact, Causes, and Strategy to Accelerate Stunting Reduction-A Narrative Review. Nutrients 2025; 17:1493. [PMID: 40362802 PMCID: PMC12073730 DOI: 10.3390/nu17091493] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2025] [Revised: 04/21/2025] [Accepted: 04/23/2025] [Indexed: 05/15/2025] Open
Abstract
Stunting is a major global health concern, particularly in low- and middle-income countries, due to its persistently high prevalence. It often originates from chronic malnutrition during the critical first 1000 days of life. Maternal and child nutrition are critical determinants of a child's growth and development. This article aimed to explore the impact, causes, and evidence-based strategies to accelerate the reduction of stunting incidence worldwide. This review was undertaken with sources from PubMed, Scopus, Google Scholar, Science Direct, and MEDLINE from October 2024 to January 2025. This review was undertaken with sources from PubMed, Scopus, Google Scholar, Science Direct, and MEDLINE from October 2024 to January 2025 using the keyword "Stunting", "Causes of stunting", "Stunting Impact", "Stunting Intervention", and "Stunting Prevention". The findings highlight the multifactorial causes of stunting, including maternal malnutrition, inadequate breastfeeding and complementary feeding, poor sanitation, and socioeconomic factors. Stunting is associated with impaired linear growth, cognitive deficits, gut dysbiosis, endocrine disruption, anemia, and increased risk of chronic diseases later in life. Addressing stunting demands multisectoral strategies focusing on maternal and child nutrition, infection prevention, improved WASH (Water, Sanitation, and Hygiene) practices, and socioeconomic support. The evidence presented may guide policy development and targeted interventions to prevent stunting and its long-term effects.
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Affiliation(s)
- Aisyah Tri Mulyani
- Magister Program, Faculty of Pharmacy, University of Padjadjaran, Jalan Raya Bandung Sumedang km 21 Jatinangor, Sumedang 45363, Indonesia;
| | - Miski Aghnia Khairinisa
- Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, University of Padjadjaran, Jalan Raya Bandung Sumedang km 21 Jatinangor, Sumedang 45363, Indonesia;
| | - Alfi Khatib
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, International Islamic University Malaysia (IIUM), Kuantan 25200, Pahang, Malaysia;
| | - Anis Yohana Chaerunisaa
- Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, University of Padjadjaran, Jalan Raya Bandung Sumedang km 21 Jatinangor, Sumedang 45363, Indonesia
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2
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Seco-Hidalgo V, Witney AA, Chico ME, Vaca M, Arevalo A, Schuyler AJ, Platts-Mills TAE, Ster IC, Cooper PJ. Rurality and relative poverty drive acquisition of a stable and diverse gut microbiome in early childhood in a non-industrialized setting. Sci Rep 2025; 15:5601. [PMID: 39955323 PMCID: PMC11830098 DOI: 10.1038/s41598-025-89224-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2024] [Accepted: 02/04/2025] [Indexed: 02/17/2025] Open
Abstract
There are limited longitudinal data from non-industrialized settings on patterns and determinants of gut bacterial microbiota development in early childhood. We analysed epidemiological data and stool samples collected from 60 children followed from early infancy to 5 years of age in a rural tropical district in coastal Ecuador. Data were collected longitudinally on a wide variety of individual, maternal, and household exposures. Extracted DNA from stool samples were analysed for bacterial microbiota using 16S rRNA gene sequencing. Both alpha and beta diversity indices suggested stable profiles towards 5 years of age. Greater alpha diversity and lower beta diversity were associated with factors typical of rural poverty including low household incomes, overcrowding, and greater agricultural and animal exposures. Consumption of unpasteurized milk was consistently associated with greater alpha diversity indices. Delivery method and antibiotic exposures during pregnancy and early childhood appeared to have limited effects on developmental trajectories of gut microbiota. Infants living in a non-industrialized setting in conditions of greater poverty and typically rural exposures appeared to acquire more rapidly a stable and diverse gut bacterial microbiome during childhood.
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Affiliation(s)
- Victor Seco-Hidalgo
- Institute of Infection and Immunity, St George's University of London, London, SW17 0RE, UK
| | - Adam A Witney
- Institute of Infection and Immunity, St George's University of London, London, SW17 0RE, UK
| | - Martha E Chico
- Fundación Ecuatoriana Para la Investigación en Salud, Quito, Ecuador
| | - Maritza Vaca
- Fundación Ecuatoriana Para la Investigación en Salud, Quito, Ecuador
| | - Andrea Arevalo
- Fundación Ecuatoriana Para la Investigación en Salud, Quito, Ecuador
| | - Alexander J Schuyler
- Division of Allergy & Clinical Immunology, University of Virginia, Charlottesville, VA, USA
| | | | - Irina Chis Ster
- Institute of Infection and Immunity, St George's University of London, London, SW17 0RE, UK
| | - Philip J Cooper
- Institute of Infection and Immunity, St George's University of London, London, SW17 0RE, UK.
- Escuela de Medicine, Universidad Internacional del Ecuador, Quito, Ecuador.
- Fundación Ecuatoriana Para la Investigación en Salud, Quito, Ecuador.
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Seco-Hidalgo V, Witney A, Chico ME, Vaca M, Arevalo A, Schuyler AJ, Platts-Mills TA, Ster IC, Cooper PJ. Rurality and relative poverty drive acquisition of a stable and diverse gut microbiome in early childhood in a non-industrialized setting. RESEARCH SQUARE 2024:rs.3.rs-5361957. [PMID: 39678332 PMCID: PMC11643292 DOI: 10.21203/rs.3.rs-5361957/v1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/17/2024]
Abstract
There are limited longitudinal data from non-industrialized settings on patterns and determinants of gut bacterial microbiota development in early childhood. We analysed epidemiological data and stool samples collected from 60 children followed from early infancy to 5 years of age in a rural tropical district in coastal Ecuador. Data were collected longitudinally on a wide variety of individual, maternal, and household exposures. Extracted DNA from stool samples were analyzed for bacterial microbiota using 16S rRNA gene sequencing. Both alpha and beta diversity indices suggested stable profiles towards 5 years of age. Greater alpha diversity and lower beta diversity were associated with factors typical of rural poverty including low household incomes, overcrowding, and greater agricultural and animal exposures, but not with birth mode or antibiotic exposures. Consumption of unpasteurized milk was consistently associated with greater alpha diversity indices. Infants living in a non-industrialized setting in conditions of greater poverty and typically rural exposures appeared to acquire more rapidly a stable and diverse gut bacterial microbiome during childhood.
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Affiliation(s)
| | | | | | - Maritza Vaca
- Fundación Ecuatoriana Para la Investigación en Salud
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Toussaint Nguélé A, Mozzicafreddo M, Carrara C, Piersanti A, Salum SS, Ali SM, Miceli C. Interplay Between Helminth Infections, Malnutrition, and Gut Microbiota in Children and Mothers from Pemba, Tanzania: Potential of Microbiota-Directed Interventions. Nutrients 2024; 16:4023. [PMID: 39683417 DOI: 10.3390/nu16234023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2024] [Revised: 11/20/2024] [Accepted: 11/21/2024] [Indexed: 12/18/2024] Open
Abstract
BACKGROUND/OBJECTIVES Despite efforts within the framework of the Sustainable Development Goal to end malnutrition by 2030, malnutrition and soil-transmitted helminth infections persist in sub-Saharan Africa. A significant barrier to success is the inadequate understanding of effective intervention methods. Most research on the gut microbiota's role in health has been conducted in developed countries, leaving a critical gap in knowledge regarding low-income populations. This study addresses this gap by expanding research on the gut microbiota of underprivileged populations to help tackle these public health challenges. METHODS We employed 16S rDNA sequencing to assess the bacterial gut microbiota composition of 60 children (mean age: 26.63 ± 6.36 months) and their 58 mothers (mean age: 30.03 ± 6.31 years) in Pemba, with a focus on helminth infection and nutritional status. RESULTS Our differential abundance analysis identified bacterial taxa that were significantly negatively associated with both helminth infections and malnutrition, highlighting the potential for microbiota-directed interventions to address these health issues simultaneously. Notably, we identified Akkermansia, Blautia, Dorea, and Odoribacter as promising probiotic candidates for such interventions. In stunted children, positive co-occurrences were observed between Lactobacillus, Prevotella, and Bacteroides, while Escherichia/Shigella displayed negative co-abundance relationships with short-chain fatty acid (SCFA) producers in the gut microbiota. These findings suggest that administering Lactobacillus and SCFA-producing probiotics to children may foster the growth of beneficial bacteria like Prevotella and Bacteroides while reducing the relative abundance of Escherichia/Shigella, potentially enhancing overall health. CONCLUSIONS This study underscores the importance of microbiota-directed interventions in children and women of reproductive age as promising strategies, alongside established approaches, for combating helminth infections and malnutrition in vulnerable populations.
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Affiliation(s)
- Aristide Toussaint Nguélé
- School of Biosciences and Veterinary Medicine, University of Camerino, 62032 Camerino, Italy
- Institut Supérieur des Sciences de la Santé, Université Adventiste Cosendai, Nanga Eboko 04, Cameroon
| | - Matteo Mozzicafreddo
- Department of Clinical and Molecular Sciences, Marche Polytechnic University, 60126 Ancona, Italy
| | - Chiara Carrara
- School of Biosciences and Veterinary Medicine, University of Camerino, 62032 Camerino, Italy
| | - Angela Piersanti
- School of Biosciences and Veterinary Medicine, University of Camerino, 62032 Camerino, Italy
- Department of Biology, University of Padova, 35121 Padova, Italy
| | - Salum Seif Salum
- School of Health and Medical Sciences, State University of Zanzibar, Zanzibar City 146, Tanzania
| | - Said M Ali
- Public Health Laboratory Ivo de Carneri, Chake Chake 122, Tanzania
| | - Cristina Miceli
- School of Biosciences and Veterinary Medicine, University of Camerino, 62032 Camerino, Italy
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Pruss KM, Kao C, Byrne AE, Chen RY, Di Luccia B, Karvelyte L, Coskun R, Lemieux M, Nepal K, Webber DM, Hibberd MC, Wang Y, Rodionov DA, Osterman AL, Colonna M, Maueroder C, Ravichandran K, Barratt MJ, Ahmed T, Gordon JI. Effects of intergenerational transmission of small intestinal bacteria cultured from stunted Bangladeshi children with enteropathy. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.11.01.621574. [PMID: 39554152 PMCID: PMC11566026 DOI: 10.1101/2024.11.01.621574] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/19/2024]
Abstract
Environmental enteric dysfunction (EED), a small intestinal disorder found at a high prevalence in stunted children, is associated with gut mucosal barrier disruption and decreased absorptive capacity due to reduced intact small intestinal villi1-4. To test the hypothesis that intergenerational transmission of a perturbed small intestinal microbiota contributes to undernutrition by inducing EED5, we characterized two consortia of bacterial strains cultured from duodenal aspirates from stunted Bangladeshi children with EED - one of which induced local and systemic inflammation in gnotobiotic female mice. Offspring of dams that received this inflammatory consortium exhibited immunologic changes along their gut that phenocopied features of EED in children. Single nucleus plus bulk RNA-sequencing revealed alterations in inter-cellular signaling pathways related to intestinal epithelial cell renewal, barrier integrity and immune function while analyses of cerebral cortex disclosed alterations in glial- and endothelial-neuronal signaling pathways that regulate neural growth/axonal guidance, angiogenesis and inflammation. Analysis of ultrasonic vocalization calls in gnotobiotic P5-P9 pups indicated increased arousal and perturbed neurodevelopment in the offspring of dams harboring the inflammation-inducing consortium. Cohousing experiments and follow-up screening of candidate disease-promoting bacterial isolates identified a strain typically found in the oral microbiota (Campylobacter concisus) as a contributor to enteropathy. Given that fetal growth was also impaired in the dams with the consortium that induced enteropathy, this preclinical model allows the effects of the human small intestinal microbiota on both pre- and postnatal development to be ascertained, setting the stage for identification of small intestinal microbiota-targeted therapeutics for (intergenerational) undernutrition.
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Affiliation(s)
- Kali M. Pruss
- The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine; St. Louis, MO 63110, USA
- Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine; St. Louis, MO 63110, USA
| | - Clara Kao
- The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine; St. Louis, MO 63110, USA
- Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine; St. Louis, MO 63110, USA
| | - Alexandra E. Byrne
- The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine; St. Louis, MO 63110, USA
- Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine; St. Louis, MO 63110, USA
| | - Robert Y. Chen
- The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine; St. Louis, MO 63110, USA
- Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine; St. Louis, MO 63110, USA
| | - Blanda Di Luccia
- The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine; St. Louis, MO 63110, USA
- Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine; St. Louis, MO 63110, USA
- Division of Immunobiology, Department of Pathology and Immunology, Washington University School of Medicine; St. Louis, MO 63110, USA
| | - Laura Karvelyte
- Division of Immunobiology, Department of Pathology and Immunology, Washington University School of Medicine; St. Louis, MO 63110, USA
| | - Reyan Coskun
- The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine; St. Louis, MO 63110, USA
- Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine; St. Louis, MO 63110, USA
| | - Mackenzie Lemieux
- The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine; St. Louis, MO 63110, USA
- Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine; St. Louis, MO 63110, USA
| | - Keshav Nepal
- The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine; St. Louis, MO 63110, USA
- Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine; St. Louis, MO 63110, USA
| | - Daniel M. Webber
- The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine; St. Louis, MO 63110, USA
- Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine; St. Louis, MO 63110, USA
| | - Matthew C. Hibberd
- The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine; St. Louis, MO 63110, USA
- Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine; St. Louis, MO 63110, USA
| | - Yi Wang
- The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine; St. Louis, MO 63110, USA
- Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine; St. Louis, MO 63110, USA
| | - Dmitry A. Rodionov
- Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037 USA
| | - Andrei L. Osterman
- Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037 USA
| | - Marco Colonna
- Division of Immunobiology, Department of Pathology and Immunology, Washington University School of Medicine; St. Louis, MO 63110, USA
| | - Christian Maueroder
- Inflammation Research Centre, VIB, and the Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium
| | - Kodi Ravichandran
- Division of Immunobiology, Department of Pathology and Immunology, Washington University School of Medicine; St. Louis, MO 63110, USA
| | - Michael J. Barratt
- The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine; St. Louis, MO 63110, USA
- Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine; St. Louis, MO 63110, USA
| | - Tahmeed Ahmed
- International Center for Diarrhoeal Disease Research, Bangladesh (icddr,b); Dhaka 1212, Bangladesh
| | - Jeffrey I. Gordon
- The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine; St. Louis, MO 63110, USA
- Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine; St. Louis, MO 63110, USA
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Burcham ZM, Tweedie JL, Farfán-García AE, Nolan VG, Donohoe D, Gómez-Duarte OG, Johnson JG. Campylobacter infection of young children in Colombia and its impact on the gastrointestinal environment. mSphere 2024; 9:e0034224. [PMID: 39320095 PMCID: PMC11520299 DOI: 10.1128/msphere.00342-24] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2024] [Accepted: 08/26/2024] [Indexed: 09/26/2024] Open
Abstract
Campylobacter infections are a leading cause of bacterial-derived gastroenteritis worldwide with particularly profound impacts on pediatric patients in low- and middle-income countries. It remains unclear how Campylobacter impacts these hosts, though it is becoming increasingly evident that it is a multifactorial process that depends on the host immune response, the gastrointestinal microbiota, various bacterial factors, and host nutritional status. Since these factors likely vary between adult and pediatric patients in different regions of the world, it is important that studies define these attributes in well-characterized clinical cohorts in diverse settings. In this study, we analyzed the fecal microbiota and the metabolomic and micronutrient profiles of asymptomatic and symptomatic pediatric patients in Colombia who were either infected or uninfected with Campylobacter during a case-controlled study on acute diarrheal disease. Here, we report that the microbiome of Campylobacter-infected children only changed in their abundance of Campylobacter spp. despite the inclusion of children with or without diarrhea. In addition to increased Campylobacter, computational models were used to identify fecal metabolites that were associated with Campylobacter infection and found that glucose-6-phosphate and homovanillic acid were the strongest predictors of infection in these pediatric patients, which suggests that colonocyte metabolism is impacted during infection. Despite changes to the fecal metabolome, the concentrations of intestinal minerals and trace elements were not significantly impacted by Campylobacter infection but were elevated in uninfected children with diarrhea.IMPORTANCEGastrointestinal infection with pathogenic Campylobacter species has long been recognized as a significant cause of human morbidity. Recently, it has been observed that pediatric populations in low- and middle-income countries are uniquely impacted by these organisms in that infected children can be persistently colonized, develop enteric dysfunction, and exhibit reduced development and growth. While the association of Campylobacter species with these long-term effects continues to emerge, the impact of infection on the gastrointestinal environment of these children remains uncharacterized. To address this knowledge gap, our group leveraged clinical samples collected during a previous study on gastrointestinal infections in pediatric patients to examine the fecal microbiota, metabolome, and micronutrient profiles of those infected with Campylobacter species and found that the metabolome was impacted in a way that suggests gastrointestinal cell metabolism is affected during infection, which is some of the first data indicating how gastrointestinal health in these patients may be affected.
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Affiliation(s)
- Zachary M. Burcham
- Department of Microbiology, University of Tennessee, Knoxville, Tennessee, USA
| | - Jessie L. Tweedie
- Department of Microbiology, University of Tennessee, Knoxville, Tennessee, USA
| | - A. E. Farfán-García
- Grupo de Investigación en Manejo Clínico–CliniUDES, Facultad de Ciencias de la Salud, Universidad de Santander, Bucaramanga, Colombia
| | - Vikki G. Nolan
- School of Public Health, The University of Memphis, Memphis, Tennessee, USA
| | - Dallas Donohoe
- Department of Nutrition, University of Tennessee, Knoxville, Tennessee, USA
| | - Oscar G. Gómez-Duarte
- Division of Pediatric Infectious Diseases, Department of Pediatrics, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, USA
| | - Jeremiah G. Johnson
- Department of Microbiology, University of Tennessee, Knoxville, Tennessee, USA
- Department of Microbiology and Immunology, University of Iowa Carver College of Medicine, Iowa, lowa, USA
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Dai DLY, Petersen C, Turvey SE. Reduce, reinforce, and replenish: safeguarding the early-life microbiota to reduce intergenerational health disparities. Front Public Health 2024; 12:1455503. [PMID: 39507672 PMCID: PMC11537995 DOI: 10.3389/fpubh.2024.1455503] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2024] [Accepted: 10/02/2024] [Indexed: 11/08/2024] Open
Abstract
Socioeconomic (SE) disparity and health inequity are closely intertwined and associated with cross-generational increases in the rates of multiple chronic non-communicable diseases (NCDs) in North America and beyond. Coinciding with this social trend is an observed loss of biodiversity within the community of colonizing microbes that live in and on our bodies. Researchers have rightfully pointed to the microbiota as a key modifiable factor with the potential to ease existing health inequities. Although a number of studies have connected the adult microbiome to socioeconomic determinants and health outcomes, few studies have investigated the role of the infant microbiome in perpetuating these outcomes across generations. It is an essential and important question as the infant microbiota is highly sensitive to external forces, and observed shifts during this critical window often portend long-term outcomes of health and disease. While this is often studied in the context of direct modulators, such as delivery mode, family size, antibiotic exposure, and breastfeeding, many of these factors are tied to underlying socioeconomic and/or cross-generational factors. Exploring cross-generational socioeconomic and health inequities through the lens of the infant microbiome may provide valuable avenues to break these intergenerational cycles. In this review, we will focus on the impact of social inequality in infant microbiome development and discuss the benefits of prioritizing and restoring early-life microbiota maturation for reducing intergenerational health disparities.
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Affiliation(s)
| | | | - Stuart E. Turvey
- Department of Pediatrics, BC Children’s Hospital, University of British Columbia, Vancouver, BC, Canada
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Ratnayani, Hegar B, Sunardi D, Fadilah F, Gunardi H, Fahmida U, Vidiawati D. Association of Gut Microbiota Composition with Stunting Incidence in Children under Five in Jakarta Slums. Nutrients 2024; 16:3444. [PMID: 39458441 PMCID: PMC11510009 DOI: 10.3390/nu16203444] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2024] [Revised: 10/02/2024] [Accepted: 10/03/2024] [Indexed: 10/28/2024] Open
Abstract
BACKGROUND Stunting can be linked to various factors, one of which is dysbiosis. This study aims to analyze the microbiota composition and related contributing factors of stunted and non-stunted children in the slum areas of Jakarta. METHODS The subjects in this study included 21 stunted (HAZ ≤ -2SD) and 21 non-stunted children (-2SD ≤ HAZ ≤ 3SD) aged 2-5 years. Microbiota analysis was performed by extracting DNA from the subjects' feces and then via 16S rRNA sequencing using next-generation sequencing (NGS). RESULTS The results of this study showed that in stunted children, the abundance of Mitsuokella (24,469 OTUs), Alloprevotella (23,952 OTUs), and Providencia alcalifaciens (861 OTUs) was higher, while in non-stunted children, that of Blautia (29,755 OTUs), Lachnospiraceae (6134 OTUs), Bilophila (12,417 OTUs), Monoglobus (484 OTUs), Akkermansia muciniphila (1116 OTUs), Odoribacter splanchnicus (42,993 OTUs), and Bacteroides clarus (8900 OTUs) was higher. Differences in microbiota composition in the two groups were influenced by nutrient intake, birth history, breastfeeding history, handwashing habits before eating, drinking water sources, and water sources for other activities. CONCLUSIONS This study highlights that stunted children have a significantly different gut microbiota composition compared to non-stunted children, with higher levels of pathogenic bacteria and lower levels of beneficial bacteria. Future research should focus on interventions that can improve the gut microbiota composition to prevent stunting in children.
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Affiliation(s)
- Ratnayani
- Department of Nutrition, Faculty of Medicine, Universitas Indonesia—Dr. Cipto Mangunkusumo General Hospital, Jakarta 10430, Indonesia; (R.); (D.S.); (U.F.)
- Nutrition Study Program, Faculty of Health Sciences and Technology, Binawan University, Jakarta 13630, Indonesia
| | - Badriul Hegar
- Department of Child Health, Faculty of Medicine, Universitas Indonesia—Dr. Cipto Mangunkusumo Hospital, Jakarta 10430, Indonesia;
| | - Diana Sunardi
- Department of Nutrition, Faculty of Medicine, Universitas Indonesia—Dr. Cipto Mangunkusumo General Hospital, Jakarta 10430, Indonesia; (R.); (D.S.); (U.F.)
| | - Fadilah Fadilah
- Department of Chemistry, Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia;
- Bioinformatics Core Facilities, Institute of Medical Education and Research Indonesia (IMERI), Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia
| | - Hartono Gunardi
- Department of Child Health, Faculty of Medicine, Universitas Indonesia—Dr. Cipto Mangunkusumo Hospital, Jakarta 10430, Indonesia;
| | - Umi Fahmida
- Department of Nutrition, Faculty of Medicine, Universitas Indonesia—Dr. Cipto Mangunkusumo General Hospital, Jakarta 10430, Indonesia; (R.); (D.S.); (U.F.)
- Southeast Asian Ministers of Education Organization Regional Centre for Food and Nutrition (SEAMEO RECFON), Jakarta 13120, Indonesia
| | - Dhanasari Vidiawati
- Department of Community Medicine, Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia;
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9
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Houngbédji M, Jespersen JS, Wilfrid Padonou S, Jespersen L. Cereal-based fermented foods as microbiota-directed products for improved child nutrition and health in sub-Saharan Africa. Crit Rev Food Sci Nutr 2024:1-22. [PMID: 38973125 DOI: 10.1080/10408398.2024.2365342] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/09/2024]
Abstract
Several strategies, programs and policies have long been developed and implemented to alleviate child malnutrition in sub-Saharan African countries. However, stunting and wasting still persist at an alarming rate, suggesting that alternative strategies are needed to induce faster progress toward the 2030 SDGs targets of reducing malnutrition. Gut microbiota-directed intervention is now being recognized as an unconventional powerful approach to mitigate malnutrition and improve overall child health. In an African setting, manufactured probiotic and synbiotic foods or supplements may not be successful owing to the non-affordability and high attachment of African populations to their food tradition. This review analyses the potential of indigenous fermented cereal-based products including porridges, doughs, beverages, bread- and yoghurt-like products, to be used as microbiota-directed foods for over 6 months children. The discussion includes relevant strategies to effectively enhance the beneficial effects of these products on gut microbiota composition for improved child health and nutrition in sub-Saharan Africa. Characterization of probiotic features and general safety of food processing in sub-Saharan Africa as well as randomized clinical studies are still lacking to fully ascertain the health effects and suitability of these fermented foods in preventing and treating child malnutrition and diarrhea.
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Affiliation(s)
- Marcel Houngbédji
- Laboratoire de Sciences et Technologies des Aliments, Faculté des Sciences Agronomiques, Université d'Abomey-Calavi, Jéricho, Cotonou, Benin
- Laboratoire de Sciences et Technologie des Aliments, des Bioressources et de Nutrition Humaine, Université Nationale d'Agriculture, Sakété, Bénin
| | | | - Sègla Wilfrid Padonou
- Laboratoire de Sciences et Technologies des Aliments, Faculté des Sciences Agronomiques, Université d'Abomey-Calavi, Jéricho, Cotonou, Benin
- Laboratoire de Sciences et Technologie des Aliments, des Bioressources et de Nutrition Humaine, Université Nationale d'Agriculture, Sakété, Bénin
| | - Lene Jespersen
- Department of Food Science, University of Copenhagen, Copenhagen, Frederiksberg C, Denmark
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Chandel N, Maile A, Shrivastava S, Verma AK, Thakur V. Establishment and perturbation of human gut microbiome: common trends and variations between Indian and global populations. GUT MICROBIOME (CAMBRIDGE, ENGLAND) 2024; 5:e8. [PMID: 39776539 PMCID: PMC11704572 DOI: 10.1017/gmb.2024.6] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Revised: 05/23/2024] [Accepted: 05/24/2024] [Indexed: 01/11/2025]
Abstract
Human gut microbial species are crucial for dietary metabolism and biosynthesis of micronutrients. Digested products are utilised by the host as well as several gut bacterial species. These species are influenced by various factors such as diet, age, geographical location, and ethnicity. India is home to the largest human population in the world. It is spread across diverse ecological and geographical locations. With variable dietary habits and lifestyles, Indians have unique gut microbial composition. This review captures contrasting and common trends of gut bacterial community establishment in infants (born through different modes of delivery), and how that bacterial community manifests itself along infancy, through old age between Indian and global populations. Because dysbiosis of the gut community structure is associated with various diseases, this review also highlights the common and unique bacterial species associated with various communicable as well as noncommunicable diseases such as diarrhoea, amoebiasis, malnutrition, type 2 diabetes, obesity, colorectal cancer, inflammatory bowel disease, and gut inflammation and damage to the brain in the global and Indian population.
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Affiliation(s)
- Nisha Chandel
- Department of Systems and Computational Biology, University of Hyderabad, Hyderabad, India
| | - Anwesh Maile
- DBT-Centre for Microbial Informatics, University of Hyderabad, Hyderabad, India
| | - Suyesh Shrivastava
- ICMR-National Institute of Research in Tribal Health (NIRTH), Jabalpur, India
| | - Anil Kumar Verma
- ICMR-National Institute of Research in Tribal Health (NIRTH), Jabalpur, India
| | - Vivek Thakur
- Department of Systems and Computational Biology, University of Hyderabad, Hyderabad, India
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11
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Chibuye M, Mende DR, Spijker R, Simuyandi M, Luchen CC, Bosomprah S, Chilengi R, Schultsz C, Harris VC. Systematic review of associations between gut microbiome composition and stunting in under-five children. NPJ Biofilms Microbiomes 2024; 10:46. [PMID: 38782939 PMCID: PMC11116508 DOI: 10.1038/s41522-024-00517-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2023] [Accepted: 04/29/2024] [Indexed: 05/25/2024] Open
Abstract
Childhood stunting is associated with impaired cognitive development and increased risk of infections, morbidity, and mortality. The composition of the enteric microbiota may contribute to the pathogenesis of stunting. We systematically reviewed and synthesized data from studies using high-throughput genomic sequencing methods to characterize the gut microbiome in stunted versus non-stunted children under 5 years in LMICs. We included 14 studies from Asia, Africa, and South America. Most studies did not report any significant differences in the alpha diversity, while a significantly higher beta diversity was observed in stunted children in four out of seven studies that reported beta diversity. At the phylum level, inconsistent associations with stunting were observed for Bacillota, Pseudomonadota, and Bacteroidota phyla. No single genus was associated with stunted children across all 14 studies, and some associations were incongruent by specific genera. Nonetheless, stunting was associated with an abundance of pathobionts that could drive inflammation, such as Escherichia/Shigella and Campylobacter, and a reduction of butyrate producers, including Faecalibacterium, Megasphera, Blautia, and increased Ruminoccoccus. An abundance of taxa thought to originate in the oropharynx was also reported in duodenal and fecal samples of stunted children, while metabolic pathways, including purine and pyrimidine biosynthesis, vitamin B biosynthesis, and carbohydrate and amino acid degradation pathways, predicted linear growth. Current studies show that stunted children can have distinct microbial patterns compared to non-stunted children, which could contribute to the pathogenesis of stunting.
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Affiliation(s)
- Mwelwa Chibuye
- Department of Global Health, Amsterdam Institute for Global Health and Development (AIGHD), Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
- Research Division, Centre for Infectious Disease Research in Zambia, Lusaka, Zambia
- Amsterdam Institute of Infection and Immunity, Amsterdam University Medical Centers, Amsterdam, The Netherlands
| | - Daniel R Mende
- Amsterdam Institute of Infection and Immunity, Amsterdam University Medical Centers, Amsterdam, The Netherlands
- Department of Medical Microbiology and Infection Control, Amsterdam University Medical Centers, Amsterdam, The Netherlands
| | - Rene Spijker
- Department of Global Health, Amsterdam Institute for Global Health and Development (AIGHD), Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
| | - Michelo Simuyandi
- Research Division, Centre for Infectious Disease Research in Zambia, Lusaka, Zambia
| | - Chaluma C Luchen
- Department of Global Health, Amsterdam Institute for Global Health and Development (AIGHD), Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
- Research Division, Centre for Infectious Disease Research in Zambia, Lusaka, Zambia
| | - Samuel Bosomprah
- Research Division, Centre for Infectious Disease Research in Zambia, Lusaka, Zambia
- Department of Biostatistics, School of Public Health, University of Ghana, Legon, Accra, Ghana
| | - Roma Chilengi
- Research Division, Centre for Infectious Disease Research in Zambia, Lusaka, Zambia
- The Zambia National Public Health Institute (ZNPHI), Lusaka, Zambia
| | - Constance Schultsz
- Department of Global Health, Amsterdam Institute for Global Health and Development (AIGHD), Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
- Amsterdam Institute of Infection and Immunity, Amsterdam University Medical Centers, Amsterdam, The Netherlands
- Department of Medical Microbiology and Infection Control, Amsterdam University Medical Centers, Amsterdam, The Netherlands
| | - Vanessa C Harris
- Department of Global Health, Amsterdam Institute for Global Health and Development (AIGHD), Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands.
- Amsterdam Institute of Infection and Immunity, Amsterdam University Medical Centers, Amsterdam, The Netherlands.
- Division of Infectious Diseases, Department of Internal Medicine, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands.
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12
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Burcham ZM, Tweedie JL, Farfán-García AE, Nolan VG, Donohoe D, Gómez-Duarte OG, Johnson JG. Campylobacter infection of young children in Colombia and its impact on the gastrointestinal environment. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.05.06.592725. [PMID: 38766229 PMCID: PMC11100603 DOI: 10.1101/2024.05.06.592725] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/22/2024]
Abstract
Campylobacter infections are a leading cause of bacterial-derived gastroenteritis worldwide with particularly profound impacts on pediatric patients in low-and-middle income countries. It remains unclear how Campylobacter impacts these hosts, though it is becoming increasingly evident that it is a multifactorial process that depends on the host immune response, the gastrointestinal microbiota, various bacterial factors, and host nutritional status. Since these factors likely vary between adult and pediatric patients in different regions of the world, it is important that studies define these attributes in well characterized clinical cohorts in diverse settings. In this study, we analyzed the fecal microbiota and the metabolomic and micronutrient profiles of asymptomatic and symptomatic pediatric patients in Colombia that were either infected or uninfected with Campylobacter during a case-controlled study on acute diarrheal disease. Here, we report that the microbiome of Campylobacter- infected children only changed in their abundance of Campylobacter spp. despite the inclusion of children with or without diarrhea. In addition to increased Campylobacter, computational models were used to identify fecal metabolites that were associated with Campylobacter infection and found that glucose-6-phosphate and homovanillic acid were the strongest predictors of infection in these pediatric patients, which suggest that colonocyte metabolism are impacted during infection. Despite changes to the fecal metabolome, the concentrations of intestinal minerals and trace elements were not significantly impacted by Campylobacter infection, but were elevated in uninfected children with diarrhea. Importance Gastrointestinal infection with pathogenic Campylobacter species has long been recognized as a significant cause of human morbidity. Recently, it has been observed that pediatric populations in low-and-middle income countries are uniquely impacted by these organisms in that infected children can be persistently colonized, develop enteric dysfunction, and exhibit reduced development and growth. While the association of Campylobacter species with these long-term effects continues to emerge, the impact of infection on the gastrointestinal environment of these children remains uncharacterized. To address this knowledge gap, our group leveraged clinical samples collected during a previous study on gastrointestinal infections in pediatric patients to examine the fecal microbiota, metabolome, and micronutrient profiles of those infected with Campylobacter species, and found that the metabolome was impacted in a way that suggests gastrointestinal cell metabolism is affected during infection, which is some of the first data indicating how gastrointestinal health in these patients may be affected.
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13
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Hardjo J, Selene NB. Stunting and Gut Microbiota: A Literature Review. Pediatr Gastroenterol Hepatol Nutr 2024; 27:137-145. [PMID: 38818278 PMCID: PMC11134181 DOI: 10.5223/pghn.2024.27.3.137] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Revised: 12/07/2023] [Accepted: 01/02/2024] [Indexed: 06/01/2024] Open
Abstract
Stunting, a condition characterized by impaired growth and development in children, remains a major public health concern worldwide. Over the past decade, emerging evidence has shed light on the potential role of gut microbiota modulation in stunting. Gut microbiota dysbiosis has been linked to impaired nutrient absorption, chronic inflammation, altered short-chain fatty acid production, and perturbed hormonal and signaling pathways, all of which may hinder optimal growth in children. This review aims to provide a comprehensive analysis of existing research exploring the bidirectional relationship between stunting and the gut microbiota. Although stunting can alter the gut microbial community, microbiota dysbiosis may exacerbate it, forming a vicious cycle that sustains the condition. The need for effective preventive and therapeutic strategies targeting the gut microbiota to combat stunting is also discussed. Nutritional interventions, probiotics, and prebiotics are among the most promising approaches to modulate the gut microbiota and potentially ameliorate stunting outcomes. Ultimately, a better understanding of the gut microbiota-stunting nexus is vital for guiding evidence-based interventions that can improve the growth and development trajectory of children worldwide, making substantial strides toward reducing the burden of stunting in vulnerable populations.
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Affiliation(s)
- Jessy Hardjo
- Department of Emergency Medicine, General Hospital Ploso, East Java, Indonesia
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14
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Zoghi S, Sadeghpour Heravi F, Nikniaz Z, Shirmohamadi M, Moaddab SY, Ebrahimzadeh Leylabadlo H. Gut microbiota and childhood malnutrition: Understanding the link and exploring therapeutic interventions. Eng Life Sci 2024; 24:2300070. [PMID: 38708416 PMCID: PMC11065333 DOI: 10.1002/elsc.202300070] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Revised: 09/12/2023] [Accepted: 09/22/2023] [Indexed: 05/07/2024] Open
Abstract
Childhood malnutrition is a metabolic condition that affects the physical and mental well-being of children and leads to resultant disorders in maturity. The development of childhood malnutrition is influenced by a number of physiological and environmental factors including metabolic stress, infections, diet, genetic variables, and gut microbiota. The imbalanced gut microbiota is one of the main environmental risk factors that significantly influence host physiology and childhood malnutrition progression. In this review, we have evaluated the gut microbiota association with undernutrition and overnutrition in children, and then the quantitative and qualitative significance of gut dysbiosis in order to reveal the impact of gut microbiota modification using probiotics, prebiotics, synbiotics, postbiotics, fecal microbiota transplantation, and engineering biology methods as new therapeutic challenges in the management of disturbed energy homeostasis. Understanding the host-microbiota interaction and the remote regulation of other organs and pathways by gut microbiota can improve the effectiveness of new therapeutic approaches and mitigate the negative consequences of childhood malnutrition.
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Affiliation(s)
- Sevda Zoghi
- Liver and Gastrointestinal Diseases Research CenterTabriz University of Medical SciencesTabrizIran
| | | | - Zeinab Nikniaz
- Liver and Gastrointestinal Diseases Research CenterTabriz University of Medical SciencesTabrizIran
| | - Masoud Shirmohamadi
- Liver and Gastrointestinal Diseases Research CenterTabriz University of Medical SciencesTabrizIran
| | - Seyed Yaghoub Moaddab
- Liver and Gastrointestinal Diseases Research CenterTabriz University of Medical SciencesTabrizIran
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15
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Shennon I, Wilson BC, Behling AH, Portlock T, Haque R, Forrester T, Nelson CA, O'Sullivan JM. The infant gut microbiome and cognitive development in malnutrition. Clin Nutr 2024; 43:1181-1189. [PMID: 38608404 DOI: 10.1016/j.clnu.2024.03.029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2023] [Revised: 03/11/2024] [Accepted: 03/29/2024] [Indexed: 04/14/2024]
Abstract
Malnutrition affects 195 million children under the age of five worldwide with long term effects that include impaired cognitive development. Brain development occurs rapidly over the first 36 months of life. Whilst seemingly independent, changes to the brain and gut microbiome are linked by metabolites, hormones, and neurotransmitters as part of the gut-brain axis. In the context of severe malnutrition, the composition of the gut microbiome and the repertoire of biochemicals exchanged via the gut-brain axis vary when compared to healthy individuals. These effects are primarily due to the recognized interacting determinants, macro- and micronutrient deficiencies, infection, infestations and toxins related to poor sanitation, and a dearth of psycho-social stimulation. The standard of care for the treatment of severe acute malnutrition is focused on nutritional repletion and weight restoration through the provision of macro- and micronutrients, the latter usually in excess of recommended dietary allowances (RDA). However, existing formulations and supplements have not been designed to specifically address key recovery requirements for brain and gut microbiome development. Animal model studies indicate that treatments targeting the gut microbiome could improve brain development. Despite this, research on humans targeting the gut microbiome with the aim of restoring brain functionality are scarce. We conclude that there is a need for assessment of cognition and the use of various tools that permit visualization of the brain anatomy and function (e.g., Magnetic resonance imaging (MRI), functional near-infrared spectroscopy (fNIRS), electroencephalogram (EEG)) to understand how interventions targeting the gut microbiome impact brain development.
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Affiliation(s)
- Inoli Shennon
- The Liggins Institute, The University of Auckland, Auckland 1023, New Zealand
| | - Brooke C Wilson
- The Liggins Institute, The University of Auckland, Auckland 1023, New Zealand
| | - Anna H Behling
- The Liggins Institute, The University of Auckland, Auckland 1023, New Zealand
| | - Theo Portlock
- The Liggins Institute, The University of Auckland, Auckland 1023, New Zealand
| | - Rashidul Haque
- Infectious Disease Division, International Centre for Diarrheal Disease Research, Bangladesh
| | - Terrence Forrester
- UWI Solutions for Developing Countries, The University of the West Indies, Mona, Kingston 7, Jamaica
| | - Charles A Nelson
- Department of Pediatrics, Division of Developmental Medicine, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA; Harvard Graduate School of Education, Cambridge, MA, USA
| | - Justin M O'Sullivan
- The Liggins Institute, The University of Auckland, Auckland 1023, New Zealand; The Maurice Wilkins Centre, The University of Auckland, Auckland 1010, New Zealand; MRC Lifecourse Epidemiology Unit, University of Southampton, University Road, Southampton SO17 1BJ, UK; Singapore Institute for Clinical Sciences, Agency for Science Technology and Research, Singapore.
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16
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Surono IS, Popov I, Verbruggen S, Verhoeven J, Kusumo PD, Venema K. Gut microbiota differences in stunted and normal-lenght children aged 36-45 months in East Nusa Tenggara, Indonesia. PLoS One 2024; 19:e0299349. [PMID: 38551926 PMCID: PMC10980242 DOI: 10.1371/journal.pone.0299349] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2023] [Accepted: 02/06/2024] [Indexed: 04/01/2024] Open
Abstract
The role of the gut microbiota in energy metabolism of the host has been established, both in overweight/obesity, as well as in undernutrition/stunting. Dysbiosis of the gut microbiota may predispose to stunting. The aim of this study was to compare the gut microbiota composition of stunted Indonesian children and non-stunted children between 36 and 45 months from two sites on the East Nusa Tenggara (ENT) islands. Fecal samples were collected from 100 stunted children and 100 non-stunted children in Kupang and North Kodi. The gut microbiota composition was determined by sequencing amplicons of the V3-V4 region of the 16S rRNA gene. Moreover, fecal SCFA concentrations were analyzed. The microbiota composition was correlated to anthropometric parameters and fecal metabolites. The phyla Bacteroidetes (Bacteroidota; q = 0.014) and Cyanobacteria (q = 0.049) were significantly higher in stunted children. Three taxa at genus levels were consistently significantly higher in stunted children at both sampling sites, namely Lachnoclostridium, Faecalibacterium and Veillonella (q < 7 * 10-4). These and 9 other taxa positively correlated to the z-score length-for-age (zlen), while 11 taxa negatively correlated with zlen. Several taxa also correlated with sanitary parameters, some of which were also significantly different between the two groups. All three fecal SCFA concentrations (acetate, propionate and butyrate) and their total were lower in stunted children compared to non-stunted children, although not significant for butyrate, indicating lower energy-extraction by the gut microbiota. Also, since SCFA have been shown to be involved in gut barrier function, barrier integrity may be affected in the stunted children. It remains to be seen if the three taxa are involved in stunting, or are changed due to e.g. differences in diet, hygiene status, or other factors. The observed differences in this study do not agree with our previous observations in children on Java, Indonesia. There are differences in infrastructure facilities such as clean water and sanitation on ENT and Java, which may contribute to the differences observed. The role of the gut microbiota in stunting therefore requires more in depth studies. Trial registration: the trial was registered at ClinicalTrials.gov with identifier number NCT05119218.
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Affiliation(s)
- Ingrid S. Surono
- Faculty of Engineering, Food Technology Department, Bina Nusantara University, Jakarta, Indonesia
| | - Ilia Popov
- Faculty of Engineering, Food Technology Department, Bina Nusantara University, Jakarta, Indonesia
| | - Sanne Verbruggen
- Centre for Healthy Eating & Food Innovation, Maastricht University—Campus Venlo, Venlo, The Netherlands
| | - Jessica Verhoeven
- Centre for Healthy Eating & Food Innovation, Maastricht University—Campus Venlo, Venlo, The Netherlands
| | - Pratiwi D. Kusumo
- Faculty of Medicine, Universitas Kristen Indonesia, Jakarta, Indonesia
| | - Koen Venema
- Centre for Healthy Eating & Food Innovation, Maastricht University—Campus Venlo, Venlo, The Netherlands
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17
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Hussein N, Rajasuriar R, Khan AM, Lim YAL, Gan GG. The Role of the Gut Microbiome in Hematological Cancers. Mol Cancer Res 2024; 22:7-20. [PMID: 37906201 DOI: 10.1158/1541-7786.mcr-23-0080] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2023] [Revised: 06/23/2023] [Accepted: 10/27/2023] [Indexed: 11/02/2023]
Abstract
Humans are in a complex symbiotic relationship with a wide range of microbial organisms, including bacteria, viruses, and fungi. The evolution and composition of the human microbiome can be an indicator of how it may affect human health and susceptibility to diseases. Microbiome alteration, termed as dysbiosis, has been linked to the pathogenesis and progression of hematological cancers. A variety of mechanisms, including epithelial barrier disruption, local chronic inflammation response trigger, antigen dis-sequestration, and molecular mimicry, have been proposed to be associated with gut microbiota. Dysbiosis may be induced or worsened by cancer therapies (such as chemotherapy and/or hematopoietic stem cell transplantation) or infection. The use of antibiotics during treatment may also promote dysbiosis, with possible long-term consequences. The aim of this review is to provide a succinct summary of the current knowledge describing the role of the microbiome in hematological cancers, as well as its influence on their therapies. Modulation of the gut microbiome, involving modifying the composition of the beneficial microorganisms in the management and treatment of hematological cancers is also discussed. Additionally discussed are the latest developments in modeling approaches and tools used for computational analyses, interpretation and better understanding of the gut microbiome data.
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Affiliation(s)
- Najihah Hussein
- Department of Medicine, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia
| | - Reena Rajasuriar
- Department of Medicine, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia
| | - Asif M Khan
- School of Data Sciences, Perdana University, Kuala Lumpur, Malaysia
- Beykoz Institute of Life Sciences and Biotechnology, Bezmialem Vakif University, Istanbul, Turkiye
- College of Computing and Information Technology, University of Doha for Science and Technology, Doha, Qatar
| | - Yvonne Ai-Lian Lim
- Department of Parasitology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia
| | - Gin Gin Gan
- Department of Medicine, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia
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18
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Rinanda T, Riani C, Artarini A, Sasongko L. Correlation between gut microbiota composition, enteric infections and linear growth impairment: a case-control study in childhood stunting in Pidie, Aceh, Indonesia. Gut Pathog 2023; 15:54. [PMID: 37946290 PMCID: PMC10636988 DOI: 10.1186/s13099-023-00581-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2023] [Accepted: 10/30/2023] [Indexed: 11/12/2023] Open
Abstract
BACKGROUND Gut microbiota is pivotal in maintaining children's health and well-being. The ingestion of enteric pathogens and dysbiosis lead to Environmental Enteric Dysfunction (EED), which is essential in stunting pathogenesis. The roles of gut microbiome and enteric infections have not been explored comprehensively in relation to childhood stunting in Indonesia. This study aimed to determine the correlation between gut microbiota composition, enteric infections, and growth biomarker, Insulin-like Growth Factor 1 (IGF-1), in stunted children from Pidie, Aceh, Indonesia. METHODS This study was a case-control study involving 42 subjects aged 24 to 59 months, comprising 21 stunted children for the case and 21 normal children for the control group. The IGF-1 serum level was quantified using ELISA. The gut microbiome profiling was conducted using 16S rDNA amplicon sequencing. The expression of enteric pathogens virulence genes was determined using quantitative PCR (qPCR) assay. The correlations of observed variables were analysed using suitable statistical analyses. RESULTS The result showed that the IGF-1 sera levels in stunted were lower than those in normal children (p ≤ 0.001). The abundance of Firmicutes (50%) was higher than Bacteroidetes (34%) in stunted children. The gut microbiome profile of stunted children showed enriched genera such as Blautia, Dorea, Collinsella, Streptococcus, Clostridium sensu stricto 13, Asteroleplasma and Anaerostipes. Meanwhile the depleted genera comprised Prevotella, Lactococcus, Butyrivibrio, Muribaculaceae, Alloprevotella, Akkermansia, Enterococcus, Terrisporobacter and Turicibacter. The abundance of water biological contaminants such as Aeromonas, Stappiaceae, and Synechococcus was also higher in stunted children compared to normal children. The virulence genes expression of Enteroaggregative Escherichia coli (aaiC), Enterotoxigenic E. coli (estA), Enteropathogenic E. coli (eaeA), Shigella/Enteroinvasive E. coli (ipaH3) and Salmonella enterica (ompC) in stunted was higher than in normal children (p ≤ 0.001), which negatively correlated to height and level of IGF-1. CONCLUSION The present study showed the distinctive gut microbiome profile of stunted and normal children from Pidie, Aceh, Indonesia. The gut microbiota of stunted children revealed dysbiosis, comprised several pro-inflammatory, metabolic abnormalities and high-fat/low-fiber diet-related taxa, and expressed virulence genes of enteric pathogens. These findings provide evidence that it is imperative to restore dysbiosis and preserve the balance of gut microbiota to support linear growth in children.
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Affiliation(s)
- Tristia Rinanda
- Department of Pharmaceutics, School of Pharmacy, Institut Teknologi Bandung, Ganesha 10, Bandung, 40132, West Java, Indonesia
- Department of Microbiology, Faculty of Medicine, Universitas Syiah Kuala, Darussalam, Banda Aceh, 23111, Aceh, Indonesia
| | - Catur Riani
- Department of Pharmaceutics, School of Pharmacy, Institut Teknologi Bandung, Ganesha 10, Bandung, 40132, West Java, Indonesia
| | - Anita Artarini
- Department of Pharmaceutics, School of Pharmacy, Institut Teknologi Bandung, Ganesha 10, Bandung, 40132, West Java, Indonesia
| | - Lucy Sasongko
- Department of Pharmaceutics, School of Pharmacy, Institut Teknologi Bandung, Ganesha 10, Bandung, 40132, West Java, Indonesia.
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19
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Jones HJ, Bourke CD, Swann JR, Robertson RC. Malnourished Microbes: Host-Microbiome Interactions in Child Undernutrition. Annu Rev Nutr 2023; 43:327-353. [PMID: 37207356 DOI: 10.1146/annurev-nutr-061121-091234] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/21/2023]
Abstract
Childhood undernutrition is a major global health burden that is only partially resolved by nutritional interventions. Both chronic and acute forms of child undernutrition are characterized by derangements in multiple biological systems including metabolism, immunity, and endocrine systems. A growing body of evidence supports a role of the gut microbiome in mediating these pathways influencing early life growth. Observational studies report alterations in the gut microbiome of undernourished children, while preclinical studies suggest that this can trigger intestinal enteropathy, alter host metabolism, and disrupt immune-mediated resistance against enteropathogens, each of which contribute to poor early life growth. Here, we compile evidence from preclinical and clinical studies and describe the emerging pathophysiological pathways by which the early life gut microbiome influences host metabolism, immunity, intestinal function, endocrine regulation, and other pathways contributing to child undernutrition. We discuss emerging microbiome-directed therapies and consider future research directions to identify and target microbiome-sensitive pathways in child undernutrition.
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Affiliation(s)
- Helen J Jones
- Centre for Genomics & Child Health, Blizard Institute, Queen Mary University of London, London, United Kingdom;
| | - Claire D Bourke
- Centre for Genomics & Child Health, Blizard Institute, Queen Mary University of London, London, United Kingdom;
| | - Jonathan R Swann
- Department of Metabolism, Digestion and Reproduction, Imperial College London, London, United Kingdom
- School of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, United Kingdom
| | - Ruairi C Robertson
- Centre for Genomics & Child Health, Blizard Institute, Queen Mary University of London, London, United Kingdom;
- Microenvironment and Immunity Unit, INSERM U1224, Institut Pasteur, Université Paris Cité, Paris, France
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20
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Mathews T, Hayer SS, Dinkel D, Hanish A, Poppert Cordts KM, Rasmussen H, Moore T. Maternal-Child Microbiome and Impact on Growth and Neurodevelopment in Infants and Children: A Scoping Review. Biol Res Nurs 2023; 25:454-468. [PMID: 36607703 DOI: 10.1177/10998004221151179] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
BACKGROUND Pathologic changes in the microbiome (dysbiosis) have been implicated in affecting the growth and neurodevelopment of infants and children. There is evidence to suggest that prenatal and postnatal stressors may be a factor in dysbiosis and there is also a growing body of evidence to suggest that interventions may reduce this negative impact. A scoping review was undertaken to identify association between maternal and/or child microbiome with child growth and neurodevelopment. Additionally, intervention studies such as use of nutritional supplementation and its impact on the microbiome, growth and neurodevelopment were reviewed. METHODS An exhaustive literature search identified 654 relevant citations. After review of abstracts, 557 were eliminated, and 97 remained for full text review. We identified and reported on 42 articles which met inclusion criteria. RESULTS Seven studies examined associations between microbiome and neurodevelopment and 36 studies evaluated anthropometric measurements, most commonly weight, and microbiota relationships. One study evaluated both growth and neurodevelopment and microbiota. Fourteen studies evaluated supplemental nutrients. Preterm, low birth weight (LBW), and very low birth weight (VLBW) infants were most studied. Findings were inconclusive for consistent associations between microbiota and growth and neurodevelopment. Further, there were no consistent conclusive changes with prescribed treatment interventions. DISCUSSION There is a need for high-quality longitudinal studies evaluating repeated developmental assessment measures using consistent microbial analysis techniques to inform conclusions regarding the association between microbiome and infant and child growth and neurodevelopment. Additional intervention studies that may mitigate dysbiosis are warranted.
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Affiliation(s)
- Therese Mathews
- College of Nursing, University of Nebraska Medical Center, Omaha, NE, USA
| | - Shivdeep S Hayer
- Department of Biology, College of Arts and Sciences, University of Nebraska at Omaha, Omaha, NE, USA
| | - Danae Dinkel
- School of Health and Kinesiology, University of Nebraska at Omaha, Omaha, NE, USA
| | - Alyson Hanish
- College of Nursing, University of Nebraska Medical Center, Omaha, NE, USA
| | - Katrina M Poppert Cordts
- College of Medicine, Department of Psychiatry, University of Nebraska Medical Center, Omaha, NE, USA
| | - Heather Rasmussen
- College of Education & Human Sciences, University of Nebraska-Lincoln, Lincoln, NE, USA
| | - Tiffany Moore
- College of Nursing, University of Nebraska Medical Center, Omaha, NE, USA
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21
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Jannat K, Agho KE, Parvez SM, Rahman M, Thomson R, Amin MB, Merom D. The Effects of Yogurt Supplementation and Nutritional Education on Malnourished Infants: A Pilot RCT in Dhaka's Slums. Nutrients 2023; 15:2986. [PMID: 37447313 PMCID: PMC10346178 DOI: 10.3390/nu15132986] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Revised: 06/26/2023] [Accepted: 06/27/2023] [Indexed: 07/15/2023] Open
Abstract
Our objective was to quantify the effects of yogurt supplementation and nutrition education over three months on the linear growth of infants at risk of stunting. We conducted a three-arm pilot randomized controlled trial: (1) nutrition education for mothers; (2) nutrition education plus a daily yogurt supplement (50 g) for the index child; and (3) usual care (control). Dyads of children aged 4-6 months and at risk of stunting [length-for-age z-score (LAZ) ≤ -1 SD and >-2 SD] and their mothers with ≤10 years of education were eligible for the study. Participants were recruited from five slum areas in Dhaka, Bangladesh. Intention-to-treat (N = 162) and complete-case analyses (N = 127) showed no between-group statistically significant differences in LAZ or weight-for-age (WAZ). However, the yogurt group showed greater change in linear growth compared to the control (LAZ: mean difference 0.20, 95% CI: -0.06, 0.47, p-value 0.13), which was also slightly greater than the education-only group. Children in the yogurt plus group were five times (95% CI: 0.80, 31.80, p-value 0.09) more likely to meet the minimum dietary diversity (MDD) score compared to the control. A 3-month follow-up of this pilot study did not demonstrate that yogurt was beneficial to linear growth. However, there were encouraging trends that merit replication of the intervention with larger samples and longer follow-ups.
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Affiliation(s)
- Kaniz Jannat
- Centre for Research in Mathematics and Data Science, School of Health Sciences, Western Sydney University, Locked Bag 1797, Penrith, NSW 2751, Australia; (K.E.A.); (R.T.); (D.M.)
| | - Kingsley Emwinyore Agho
- Centre for Research in Mathematics and Data Science, School of Health Sciences, Western Sydney University, Locked Bag 1797, Penrith, NSW 2751, Australia; (K.E.A.); (R.T.); (D.M.)
| | - Sarker Masud Parvez
- Environmental Interventions Unit, Laboratory of Food Safety and One Health, Infectious Disease Division, Laboratory Sciences and Services Division, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka 1212, Bangladesh; (S.M.P.); (M.R.); (M.B.A.)
- Children’s Health and Environment Program, Child Health Research Centre, The University of Queensland, South Brisbane, QLD 4101, Australia
| | - Mahbubur Rahman
- Environmental Interventions Unit, Laboratory of Food Safety and One Health, Infectious Disease Division, Laboratory Sciences and Services Division, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka 1212, Bangladesh; (S.M.P.); (M.R.); (M.B.A.)
| | - Russell Thomson
- Centre for Research in Mathematics and Data Science, School of Health Sciences, Western Sydney University, Locked Bag 1797, Penrith, NSW 2751, Australia; (K.E.A.); (R.T.); (D.M.)
| | - Mohammed Badrul Amin
- Environmental Interventions Unit, Laboratory of Food Safety and One Health, Infectious Disease Division, Laboratory Sciences and Services Division, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka 1212, Bangladesh; (S.M.P.); (M.R.); (M.B.A.)
| | - Dafna Merom
- Centre for Research in Mathematics and Data Science, School of Health Sciences, Western Sydney University, Locked Bag 1797, Penrith, NSW 2751, Australia; (K.E.A.); (R.T.); (D.M.)
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22
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Hidalgo-Villeda F, Million M, Defoort C, Vannier T, Svilar L, Lagier M, Wagner C, Arroyo-Portilla C, Chasson L, Luciani C, Bossi V, Gorvel JP, Lelouard H, Tomas J. Prolonged dysbiosis and altered immunity under nutritional intervention in a physiological mouse model of severe acute malnutrition. iScience 2023; 26:106910. [PMID: 37378323 PMCID: PMC10291336 DOI: 10.1016/j.isci.2023.106910] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2023] [Revised: 04/03/2023] [Accepted: 05/12/2023] [Indexed: 06/29/2023] Open
Abstract
Severe acute malnutrition (SAM) is a multifactorial disease affecting millions of children worldwide. It is associated with changes in intestinal physiology, microbiota, and mucosal immunity, emphasizing the need for multidisciplinary studies to unravel its full pathogenesis. We established an experimental model in which weanling mice fed a high-deficiency diet mimic key anthropometric and physiological features of SAM in children. This diet alters the intestinal microbiota (less segmented filamentous bacteria, spatial proximity to epithelium), metabolism (decreased butyrate), and immune cell populations (depletion of LysoDC in Peyer's patches and intestinal Th17 cells). A nutritional intervention leads to a fast zoometric and intestinal physiology recovery but to an incomplete restoration of the intestinal microbiota, metabolism, and immune system. Altogether, we provide a preclinical model of SAM and have identified key markers to target with future interventions during the education of the immune system to improve SAM whole defects.
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Affiliation(s)
- Fanny Hidalgo-Villeda
- Aix Marseille University, CNRS, INSERM, CIML, Turing Centre for Living Systems, Marseille, France
- Escuela de Microbiología, Facultad de Ciencias, Universidad Nacional Autónoma de Honduras, Tegucigalpa, Honduras
- IHU-Méditerranée Infection, Marseille, France
| | - Matthieu Million
- IHU-Méditerranée Infection, Marseille, France
- Ap-HM, Marseille, France
| | - Catherine Defoort
- C2VN, INRA, INSERM, Aix Marseille University, CriBioM, Marseille, France
| | - Thomas Vannier
- Aix Marseille University, CNRS, INSERM, CIML, Turing Centre for Living Systems, Marseille, France
| | - Ljubica Svilar
- C2VN, INRA, INSERM, Aix Marseille University, CriBioM, Marseille, France
| | - Margaux Lagier
- Aix Marseille University, CNRS, INSERM, CIML, Turing Centre for Living Systems, Marseille, France
| | - Camille Wagner
- Aix Marseille University, CNRS, INSERM, CIML, Turing Centre for Living Systems, Marseille, France
| | - Cynthia Arroyo-Portilla
- Aix Marseille University, CNRS, INSERM, CIML, Turing Centre for Living Systems, Marseille, France
- Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica
| | - Lionel Chasson
- Aix Marseille University, CNRS, INSERM, CIML, Turing Centre for Living Systems, Marseille, France
| | - Cécilia Luciani
- Aix Marseille University, CNRS, INSERM, CIML, Turing Centre for Living Systems, Marseille, France
| | | | - Jean-Pierre Gorvel
- Aix Marseille University, CNRS, INSERM, CIML, Turing Centre for Living Systems, Marseille, France
| | - Hugues Lelouard
- Aix Marseille University, CNRS, INSERM, CIML, Turing Centre for Living Systems, Marseille, France
| | - Julie Tomas
- Aix Marseille University, CNRS, INSERM, CIML, Turing Centre for Living Systems, Marseille, France
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23
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Veeraraghavan B, Kesavelu D, Yadav B. Gut Microbiota Composition in Indian and Western Infants (0–24 Months): A Systematic Review. NUTRITION AND DIETARY SUPPLEMENTS 2023. [DOI: 10.2147/nds.s402256] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/08/2023] Open
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24
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Balaji V, Dinh DM, Kane AV, Soofi S, Ahmed I, Rizvi A, Chatterjee M, Babji S, Duara J, Moy J, Naumova EN, Wanke CA, Ward HD, Bhutta ZA. Longitudinal Analysis of the Intestinal Microbiota among a Cohort of Children in Rural and Urban Areas of Pakistan. Nutrients 2023; 15:1213. [PMID: 36904212 PMCID: PMC10005232 DOI: 10.3390/nu15051213] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2022] [Revised: 02/09/2023] [Accepted: 02/20/2023] [Indexed: 03/04/2023] Open
Abstract
The profile of the intestinal microbiota is known to be altered in malnourished young children in low- and middle-income countries. However, there are limited studies longitudinally evaluating the intestinal microbiota in malnourished young children in resource-limited settings over the first two years of life. In this longitudinal pilot study, we determined the effect of age, residential location, and intervention on the composition, relative abundance, and diversity of the intestinal microbiota in a representative sample of children under 24 months of age with no diarrhea in the preceding 72 h in the urban and rural areas of Sindh, Pakistan nested within a cluster-randomized trial evaluating the effect of zinc and micronutrients on growth and morbidity (ClinicalTrials.gov Identifier: NCT00705445). The major findings were age-related with significant changes in alpha and beta diversity with increasing age. There was a significant increase in the relative abundance of the Firmicutes and Bacteroidetes phyla and a significant decrease in that of the Actinobacteria and Proteobacteria phyla (p < 0.0001). There were significant increases in the relative abundances of the major genera Bifidobacterium, Escherichia/Shigella and Streptococcus (p < 0.0001), and no significant change in the relative abundance of Lactobacillus. Using the LEfSE algorithm, differentially abundant taxa were identified between children in the first and second years of age, between those residing in rural and urban areas, and those who received different interventions at different ages from 3 to 24 months. The numbers of malnourished (underweight, wasted, stunted) or well-nourished children at each age, in each intervention arm, and at urban or rural sites were too small to determine if there were significant differences in alpha or beta diversity or differentially abundant taxa among them. Further longitudinal studies with larger numbers of well-nourished and malnourished children are required to fully characterize the intestinal microbiota of children in this region.
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Affiliation(s)
- Veeraraghavan Balaji
- Division of Geographic Medicine and Infectious Diseases, Tufts Medical Center, Boston, MA 02111, USA
- Department of Microbiology, Christian Medical College, Vellore 632004, India
| | - Duy M. Dinh
- Division of Geographic Medicine and Infectious Diseases, Tufts Medical Center, Boston, MA 02111, USA
| | - Anne V. Kane
- Division of Geographic Medicine and Infectious Diseases, Tufts Medical Center, Boston, MA 02111, USA
| | - Sajid Soofi
- Division of Nutrition Data Sciences, Center of Excellence in Women and Child Health, The Aga Khan University, Karachi 74800, Pakistan
| | - Imran Ahmed
- Division of Nutrition Data Sciences, Center of Excellence in Women and Child Health, The Aga Khan University, Karachi 74800, Pakistan
| | - Arjumand Rizvi
- Division of Nutrition Data Sciences, Center of Excellence in Women and Child Health, The Aga Khan University, Karachi 74800, Pakistan
| | - Meera Chatterjee
- Division of Geographic Medicine and Infectious Diseases, Tufts Medical Center, Boston, MA 02111, USA
| | - Sudhir Babji
- Division of Geographic Medicine and Infectious Diseases, Tufts Medical Center, Boston, MA 02111, USA
- Department of Microbiology, Christian Medical College, Vellore 632004, India
| | - Joanne Duara
- Division of Geographic Medicine and Infectious Diseases, Tufts Medical Center, Boston, MA 02111, USA
| | - Joy Moy
- Division of Geographic Medicine and Infectious Diseases, Tufts Medical Center, Boston, MA 02111, USA
| | - Elena N. Naumova
- Gerald J. and Dorothy R. Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA 02111, USA
- Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, MA 02111, USA
| | - Christine A. Wanke
- Division of Geographic Medicine and Infectious Diseases, Tufts Medical Center, Boston, MA 02111, USA
- Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, MA 02111, USA
| | - Honorine D. Ward
- Division of Geographic Medicine and Infectious Diseases, Tufts Medical Center, Boston, MA 02111, USA
- Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, MA 02111, USA
| | - Zulfiqar A. Bhutta
- Division of Nutrition Data Sciences, Center of Excellence in Women and Child Health, The Aga Khan University, Karachi 74800, Pakistan
- Centre for Global Child Health, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada
- Department of Nutritional Sciences, University of Toronto, Toronto, ON M5S 3E2, Canada
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25
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Robertson RC, Edens TJ, Carr L, Mutasa K, Gough EK, Evans C, Geum HM, Baharmand I, Gill SK, Ntozini R, Smith LE, Chasekwa B, Majo FD, Tavengwa NV, Mutasa B, Francis F, Tome J, Stoltzfus RJ, Humphrey JH, Prendergast AJ, Manges AR. The gut microbiome and early-life growth in a population with high prevalence of stunting. Nat Commun 2023; 14:654. [PMID: 36788215 PMCID: PMC9929340 DOI: 10.1038/s41467-023-36135-6] [Citation(s) in RCA: 34] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2022] [Accepted: 01/12/2023] [Indexed: 02/16/2023] Open
Abstract
Stunting affects one-in-five children globally and is associated with greater infectious morbidity, mortality and neurodevelopmental deficits. Recent evidence suggests that the early-life gut microbiome affects child growth through immune, metabolic and endocrine pathways. Using whole metagenomic sequencing, we map the assembly of the gut microbiome in 335 children from rural Zimbabwe from 1-18 months of age who were enrolled in the Sanitation, Hygiene, Infant Nutrition Efficacy Trial (SHINE; NCT01824940), a randomized trial of improved water, sanitation and hygiene (WASH) and infant and young child feeding (IYCF). Here, we show that the early-life gut microbiome undergoes programmed assembly that is unresponsive to the randomized interventions intended to improve linear growth. However, maternal HIV infection is associated with over-diversification and over-maturity of the early-life gut microbiome in their uninfected children, in addition to reduced abundance of Bifidobacterium species. Using machine learning models (XGBoost), we show that taxonomic microbiome features are poorly predictive of child growth, however functional metagenomic features, particularly B-vitamin and nucleotide biosynthesis pathways, moderately predict both attained linear and ponderal growth and growth velocity. New approaches targeting the gut microbiome in early childhood may complement efforts to combat child undernutrition.
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Affiliation(s)
- Ruairi C Robertson
- Blizard Institute, Queen Mary University of London, London, UK
- Microenvironment & Immunity Unit, INSERM U1224, Institut Pasteur, 75015, Paris, France
| | | | - Lynnea Carr
- Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada
| | - Kuda Mutasa
- Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe
| | - Ethan K Gough
- Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | - Ceri Evans
- Blizard Institute, Queen Mary University of London, London, UK
- Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe
| | - Hyun Min Geum
- School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada
| | - Iman Baharmand
- School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada
| | - Sandeep K Gill
- School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada
| | - Robert Ntozini
- Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe
| | - Laura E Smith
- Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe
- Department of Public and Ecosystem Health, Cornell University, Ithaca, NY, USA
| | - Bernard Chasekwa
- Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe
| | - Florence D Majo
- Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe
| | - Naume V Tavengwa
- Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe
| | - Batsirai Mutasa
- Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe
| | - Freddy Francis
- Department of Experimental Medicine, University of British Columbia, Vancouver, BC, Canada
| | - Joice Tome
- Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe
| | | | - Jean H Humphrey
- Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | - Andrew J Prendergast
- Blizard Institute, Queen Mary University of London, London, UK
- Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe
- Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | - Amee R Manges
- School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada.
- British Columbia Centre for Disease Control, Vancouver, BC, Canada.
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26
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Oldenburg CE, Hinterwirth A, Dah C, Millogo O, Coulibaly B, Ouedraogo M, Sié A, Chen C, Zhong L, Ruder K, Lebas E, Nyatigo F, Arnold BF, O’Brien KS, Doan T. Gut Microbiome among Children with Uncomplicated Severe Acute Malnutrition in a Randomized Controlled Trial of Azithromycin versus Amoxicillin. Am J Trop Med Hyg 2023; 108:206-211. [PMID: 36509053 PMCID: PMC9833071 DOI: 10.4269/ajtmh.22-0381] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Accepted: 09/25/2022] [Indexed: 12/15/2022] Open
Abstract
Antibiotics are routinely used as part of the management of severe acute malnutrition and are known to reduce gut microbial diversity in non-malnourished children. We evaluated gut microbiomes in children participating in a randomized controlled trial (RCT) of azithromycin versus amoxicillin for severe acute malnutrition. Three hundred one children aged 6 to 59 months with uncomplicated severe acute malnutrition (mid-upper arm circumference < 11.5 cm and/or weight-for-height Z-score < -3 without clinical complications) were enrolled in a 1:1 RCT of single-dose azithromycin versus a 7-day course of amoxicillin (standard of care). Of these, 109 children were randomly selected for microbiome evaluation at baseline and 8 weeks. Rectal swabs were processed with metagenomic DNA sequencing. We compared alpha diversity (inverse Simpson's index) at 8 weeks and evaluated relative abundance of microbial taxa using DESeq2. Of 109 children enrolled in the microbiome study, 95 were followed at 8 weeks. We found no evidence of a difference in alpha diversity between the azithromycin and amoxicillin groups at 8 weeks controlling for baseline diversity (mean difference -0.6, 95% CI -1.8 to 0.6, P = 0.30). Gut microbiomes did not diversify during the study. Differentially abundant genera at the P < 0.01 level included Salmonella spp. and Shigella spp., both of which were overabundant in the azithromycin compared with amoxicillin groups. We found no evidence to support an overall difference in gut microbiome diversity between azithromycin and amoxicillin among children with uncomplicated severe acute malnutrition, but potentially pathogenic bacteria that can cause invasive diarrhea were more common in the azithromycin group. Trial Registration: ClinicalTrials.gov NCT03568643.
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Affiliation(s)
- Catherine E. Oldenburg
- Francis I Proctor Foundation, University of California, San Francisco, California
- Department of Ophthalmology, University of California, San Francisco, California
- Department of Epidemiology & Biostatistics, University of California, San Francisco, California
- Institute for Global Health Sciences, University of California, San Francisco, California
| | - Armin Hinterwirth
- Francis I Proctor Foundation, University of California, San Francisco, California
| | - Clarisse Dah
- Centre de Recherche en Santé de Nouna, Nouna, Burkina Faso
| | | | | | | | - Ali Sié
- Centre de Recherche en Santé de Nouna, Nouna, Burkina Faso
| | - Cindi Chen
- Francis I Proctor Foundation, University of California, San Francisco, California
| | - Lina Zhong
- Francis I Proctor Foundation, University of California, San Francisco, California
| | - Kevin Ruder
- Francis I Proctor Foundation, University of California, San Francisco, California
| | - Elodie Lebas
- Francis I Proctor Foundation, University of California, San Francisco, California
| | - Fanice Nyatigo
- Francis I Proctor Foundation, University of California, San Francisco, California
| | - Benjamin F. Arnold
- Francis I Proctor Foundation, University of California, San Francisco, California
- Department of Ophthalmology, University of California, San Francisco, California
| | - Kieran S. O’Brien
- Francis I Proctor Foundation, University of California, San Francisco, California
- Department of Ophthalmology, University of California, San Francisco, California
| | - Thuy Doan
- Francis I Proctor Foundation, University of California, San Francisco, California
- Department of Ophthalmology, University of California, San Francisco, California
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27
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Theodorea CF, Diven S, Hendrawan D, Djais AA, Bachtiar BM, Widyarman AS, Seneviratne CJ. Characterization of Oral Veillonella Species in Dental Biofilms in Healthy and Stunted Groups of Children Aged 6-7 Years in East Nusa Tenggara. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:13998. [PMID: 36360876 PMCID: PMC9656475 DOI: 10.3390/ijerph192113998] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Revised: 10/21/2022] [Accepted: 10/25/2022] [Indexed: 06/16/2023]
Abstract
Impaired development that causes stunting is one of the most common health problems in Indonesia. In particular, the highest number of cases of stunting in Indonesia was reported in the East Nusa Tenggara (NTT) province. Previous studies have shown a tendency for deteriorating oral hygiene in children with a poor nutritional status. In addition, a higher proportion of oral Veillonella has been reported in children with poor oral hygiene. However, the relationship between populations of oral Veillonella and stunting has not been studied before. Therefore, this study aimed to analyze the oral Veillonella profile in the dental biofilms of healthy and stunted children aged 6-7 years. The participants were 60 elementary school students in the Nangapanda District, Ende, NTT, Indonesia. In this study, real-time polymerase chain reaction was used to examine dental biofilm samples from the healthy (n = 31) and stunted (n = 29) groups. The results revealed that seven oral Veillonella species were found in all groups. However, the number of four oral Veillonella species significantly differed between the healthy and stunted groups: V. denticariosi, V. infantium, V. rogosae, and V. tobetsuensis. This is the first study to demonstrate a potential association between oral Veillonella species and stunting in children.
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Affiliation(s)
- Citra Fragrantia Theodorea
- Department of Oral Biology, Faculty of Dentistry, Universitas Indonesia, Jalan Salemba Raya No. 4, Central Jakarta 10430, Indonesia
| | - Saint Diven
- Undergraduate Program, Faculty of Dentistry, Universitas Indonesia, Jalan Salemba Raya No. 4, Jakarta 10430, Indonesia
| | - Devin Hendrawan
- Undergraduate Program, Faculty of Dentistry, Universitas Indonesia, Jalan Salemba Raya No. 4, Jakarta 10430, Indonesia
| | - Ariadna Adisattya Djais
- Department of Oral Biology, Faculty of Dentistry, Universitas Indonesia, Jalan Salemba Raya No. 4, Central Jakarta 10430, Indonesia
| | - Boy Muchlis Bachtiar
- Department of Oral Biology, Faculty of Dentistry, Universitas Indonesia, Jalan Salemba Raya No. 4, Central Jakarta 10430, Indonesia
| | - Armelia Sari Widyarman
- Department of Microbiology, Faculty of Dentistry, Trisakti University, Jalan Kyai Tapa No. 1, West Jakarta 11440, Indonesia
| | - Chaminda Jayampath Seneviratne
- National Dental Research Institute Singapore, National Dental Centre Singapore, Singapore 168938, Singapore
- Oral Health Academic Clinical Programme, Duke-NUS Graduate Medical School, Singapore 169857, Singapore
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28
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Stunted children display ectopic small intestinal colonization by oral bacteria, which cause lipid malabsorption in experimental models. Proc Natl Acad Sci U S A 2022; 119:e2209589119. [PMID: 36197997 PMCID: PMC9573096 DOI: 10.1073/pnas.2209589119] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
Environmental enteric dysfunction (EED) is an inflammatory syndrome postulated to contribute to stunted child growth and to be associated with intestinal dysbiosis and nutrient malabsorption. However, the small intestinal contributions to EED remain poorly understood. This study aimed to assess changes in the proximal and distal intestinal microbiota in the context of stunting and EED and to test for a causal role of these bacterial isolates in the underlying pathophysiology. We performed a cross-sectional study in two African countries recruiting roughly 1,000 children aged 2 to 5 years and assessed the microbiota in the stomach, duodenum, and feces. Upper gastrointestinal samples were obtained from stunted children and stratified according to stunting severity. Fecal samples were collected. We then investigated the role of clinical isolates in EED pathophysiology using tissue culture and animal models. We find that small intestinal bacterial overgrowth (SIBO) is extremely common (>80%) in stunted children. SIBO is frequently characterized by an overgrowth of oral bacteria, leading to increased permeability and inflammation and to replacement of classical small intestinal strains. These duodenal bacterial isolates decrease lipid absorption in both cultured enterocytes and mice, providing a mechanism by which they may exacerbate EED and stunting. Further, we find a specific fecal signature associated with the EED markers fecal calprotectin and alpha-antitrypsin. Our study shows a causal implication of ectopic colonization of oral bacterial isolated from the small intestine in nutrient malabsorption and gut leakiness in vitro. These findings have important therapeutic implications for modulating the microbiota through microbiota-targeted interventions.
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29
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Haj Ali S, Abu Sneineh A, Hasweh R. Nutritional assessment in patients with liver cirrhosis. World J Hepatol 2022; 14:1694-1703. [PMID: 36185724 PMCID: PMC9521456 DOI: 10.4254/wjh.v14.i9.1694] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Revised: 08/09/2022] [Accepted: 09/09/2022] [Indexed: 02/06/2023] Open
Abstract
Malnutrition is a liver cirrhosis complication affecting more than 20%-50% of patients. Although the term can refer to either nutrient deficiency or excess, it usually relates to undernutrition in cirrhosis settings. Frailty is defined as limited physical function due to muscle weakness, whereas sarcopenia is defined as muscle mass loss and an advanced malnutrition stage. The pathogenesis of malnutrition in liver cirrhosis is multifactorial, including decreased oral intake, maldigestion/malabsorption, physical inactivity, hyperammonemia, hypermetabolism, altered macronutrient metabolism and gut microbiome dysbiosis. Patients with chronic liver disease with a Body Mass Index of < 18.5 kg/m2 and/or decompensated cirrhosis or Child-Pugh class C are at the highest risk of malnutrition. For patients at risk of malnutrition, a detailed nutritional assessment is required, typically including a history and physical examination, laboratory testing, global assessment tools and body composition testing. The latter can be done using anthropometry, cross-sectional imaging including computed tomography or magnetic resonance, bioelectrical impedance analysis and dual-energy X-ray absorptiometry. A multidisciplinary team should screen for and treat malnutrition in patients with cirrhosis. Malnutrition and sarcopenia are associated with an increased risk of complications and a poor prognosis in patients with liver cirrhosis; thus, it is critical to diagnose these conditions early and initiate the appropriate nutritional therapy. In this review, we describe the prevalence and pathogenesis of malnutrition in liver cirrhosis patients and discuss the best diagnostic approach to nutritional assessment for them.
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Affiliation(s)
- Sara Haj Ali
- Department of Internal Medicine, Faculty of Medicine, Al-Balqa Applied University, Salt 19117, Jordan
| | - Awni Abu Sneineh
- Department of Gastroenterology and Hepatology, University of Jordan, Faculty of Medicine, Amman 11942, Jordan
| | - Reem Hasweh
- Department of Internal Medicine, Faculty of Medicine, Al-Balqa Applied University, Salt 19117, Jordan
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30
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Eslabão LB, Gubert GF, Beltrame LC, Mello IMA, Bruna-Romero O, Zárate-Bladés CR. Prophylactic Treatment of Undernourished Mice with Cotrimoxazole Induces a Different Profile of Dysbiosis with Functional Metabolic Alterations. Cells 2022; 11:cells11152278. [PMID: 35892575 PMCID: PMC9331864 DOI: 10.3390/cells11152278] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Revised: 07/12/2022] [Accepted: 07/16/2022] [Indexed: 02/01/2023] Open
Abstract
Childhood malnutrition affects physiology and development. It increases infection rates, which may not present clinical signs in severe cases. The World Health Organization recommends prophylactic treatment with cotrimoxazole (SXT) and nutritional recovery to overcome this issue. This treatment is controversial, since evidence of a reduction in morbidity and mortality is not a consensus and could induce the development of antibiotic-resistant bacteria. Moreover, the impact of using this wide-spectrum antibiotic on gut microbiota in a critical period of development, and weakness is unknown. To understand how SXT prophylaxis could affect gut microbiota in undernutrition, we induced protein–energy undernutrition (PEU) in weaning C57BL/6 mice for three weeks and treated animals with SXT for two weeks. Using 16S rRNA gene sequencing, we compared the taxonomic composition and metabolic pathways of control mice, animals submitted to undernutrition (UND), treated with SXT, or undernourished and SXT treated (UND + SXT). We identified that UND mice had a significant increase in predicted pathways related to metabolic syndromes later in life. The prophylactic SXT treatment alone resulted in a significant loss in community richness and beta diversity. Furthermore, we identified the reduction of three genera in SXT treated mice, including the butyrate producers Faecalibacterium and Anaerotruncus. Both UND and double challenge (UND + SXT) resulted in a reduction of the amino acid’s biosynthesis pathway related to cell growth. Our results show that the SXT prophylaxis of young mice during an undernourishment period did not re-establish the undernourished microbiota community composition similar to healthy controls but induced a distinct dysbiotic profile with functional metabolic consequences.
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Affiliation(s)
- Lívia Budziarek Eslabão
- Laboratório de Imunorregulação, iREG, Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de Santa Catarina, Campus Universitário da Trindade, Florianópolis 88034-040, SC, Brazil; (L.B.E.); (G.F.G.); (L.C.B.); (I.M.A.M.)
- Laboratório de Imunologia Aplicada, Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de Santa Catarina, Campus Universitário da Trindade, Florianópolis 88034-040, SC, Brazil
| | - Gabriela Farias Gubert
- Laboratório de Imunorregulação, iREG, Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de Santa Catarina, Campus Universitário da Trindade, Florianópolis 88034-040, SC, Brazil; (L.B.E.); (G.F.G.); (L.C.B.); (I.M.A.M.)
| | - Lucas Cafferati Beltrame
- Laboratório de Imunorregulação, iREG, Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de Santa Catarina, Campus Universitário da Trindade, Florianópolis 88034-040, SC, Brazil; (L.B.E.); (G.F.G.); (L.C.B.); (I.M.A.M.)
| | - Isis M. A. Mello
- Laboratório de Imunorregulação, iREG, Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de Santa Catarina, Campus Universitário da Trindade, Florianópolis 88034-040, SC, Brazil; (L.B.E.); (G.F.G.); (L.C.B.); (I.M.A.M.)
| | - Oscar Bruna-Romero
- Laboratório de Imunologia Aplicada, Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de Santa Catarina, Campus Universitário da Trindade, Florianópolis 88034-040, SC, Brazil
- Correspondence: (O.B.-R.); (C.R.Z.-B.); Tel.: +55-48-37215210 (C.R.Z.-B.)
| | - Carlos R. Zárate-Bladés
- Laboratório de Imunorregulação, iREG, Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de Santa Catarina, Campus Universitário da Trindade, Florianópolis 88034-040, SC, Brazil; (L.B.E.); (G.F.G.); (L.C.B.); (I.M.A.M.)
- Correspondence: (O.B.-R.); (C.R.Z.-B.); Tel.: +55-48-37215210 (C.R.Z.-B.)
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Panigrahi MK, Kaliaperumal V, Akella A, Venugopal G, Ramadass B. Mapping microbiome-redox spectrum and evaluating Microbial-Redox Index in chronic gastritis. Sci Rep 2022; 12:8450. [PMID: 35589904 PMCID: PMC9120160 DOI: 10.1038/s41598-022-12431-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Accepted: 05/11/2022] [Indexed: 12/27/2022] Open
Abstract
Peptic ulcer disease (PUD) and chronic gastritis are prevalent in developing countries. The role of oxidative stress in the pathogenesis of gastrointestinal mucosal disorders is well recognized. In PUD, the gastric mucosa and its associated microbiome are subject to diet and stress-induced oxidative perturbations. Tissue redox potential (ORP) measurement can quantify oxidative stress, reflecting the balance between prooxidants and antioxidants. This study hypothesizes that the oxidative stress quantified by tissue ORP will be associated with characteristic changes in the mucosa-associated microbiome in PUD and gastritis. In addition, we propose using relative microbial abundance as a quantitative marker of mucosal health. Endoscopy was performed to obtain gastric mucosal biopsies from ten PUD and ten non-ulcer dyspepsia (NUD) patients. The tissue ORP was measured directly with a microelectrode using a biopsy specimen. A second specimen from an adjacent site was subjected to 16s rRNA gene sequencing. From the OTUs, the relative abundance of the microbial taxon in each of the samples was derived. We analyzed the genome of the predominant species for genes encoding the utilization of oxygen as an electron acceptor in respiration and for the presence of antioxidant defense mechanisms. The organisms were then grouped based on their established and inferred redox traits. Shannon diversity index and Species richness were calculated on rarefied data. The relative abundance of organisms that prefer high ORP over those that favor low ORP is conceived as the “Microbial Redox Index (MRI),” an indicator of mucosal health. In the gastric mucosa, aerobic species predominate and are more diverse than the anaerobes. The predominant aerobes are Helicobacter pylori and Sphingobacterium mizutaii. The abundance of these two species had an inverse correlation with the abundance of low ORP preferring anaerobes. Their relative abundance ratio (Microbial Redox Index) correlated with the tissue oxidation–reduction potential (ORP), a direct measure of oxidative stress. Correlation analysis also revealed that the abundance of all anaerobes inversely correlated with the dominant aerobic taxa. In addition, Shannon and Species richness diversity indices, the probable indicators of mucosal health, were negatively correlated with Microbial Redox Index. Using PUD as a prototype mucosal disease, this article describes a generalized approach to infer and quantify mucosal oxidative stress by analyzing the relative abundance of microorganisms that preferentially grow at the extremes of the tissue redox potential. This ratiometric Microbial Redox Index can also be assessed using simple qPCR without the need for sequencing. The approach described herein may be helpful as a widely applicable quantitative measure of mucosal health with prognostic and therapeutic implications.
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Affiliation(s)
- Manas Kumar Panigrahi
- Department of Gastroenterology, All India Institute of Medical Sciences, Bhubaneswar, India
| | - Venkatesh Kaliaperumal
- MYAS-NIN Department of Sports Science, ICMR-National Institute of Nutrition, Hyderabad, India
| | - Abhishek Akella
- Center of Excellence for Clinical Microbiome Research, All India Institute of Medical Sciences, Bhubaneswar, 751019, India
| | - Giriprasad Venugopal
- Center of Excellence for Clinical Microbiome Research, All India Institute of Medical Sciences, Bhubaneswar, 751019, India
| | - Balamurugan Ramadass
- Center of Excellence for Clinical Microbiome Research, All India Institute of Medical Sciences, Bhubaneswar, 751019, India. .,Department of Biochemistry, All India Institute of Medical Sciences, Bhubaneswar, India.
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Kamil RZ, Murdiati A, Juffrie M, Rahayu ES. Gut Microbiota Modulation of Moderate Undernutrition in Infants through Gummy Lactobacillus plantarum Dad-13 Consumption: A Randomized Double-Blind Controlled Trial. Nutrients 2022; 14:1049. [PMID: 35268024 PMCID: PMC8912314 DOI: 10.3390/nu14051049] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Revised: 02/10/2022] [Accepted: 02/25/2022] [Indexed: 01/03/2023] Open
Abstract
Undernutrition is associated with gut microbiota unbalance, and probiotics are believed to restore it and improve gut integrity. A randomized double-blind controlled trial was conducted to evaluate the efficacy of gummy L. plantarum Dad-13 (108-9 CFU/3 g) to prevent the progression of severe undernutrition. Two groups of moderate undernutrition infants were involved in this study, namely the placebo (n = 15) and probiotics (n = 15) groups, and were required to consume the product for 50 days. 16S rRNA sequencing and qPCR were used for gut microbiota analysis, and gas chromatography was used to analyze Short-Chain Fatty Acid (SCFA). The daily food intake of both groups was recorded using food records. Our results revealed that the probiotic group had better improvements regarding the anthropometry and nutritional status. In addition, L. plantarum Dad-13 modulated the butyric acid-producing bacteria to increase and inhibit the growth of Enterobacteriaceae. This gut modulation was associated with the increment in SCFA, especially total SCFA, propionic, and butyric acid. The number of L. plantarum was increased after the probiotic intervention. However, L. plantarum Dad-13 was not able to change the alpha and beta diversity. Therefore, L. plantarum Dad-13 has been proven to promote the growth of beneficial bacteria.
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Affiliation(s)
- Rafli Zulfa Kamil
- Department of Food and Agricultural Product Technology, Faculty of Agricultural Technology, Universitas Gadjah Mada, Jl. Flora No 1 Bulaksumur, Yogyakarta 55281, Indonesia; (R.Z.K.); (A.M.)
- Centre for Food and Nutrition Studies, Universitas Gadjah Mada, Jl. Teknika Utara Barek, Yogyakarta 55281, Indonesia
- Centre of Excellence for Probiotics, Universitas Gadjah Mada, Jl. Teknika Utara Barek, Yogyakarta 55281, Indonesia
- Department of Food Technology, Faculty of Animal and Agricultural Sciences, Universitas Diponegoro, Jl. Prof. Soedarto, Tembalang, Semarang 50275, Indonesia
| | - Agnes Murdiati
- Department of Food and Agricultural Product Technology, Faculty of Agricultural Technology, Universitas Gadjah Mada, Jl. Flora No 1 Bulaksumur, Yogyakarta 55281, Indonesia; (R.Z.K.); (A.M.)
| | - Mohammad Juffrie
- Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Jl. Farmako, Senolowo, Sekip Utara, Yogyakarta 55281, Indonesia;
| | - Endang Sutriswati Rahayu
- Department of Food and Agricultural Product Technology, Faculty of Agricultural Technology, Universitas Gadjah Mada, Jl. Flora No 1 Bulaksumur, Yogyakarta 55281, Indonesia; (R.Z.K.); (A.M.)
- Centre for Food and Nutrition Studies, Universitas Gadjah Mada, Jl. Teknika Utara Barek, Yogyakarta 55281, Indonesia
- Centre of Excellence for Probiotics, Universitas Gadjah Mada, Jl. Teknika Utara Barek, Yogyakarta 55281, Indonesia
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Kortekangas E, Fan YM, Chaima D, Lehto KM, Malamba-Banda C, Matchado A, Chingwanda C, Liu Z, Ashorn U, Cheung YB, Dewey KG, Maleta K, Ashorn P. Associations between Gut Microbiota and Intestinal Inflammation, Permeability and Damage in Young Malawian Children. J Trop Pediatr 2022; 68:6527323. [PMID: 35149871 PMCID: PMC8846364 DOI: 10.1093/tropej/fmac012] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Environmental enteric dysfunction (EED) is common in low- and middle-income countries and associated with childhood undernutrition. The composition of gut microbiota has been implicated in the pathogenesis of EED. Our aim was to assess the associations between gut microbiota and EED biomarkers in rural Malawian children. We hypothesized that there would be an inverse association between microbiota maturity and diversity and fecal concentrations of EED biomarkers. METHODS We used data from fecal samples collected at 6, 18 and 30 months from 611 children who were followed up during a nutrition intervention trial. The primary time point for analysis was 18 months. Microbiota data were obtained through 16S rRNA sequencing and variables included microbiota maturity and diversity, phylogenetic dissimilarity and relative abundances of individual taxa. EED biomarkers included calprotectin (marker of inflammation), alpha-1 antitrypsin (intestinal permeability) and REG1B (intestinal damage). RESULTS There was an inverse association between microbiota maturity and diversity and fecal concentrations of all 3 EED biomarkers at 18 months (p≤0.001). The results were similar at 30 months, while at 6 months inverse associations were found only with calprotectin and alpha-1 antitrypsin concentrations. At 18 months, EED biomarkers were not associated with phylogenetic dissimilarity, but at 6 and 30 months several associations were observed. Individual taxa predicting EED biomarker concentrations at 18 months included several Bifidobacterium and Enterobacteriaceae taxa as well as potentially displaced oral taxa. CONCLUSIONS Our findings support the hypothesis of an inverse association between microbiota maturity and diversity and EED in rural Malawian children.
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Affiliation(s)
- Emma Kortekangas
- Center for Child, Adolescent and Maternal Health Research, Faculty of Medicine and Health Technology, Tampere University, Tampere 33014, Finland,Correspondence: Emma Kortekangas, Tampere Center for Child, Adolescent and Maternal Health Research, Faculty of Medicine and Health Technology, Global Health, Tampere University, Arvo Ylpön katu 34, Arvo building, Tampere 33014, Finland. Tel: +358-3-355-111. Fax +358-3-213-4473. E-mail <>
| | - Yue-Mei Fan
- Center for Child, Adolescent and Maternal Health Research, Faculty of Medicine and Health Technology, Tampere University, Tampere 33014, Finland
| | - David Chaima
- School of Public Health and Family Medicine, College of Medicine, University of Malawi, Blantyre, Malawi
| | - Kirsi-Maarit Lehto
- Center for Child, Adolescent and Maternal Health Research, Faculty of Medicine and Health Technology, Tampere University, Tampere 33014, Finland
| | - Chikondi Malamba-Banda
- School of Public Health and Family Medicine, College of Medicine, University of Malawi, Blantyre, Malawi
| | - Andrew Matchado
- School of Public Health and Family Medicine, College of Medicine, University of Malawi, Blantyre, Malawi,Department of Nutrition and Institute for Global Nutrition, University of California Davis, Davis, CA 95616, USA
| | - Chilungamo Chingwanda
- School of Public Health and Family Medicine, College of Medicine, University of Malawi, Blantyre, Malawi
| | - Zhifei Liu
- Center for Child, Adolescent and Maternal Health Research, Faculty of Medicine and Health Technology, Tampere University, Tampere 33014, Finland
| | - Ulla Ashorn
- Center for Child, Adolescent and Maternal Health Research, Faculty of Medicine and Health Technology, Tampere University, Tampere 33014, Finland
| | - Yin Bun Cheung
- Program in Health Services & Systems Research and Centre for Quantitative Medicine, Duke-NUS Medical School, Singapore 169857, Singapore
| | - Kathryn G Dewey
- Department of Nutrition and Institute for Global Nutrition, University of California Davis, Davis, CA 95616, USA
| | - Kenneth Maleta
- School of Public Health and Family Medicine, College of Medicine, University of Malawi, Blantyre, Malawi
| | - Per Ashorn
- Center for Child, Adolescent and Maternal Health Research, Faculty of Medicine and Health Technology, Tampere University, Tampere 33014, Finland,Department of Pediatrics, Tampere University Hospital, Tampere 33520, Finland
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The Mediating Role of the Gut Microbiota in the Physical Growth of Children. Life (Basel) 2022; 12:life12020152. [PMID: 35207440 PMCID: PMC8880549 DOI: 10.3390/life12020152] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2021] [Revised: 01/18/2022] [Accepted: 01/19/2022] [Indexed: 12/12/2022] Open
Abstract
Gut microbiota succession overlaps with intensive growth in infancy and early childhood. The multitude of functions performed by intestinal microbes, including participation in metabolic, hormonal, and immune pathways, makes the gut bacterial community an important player in cross-talk between intestinal processes and growth. Long-term disturbances in the colonization pattern may affect the growth trajectory, resulting in stunting or wasting. In this review, we summarize the evidence on the mediating role of gut microbiota in the mechanisms controlling the growth of children.
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Gut microbiome dysbiosis in malnutrition. PROGRESS IN MOLECULAR BIOLOGY AND TRANSLATIONAL SCIENCE 2022; 192:205-229. [DOI: 10.1016/bs.pmbts.2022.07.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
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Wallenborn JT, Vonaesch P. OUP accepted manuscript. Gastroenterol Rep (Oxf) 2022; 10:goac010. [PMID: 35419206 PMCID: PMC8996373 DOI: 10.1093/gastro/goac010] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2021] [Revised: 12/10/2021] [Accepted: 02/16/2022] [Indexed: 11/15/2022] Open
Abstract
The intestinal microbiota plays a crucial role in health and changes in its composition are linked with major global human diseases. Fully understanding what shapes the human intestinal microbiota composition and knowing ways of modulating the composition are critical for promotion of life-course health, combating diseases, and reducing global health disparities. We aim to provide a foundation for understanding what shapes the human intestinal microbiota on an individual and global scale, and how interventions could utilize this information to promote life-course health and reduce global health disparities. We briefly review experiences within the first 1,000 days of life and how long-term exposures to environmental elements or geographic specific cultures have lasting impacts on the intestinal microbiota. We also discuss major public health threats linked to the intestinal microbiota, including antimicrobial resistance and disappearing microbial diversity due to globalization. In order to promote global health, we argue that the interplay of the larger ecosystem with intestinal microbiota research should be utilized for future research and urge for global efforts to conserve microbial diversity.
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Affiliation(s)
- Jordyn T Wallenborn
- Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland
- University of Basel, Basel, Switzerland
| | - Pascale Vonaesch
- Department of Fundamental Microbiology, University of Lausanne, Bâtiment Biophore Campus UNIL-Sorge, Lausanne, Switzerland
- Corresponding author. Department of Fundamental Microbiology, University of Lausanne, 1015 Lausanne, Switzerland. Tel: +41-21-692-5600;
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Gunawan D, Juffrie M, Helmyati S, Rahayu ES. Effect of Lactobacillus plantarum DAD-13 and Fructo-oligosaccharides on Short-Chain Fatty Acid Profile and Nutritional Status in Indonesian Stunting Children. Open Access Maced J Med Sci 2021. [DOI: 10.3889/oamjms.2021.7903] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
BACKGROUND: Chronic gut inflammation is a generalized disturbance of small intestine structure and function is likely to play a large role in the incidence of stunting. It will be disturbances the absorption of nutrients, therefore, it can indirectly reduce on nutritional status.
AIM: The aim of this study is to examine the effect of Lactobacillus plantarum DAD-13 and fructooligosaccharide on short-chain fatty acid (SCFA) profile and nutritional status in Indonesian stunting children.
METHODS: The study design was used double-blind randomized placebo-controlled trial, 39 stunting children under five received daily oral supplementations of L. plantarum DAD-13 1 × 1010 cfu and fructooligosaccharide 700 mg (symbiotic group) or placebo group for 90 days. SCFA profile was analyzed using gas chromatography and nutritional status was assessed by WAZ, HAZ, and WHZ.
RESULTS: The result shows in symbiotic and control group, the mean age was 26 ± 8.34 and 29 ± 5.78, and the mean weight was 8.5 ± 0.94 kg and 9.0 ± 0.82 kg, while the mean height was 78.96 ± 5.4 cm and 80.9 ± 4.55 cm, respectively. Concentrations of acetate, propionate, and butyrate in the symbiotic group after consumption were 17.10 ± 2.97, 7.70 ± 2.05, and 7.47 ± 1.76 while in placebo group 12.44 ± 3.61, 5.20 ± 1.66, and 6.12 ± 1.16, respectively. There was a significant difference in the mean SCFA concentration between the symbiotic and placebo groups (p < 0.05), where the SCFA concentration in the symbiotic group was significantly higher than the placebo group. Nutritional status (WAZ, HAZ, and WHZ) was observed significantly in symbiotic group (p < 0.05), only on WHZ has cutoff point >-2SD after the intervention, while WAZ and HAZ <-2SD.
CONCLUSIONS: L. plantarum DAD-13 and fructooligosaccharide 90 days supplementation have increase acetate, butyrate, and propionate that are important fuels for intestinal epithelial cells that can play an important role in the maintenance of health.
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Kalia VC, Gong C, Shanmugam R, Lin H, Zhang L, Lee JK. The Emerging Biotherapeutic Agent: Akkermansia. Indian J Microbiol 2021; 62:1-10. [PMID: 34931096 PMCID: PMC8674859 DOI: 10.1007/s12088-021-00993-9] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2021] [Accepted: 12/02/2021] [Indexed: 12/17/2022] Open
Abstract
The human gastrointestinal tract (GIT) is a well-recognized hub of microbial activities. The microbiota harboring the mucus layer of the GIT act as a defense against noxious substances, and pathogens including Clostridium difficile, Enterococcus faecium, Escherichia coli, Salmonella Typhimurium. Toxins, pathogens, and antibiotics perturb the commensal floral composition within the GIT. Imbalanced gut microbiota leads to dysbiosis, manifested as diseases ranging from obesity, diabetes, and cancer to reduced lifespan. Among the bacteria present in the gut microbiome, the most beneficial are those representing Firmicutes and Bacteroidetes. Recent studies have revealed the emergence of a novel biotherapeutic agent, Akkermansia, which is instrumental in regaining eubiosis and conferring various health benefits.
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Affiliation(s)
- Vipin Chandra Kalia
- Department of Chemical Engineering, Konkuk University, 1 Hwayang-Dong, Gwangjin-Gu, Seoul, 05029 Republic of Korea
| | - Chunjie Gong
- National “111” Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei University of Technology, Wuhan, 430068 People’s Republic of China
| | - Ramasamy Shanmugam
- Department of Chemical Engineering, Konkuk University, 1 Hwayang-Dong, Gwangjin-Gu, Seoul, 05029 Republic of Korea
| | - Hui Lin
- College of Life Sciences, Gutian Edible Fungi Research Institute, Fujian Agriculture and Forestry University, Fuzhou, 350002 People’s Republic of China
| | - Liaoyuan Zhang
- College of Life Sciences, Gutian Edible Fungi Research Institute, Fujian Agriculture and Forestry University, Fuzhou, 350002 People’s Republic of China
| | - Jung-Kul Lee
- Department of Chemical Engineering, Konkuk University, 1 Hwayang-Dong, Gwangjin-Gu, Seoul, 05029 Republic of Korea
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Nothaft H, Perez-Muñoz ME, Yang T, Murugan AVM, Miller M, Kolarich D, Plastow GS, Walter J, Szymanski CM. Improving Chicken Responses to Glycoconjugate Vaccination Against Campylobacter jejuni. Front Microbiol 2021; 12:734526. [PMID: 34867850 PMCID: PMC8637857 DOI: 10.3389/fmicb.2021.734526] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Accepted: 10/04/2021] [Indexed: 01/03/2023] Open
Abstract
Campylobacter jejuni is a common cause of diarrheal disease worldwide. Human infection typically occurs through the ingestion of contaminated poultry products. We previously demonstrated that an attenuated Escherichia coli live vaccine strain expressing the C. jejuni N-glycan on its surface reduced the Campylobacter load in more than 50% of vaccinated leghorn and broiler birds to undetectable levels (responder birds), whereas the remainder of the animals was still colonized (non-responders). To understand the underlying mechanism, we conducted three vaccination and challenge studies using 135 broiler birds and found a similar responder/non-responder effect. Subsequent genome-wide association studies (GWAS), analyses of bird sex and levels of vaccine-induced IgY responses did not correlate with the responder versus non-responder phenotype. In contrast, antibodies isolated from responder birds displayed a higher Campylobacter-opsonophagocytic activity when compared to antisera from non-responder birds. No differences in the N-glycome of the sera could be detected, although minor changes in IgY glycosylation warrant further investigation. As reported before, the composition of the microbiota, particularly levels of OTU classified as Clostridium spp., Ruminococcaceae and Lachnospiraceae are associated with the response. Transplantation of the cecal microbiota of responder birds into new birds in combination with vaccination resulted in further increases in vaccine-induced antigen-specific IgY responses when compared to birds that did not receive microbiota transplants. Our work suggests that the IgY effector function and microbiota contribute to the efficacy of the E. coli live vaccine, information that could form the basis for the development of improved vaccines targeted at the elimination of C. jejuni from poultry.
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Affiliation(s)
- Harald Nothaft
- Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB, Canada
| | - Maria Elisa Perez-Muñoz
- Department of Agricultural, Food & Nutritional Science, University of Alberta, Edmonton, AB, Canada
| | - Tianfu Yang
- Department of Agricultural, Food & Nutritional Science, University of Alberta, Edmonton, AB, Canada
| | - Abarna V M Murugan
- Institute for Glycomics, Griffith University, Gold Coast Campus, Southport, QLD, Australia
| | | | - Daniel Kolarich
- Institute for Glycomics, Griffith University, Gold Coast Campus, Southport, QLD, Australia.,ARC Centre of Excellence for Nanoscale BioPhotonics, Griffith University, Southport, QLD, Australia
| | - Graham S Plastow
- Department of Agricultural, Food & Nutritional Science, University of Alberta, Edmonton, AB, Canada.,Livestock Gentec, Edmonton, AB, Canada
| | - Jens Walter
- Department of Agricultural, Food & Nutritional Science, University of Alberta, Edmonton, AB, Canada
| | - Christine M Szymanski
- Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB, Canada.,Department of Microbiology and Complex Carbohydrate Research Center, University of Georgia, Athens, GA, United States
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40
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Huus KE, Hoang TT, Creus-Cuadros A, Cirstea M, Vogt SL, Knuff-Janzen K, Sansonetti PJ, Vonaesch P, Finlay BB. Cross-feeding between intestinal pathobionts promotes their overgrowth during undernutrition. Nat Commun 2021; 12:6860. [PMID: 34824233 PMCID: PMC8617199 DOI: 10.1038/s41467-021-27191-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Accepted: 11/08/2021] [Indexed: 12/18/2022] Open
Abstract
Child undernutrition is a global health issue associated with a high burden of infectious disease. Undernourished children display an overabundance of intestinal pathogens and pathobionts, and these bacteria induce enteric dysfunction in undernourished mice; however, the cause of their overgrowth remains poorly defined. Here, we show that disease-inducing human isolates of Enterobacteriaceae and Bacteroidales spp. are capable of multi-species symbiotic cross-feeding, resulting in synergistic growth of a mixed community in vitro. Growth synergy occurs uniquely under malnourished conditions limited in protein and iron: in this context, Bacteroidales spp. liberate diet- and mucin-derived sugars and Enterobacteriaceae spp. enhance the bioavailability of iron. Analysis of human microbiota datasets reveals that Bacteroidaceae and Enterobacteriaceae are strongly correlated in undernourished children, but not in adequately nourished children, consistent with a diet-dependent growth synergy in the human gut. Together these data suggest that dietary cross-feeding fuels the overgrowth of pathobionts in undernutrition.
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Affiliation(s)
- K. E. Huus
- grid.17091.3e0000 0001 2288 9830Michael Smith Laboratories and Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC Canada
| | - T. T. Hoang
- grid.17091.3e0000 0001 2288 9830Michael Smith Laboratories and Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC Canada
| | - A. Creus-Cuadros
- grid.17091.3e0000 0001 2288 9830Michael Smith Laboratories and Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC Canada
| | - M. Cirstea
- grid.17091.3e0000 0001 2288 9830Michael Smith Laboratories and Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC Canada
| | - S. L. Vogt
- grid.17091.3e0000 0001 2288 9830Michael Smith Laboratories and Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC Canada
| | - K. Knuff-Janzen
- grid.17091.3e0000 0001 2288 9830Michael Smith Laboratories and Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC Canada
| | - P. J. Sansonetti
- grid.428999.70000 0001 2353 6535Unité de Pathogénie Microbienne Moléculaire, Institut Pasteur, Paris, France ,grid.429007.80000 0004 0627 2381Present Address: Center for Microbes, Development and Health, Institut Pasteur de Shanghai, Shanghai, China
| | - P. Vonaesch
- grid.428999.70000 0001 2353 6535Unité de Pathogénie Microbienne Moléculaire, Institut Pasteur, Paris, France ,grid.416786.a0000 0004 0587 0574Present Address: Human and Animal Health Unit, Swiss Tropical and Public Health Institute & University of Basel, Basel, Switzerland
| | - B. B. Finlay
- grid.17091.3e0000 0001 2288 9830Michael Smith Laboratories and Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC Canada ,grid.440050.50000 0004 0408 2525Canadian Institute for Advanced Research, Toronto, Ontario Canada
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41
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Nothaft H, Bian X, Shajahan A, Miller WG, Bolick DT, Guerrant RL, Azadi P, Ng KKS, Szymanski CM. Detecting Glucose Fluctuations in the Campylobacter jejuni N-Glycan Structure. ACS Chem Biol 2021; 16:2690-2701. [PMID: 34726367 DOI: 10.1021/acschembio.1c00498] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Campylobacter jejuni is a significant cause of human gastroenteritis worldwide, and all strains express an N-glycan that is added to at least 80 different proteins. We characterized 98 C. jejuni isolates from infants from 7 low- and middle-income countries and identified 4 isolates unreactive with our N-glycan-specific antiserum that was raised against the C. jejuni heptasaccharide composed of GalNAc-GalNAc-GalNAc(Glc)-GalNAc-GalNAc-diNAcBac. Mass spectrometric analyses indicated these isolates express a hexasaccharide lacking the glucose branch. Although all 4 strains encode the PglI glucosyltransferase (GlcTF), one aspartate in the DXDD motif was missing, an alteration also present in ∼4% of all available PglI sequences. Deleting this residue from an active PglI resulted in a nonfunctional GlcTF when the protein glycosylation system was reconstituted in E. coli, while replacement with Glu/Ala was not deleterious. Molecular modeling proposed a mechanism for how the DXDD residues and the structure/length beyond the motif influence activity. Mouse vaccination with an E. coli strain expressing the full-length heptasaccharide produced N-glycan-specific antibodies and a corresponding reduction in Campylobacter colonization and weight loss following challenge. However, the antibodies did not recognize the hexasaccharide and were unable to opsonize C. jejuni isolates lacking glucose, suggesting this should be considered when designing N-glycan-based vaccines to prevent campylobacteriosis.
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Affiliation(s)
- Harald Nothaft
- Department of Medical Microbiology and Immunology, University of Alberta, Katz Group Centre, Edmonton, Alberta T6G 2E9, Canada
| | - Xiaoming Bian
- Department of Microbiology, University of Georgia, 527 Biological Sciences Building, Athens, Georgia 30602, United States
- Complex Carbohydrate Research Center, University of Georgia, 315 Riverbend Road, Athens, Georgia 30602, United States
| | - Asif Shajahan
- Complex Carbohydrate Research Center, University of Georgia, 315 Riverbend Road, Athens, Georgia 30602, United States
| | - William G. Miller
- Produce Safety and Microbiology Research Unit, Agricultural Research Service, United States Department of Agriculture, 800 Buchanan Street, Albany, California 94710, United States
| | - David T. Bolick
- Center for Global Health Equity, Division of Infectious Diseases and International Health, University of Virginia School of Medicine, Charlottesville, Virginia 22908, United States
| | - Richard L. Guerrant
- Center for Global Health Equity, Division of Infectious Diseases and International Health, University of Virginia School of Medicine, Charlottesville, Virginia 22908, United States
| | - Parastoo Azadi
- Complex Carbohydrate Research Center, University of Georgia, 315 Riverbend Road, Athens, Georgia 30602, United States
| | - Kenneth K. S. Ng
- Department of Chemistry and Biochemistry, University of Windsor, 401 Sunset Avenue, Windsor, Ontario N9B 3P4, Canada
| | - Christine M. Szymanski
- Department of Medical Microbiology and Immunology, University of Alberta, Katz Group Centre, Edmonton, Alberta T6G 2E9, Canada
- Department of Microbiology, University of Georgia, 527 Biological Sciences Building, Athens, Georgia 30602, United States
- Complex Carbohydrate Research Center, University of Georgia, 315 Riverbend Road, Athens, Georgia 30602, United States
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42
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McGuire MK, McGuire MA. Microbiomes and Childhood Malnutrition: What Is the Evidence? ANNALS OF NUTRITION & METABOLISM 2021; 77:1-13. [PMID: 34515050 DOI: 10.1159/000519001] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/04/2021] [Accepted: 08/11/2021] [Indexed: 11/19/2022]
Abstract
Both undernutrition and overnutrition continue to represent enduring global health crises, and with the growing implications of both forms of malnutrition occurring simultaneously in individuals and populations (referred to as the double burden of malnutrition), understanding their biological and environmental causes is a primary research and humanitarian necessity. There is growing evidence of a bidirectional association between variation in the gastrointestinal (GI) microbiome and risk of/resilience to malnutrition during early life. For example, studies of siblings who discordantly do or do not develop severe malnutrition show clear differences in the diversity and composition of fecal microbiomes. These differences are transiently lessened during refeeding but re-emerge thereafter. These findings have been somewhat recapitulated using animal models, but small sample sizes and limited range complicate interpretation of results and applicability to humans. Mechanisms driving these differences are currently unknown but likely involve a combination of inflammatory pathways (and perhaps antioxidant status of the host) and effects on nutrient availability, requirements, and utilization by both host and microbe. A less robust literature also suggests that variation in GI microbiome is associated with risk for obesity during childhood. The putative impact of GI microbiomes on malnutrition is likely modified by a variety of important variables such as genetics (likely driven, in part, by evolution), environmental pathogen exposure and its timing, dietary factors, and cultural/societal pattern (e.g., use of antibiotics). Given the growing double burden of malnutrition, this topic demands a focused interdisciplinary approach that expands from merely characterizing differences and longitudinal changes in fecal microbes to examining their functionality during early life. Understanding the complex composition of human milk and how its components impact establishment and maintenance of the recipient infant's GI microbiome will also undoubtedly shed important light on this topic.
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Affiliation(s)
- Michelle K McGuire
- Margaret Ritchie School of Family and Consumer Sciences, University of Idaho, Moscow, Idaho, USA
| | - Mark A McGuire
- Department of Animal, Veterinary, and Food Sciences, University of Idaho, Moscow, Idaho, USA
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43
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Iddrisu I, Monteagudo-Mera A, Poveda C, Pyle S, Shahzad M, Andrews S, Walton GE. Malnutrition and Gut Microbiota in Children. Nutrients 2021; 13:nu13082727. [PMID: 34444887 PMCID: PMC8401185 DOI: 10.3390/nu13082727] [Citation(s) in RCA: 71] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Revised: 07/26/2021] [Accepted: 08/04/2021] [Indexed: 12/13/2022] Open
Abstract
Malnutrition continues to threaten the lives of millions across the world, with children being hardest hit. Although inadequate access to food and infectious disease are the primary causes of childhood malnutrition, the gut microbiota may also contribute. This review considers the evidence on the role of diet in modifying the gut microbiota, and how the microbiota impacts childhood malnutrition. It is widely understood that the gut microbiota of children is influenced by diet, which, in turn, can impact child nutritional status. Additionally, diarrhoea, a major contributor to malnutrition, is induced by pathogenic elements of the gut microbiota. Diarrhoea leads to malabsorption of essential nutrients and reduced energy availability resulting in weight loss, which can lead to malnutrition. Alterations in gut microbiota of severe acute malnourished (SAM) children include increased Proteobacteria and decreased Bacteroides levels. Additionally, the gut microbiota of SAM children exhibits lower relative diversity compared with healthy children. Thus, the data indicate a link between gut microbiota and malnutrition in children, suggesting that treatment of childhood malnutrition should include measures that support a healthy gut microbiota. This could be of particular relevance in sub-Saharan Africa and Asia where prevalence of malnutrition remains a major threat to the lives of millions.
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Affiliation(s)
- Ishawu Iddrisu
- Department of Food and Nutritional Sciences, University of Reading, Whiteknights, Reading RG6 6AX, UK; (I.I.); (A.M.-M.); (C.P.)
| | - Andrea Monteagudo-Mera
- Department of Food and Nutritional Sciences, University of Reading, Whiteknights, Reading RG6 6AX, UK; (I.I.); (A.M.-M.); (C.P.)
| | - Carlos Poveda
- Department of Food and Nutritional Sciences, University of Reading, Whiteknights, Reading RG6 6AX, UK; (I.I.); (A.M.-M.); (C.P.)
| | - Simone Pyle
- Unilever R&D, Colworth Park, Sharnbrook, Bedfordshire MK44 1LQ, UK;
| | - Muhammad Shahzad
- Institute of Basic Medical Sciences, Khyber Medical University, Peshawar 25100, Pakistan;
| | - Simon Andrews
- School of Biological Sciences, University of Reading, Whiteknights, Reading RG6 6AX, UK;
| | - Gemma Emily Walton
- Department of Food and Nutritional Sciences, University of Reading, Whiteknights, Reading RG6 6AX, UK; (I.I.); (A.M.-M.); (C.P.)
- Correspondence:
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44
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Mehta S, Huey SL, McDonald D, Knight R, Finkelstein JL. Nutritional Interventions and the Gut Microbiome in Children. Annu Rev Nutr 2021; 41:479-510. [PMID: 34283919 DOI: 10.1146/annurev-nutr-021020-025755] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
The gut microbiome plays an integral role in health and disease, and diet is a major driver of its composition, diversity, and functional capacity. Given the dynamic development of the gut microbiome in infants and children, it is critical to address two major questions: (a) Can diet modify the composition, diversity, or function of the gut microbiome, and (b) will such modification affect functional/clinical outcomes including immune function, cognitive development, and overall health? We synthesize the evidence on the effect of nutritional interventions on the gut microbiome in infants and children across 26 studies. Findings indicate the need to study older children, assess the whole intestinal tract, and harmonize methods and interpretation of findings, which are critical for informing meaningful clinical and public health practice. These findings are relevant for precision health, may help identify windows of opportunity for intervention, and may inform the design and delivery of such interventions. Expected final online publication date for the Annual Review of Nutrition, Volume 41 is September 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
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Affiliation(s)
- Saurabh Mehta
- Institute for Nutritional Sciences, Global Health, and Technology, Cornell University, Ithaca, New York 14853, USA; .,Division of Nutritional Sciences, Cornell University, Ithaca, New York 14853, USA
| | - Samantha L Huey
- Division of Nutritional Sciences, Cornell University, Ithaca, New York 14853, USA
| | - Daniel McDonald
- Center for Microbiome Innovation and Department of Pediatrics, University of California San Diego, La Jolla, California 92093, USA
| | - Rob Knight
- Center for Microbiome Innovation and Department of Pediatrics, University of California San Diego, La Jolla, California 92093, USA.,Departments of Bioengineering and Computer Science & Engineering, University of California San Diego, La Jolla, California 92093, USA
| | - Julia L Finkelstein
- Institute for Nutritional Sciences, Global Health, and Technology, Cornell University, Ithaca, New York 14853, USA; .,Division of Nutritional Sciences, Cornell University, Ithaca, New York 14853, USA
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45
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Amato KR, Arrieta MC, Azad MB, Bailey MT, Broussard JL, Bruggeling CE, Claud EC, Costello EK, Davenport ER, Dutilh BE, Swain Ewald HA, Ewald P, Hanlon EC, Julion W, Keshavarzian A, Maurice CF, Miller GE, Preidis GA, Segurel L, Singer B, Subramanian S, Zhao L, Kuzawa CW. The human gut microbiome and health inequities. Proc Natl Acad Sci U S A 2021; 118:e2017947118. [PMID: 34161260 PMCID: PMC8237592 DOI: 10.1073/pnas.2017947118] [Citation(s) in RCA: 97] [Impact Index Per Article: 24.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Individuals who are minoritized as a result of race, sexual identity, gender, or socioeconomic status experience a higher prevalence of many diseases. Understanding the biological processes that cause and maintain these socially driven health inequities is essential for addressing them. The gut microbiome is strongly shaped by host environments and affects host metabolic, immune, and neuroendocrine functions, making it an important pathway by which differences in experiences caused by social, political, and economic forces could contribute to health inequities. Nevertheless, few studies have directly integrated the gut microbiome into investigations of health inequities. Here, we argue that accounting for host-gut microbe interactions will improve understanding and management of health inequities, and that health policy must begin to consider the microbiome as an important pathway linking environments to population health.
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Affiliation(s)
- Katherine R Amato
- Department of Anthropology, Northwestern University, Evanston, IL 60208;
| | - Marie-Claire Arrieta
- Department of Physiology and Pharmacology, University of Calgary, Calgary, AB T2N 4N1, Canada
- Department of Pediatrics, University of Calgary, Calgary, AB T2N 4N1, Canada
| | - Meghan B Azad
- Children's Hospital Research Institute of Manitoba, Winnipeg, MB R3E 3P4, Canada
- Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, MB R3A 1S1, Canada
| | - Michael T Bailey
- Center for Microbial Pathogenesis, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH 43205
- Department of Pediatrics, The Ohio State University, Columbus, OH 43210
| | - Josiane L Broussard
- Department of Health and Exercise Science, Colorado State University, Fort Collins, CO 80521
| | - Carlijn E Bruggeling
- Department of Pathology, Radboud University Medical Centre, 6500 HB Nijmegen, The Netherlands
| | - Erika C Claud
- Department of Pediatrics, The University of Chicago, Chicago, IL 60637
| | - Elizabeth K Costello
- Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305
| | - Emily R Davenport
- Department of Biology, Huck Institutes of the Life Sciences, Institute for Computational and Data Sciences, Pennsylvania State University, University Park, PA 16802
| | - Bas E Dutilh
- Theoretical Biology and Bioinformatics, Science for Life, Utrecht University, 3584 CH Utrecht, The Netherlands
- Centre for Molecular and Biomolecular Informatics, Radboud University Medical Centre, 6525 GA Nijmegen, The Netherlands
| | | | - Paul Ewald
- Department of Biology, University of Louisville, Louisville, KY 40292
| | - Erin C Hanlon
- Department of Medicine, Section of Endocrinology, Diabetes and Metabolism, University of Chicago, Chicago, IL 60637
| | | | - Ali Keshavarzian
- Rush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, IL 60612
| | - Corinne F Maurice
- Microbiology and Immunology Department, McGill University, Montreal, QC H3A 2B4, Canada
| | - Gregory E Miller
- Department of Psychology, Northwestern University, Evanston, IL 60208
- Institute for Policy Research, Northwestern University, Evanston, IL 60208
| | - Geoffrey A Preidis
- Section of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, TX 77030
| | - Laure Segurel
- Eco-anthropologie, Muséum National d'Histoire Naturelle-CNRS-Université de Paris, 75016 Paris, France
| | - Burton Singer
- Emerging Pathogens Institute, University of Florida, Gainesville, FL 32608
| | - Sathish Subramanian
- Department of Medicine, Division of Gastroenterology, Massachusetts General Hospital, Boston, MA 02114
- Broad Institute of MIT and Harvard, Cambridge, MA 02142
| | - Liping Zhao
- State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China
- Department of Biochemistry and Microbiology, School of Environmental and Biological Sciences, Rutgers New Jersey Institute for Food, Nutrition, and Health, Rutgers University-New Brunswick, New Brunswick, NJ 08901
| | - Christopher W Kuzawa
- Department of Anthropology, Northwestern University, Evanston, IL 60208
- Institute for Policy Research, Northwestern University, Evanston, IL 60208
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Shivakumar N, Sivadas A, Devi S, Jahoor F, McLaughlin J, Smith CP, Kurpad AV, Mukhopadhyay A. Gut microbiota profiles of young South Indian children: Child sex-specific relations with growth. PLoS One 2021; 16:e0251803. [PMID: 33989353 PMCID: PMC8121364 DOI: 10.1371/journal.pone.0251803] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Accepted: 05/04/2021] [Indexed: 12/21/2022] Open
Abstract
Gut microbiota has been implicated as a modifier of childhood growth. Here, 16S rRNA sequencing-based fecal microbiota profiles of 18–24 month old Indian children were evaluated (n = 41), in relation to their anthropometric parameters, intestinal permeability, body composition and total energy expenditure. Pathway analyses were conducted to assess microbial functions related to stunting, underweight and wasting. The fecal microbiota was enriched in Prevotella 9, Bifidobacterium and Escherichia-Shigella. Weight, weight-for-age Z-scores (WAZ) and weight-for-length Z-scores (WLZ), along with age, acted as covariates of microbiota variation specifically in boys (n = 23). Bifidobacterium longum subsp longum abundance was positively associated with WAZ while Bifidobacterium bifidum and Bifidobacterium breve abundances were negatively associated with age. The lipopolysaccharide biosynthesis pathway was upregulated in stunted (n = 16) and wasted (n = 8) children. Findings from this study indicate that child sex may be a critical modifier of the role of gut microbiota on childhood growth.
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Affiliation(s)
- Nirupama Shivakumar
- Division of Nutrition, St. John’s Research Institute, St. John’s National Academy of Health Sciences, Bangalore, India
| | - Ambily Sivadas
- Division of Nutrition, St. John’s Research Institute, St. John’s National Academy of Health Sciences, Bangalore, India
| | - Sarita Devi
- Division of Nutrition, St. John’s Research Institute, St. John’s National Academy of Health Sciences, Bangalore, India
| | - Farook Jahoor
- Department of Pediatrics, USDA/Agricultural Research Service Children’s Nutrition Research Center, Baylor College of Medicine, Houston, Texas, United States of America
| | - John McLaughlin
- Faculty of Biology, Division of Diabetes, Endocrinology and Gastroenterology, School of Medical Sciences, Medicine & Health, Manchester Academic Health Sciences Centre, University of Manchester, Clinical Sciences Building, Salford Royal Hospital, Salford, United Kingdom
| | - Craig P. Smith
- Faculty of Biology, Division of Diabetes, Endocrinology and Gastroenterology, School of Medical Sciences, Medicine & Health, Manchester Academic Health Sciences Centre, University of Manchester, Clinical Sciences Building, Salford Royal Hospital, Salford, United Kingdom
| | - Anura V. Kurpad
- Division of Nutrition, St. John’s Research Institute, St. John’s National Academy of Health Sciences, Bangalore, India
- Department of Physiology, St. John’s Medical College, St. John’s National Academy of Health Sciences, Bangalore, India
| | - Arpita Mukhopadhyay
- Division of Nutrition, St. John’s Research Institute, St. John’s National Academy of Health Sciences, Bangalore, India
- * E-mail:
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47
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Gut bacterial profile in Indian children of varying nutritional status: a comparative pilot study. Eur J Nutr 2021; 60:3971-3985. [PMID: 33929588 PMCID: PMC8085102 DOI: 10.1007/s00394-021-02571-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Accepted: 04/19/2021] [Indexed: 12/15/2022]
Abstract
PURPOSE Childhood malnutrition is a multifactorial disease, responsible for nearly half of all deaths in children under five. Lately, the probable association of a dysbiotic gut to malnutrition is also being eagerly investigated. The current study is an attempt to investigate this purported association through assessing the abundance of major gut bacterial phyla (Firmicutes, Bacteroidetes, Actinobacteria and Proteobacteria), probionts (Bifidobacteria and Lactobacillus), butyrogens (Faecalibacterium and Roseburia) and pathogens (Escherichia and Klebsiella). METHODS The study was conducted in the suburbs of Chandigarh, India in the year 2017. The children enrolled in the study were part of Anganwadis (Rural Child Care Centres) set up under Integrated Child Development Scheme (ICDS) of Government of India where community-based management approach is being widely used for treatment of malnutrition. We used qPCR based absolute quantification as well as the 16S rRNA amplicon sequencing approach for our study. The study population included 30 children in the age group of 2-5 years who were categorized into three groups Healthy, Moderate Acute Malnutrition (MAM) and Severe Acute Malnutrition (SAM), with 10 children in each group. The selection of participants was made based on Z scores. Further, statistical tools like the One-way ANOVA, PCA and PLSDA were employed to analyze and compare the gut bacterial profile. RESULTS Our investigation through the qPCR (Absolute quantification) approach revealed a significantly higher abundance of Actinobacteria in healthy, in comparison to children suffering from Severe Acute Malnutrition (SAM). Consequently, the same trend was also reflected with respect to Bifidobacterium, a prominent member of the Actinobacteria phylum. Conversely, a significant higher abundance of Lactobacillus with the diminishing nutritional status was recorded. Escherichia showed a significant higher abundance in healthy subjects compared to the malnourished; however, no such difference in abundance of Klebsiella was observed. The other target phyla [Bacteroidetes, Firmicutes and Proteobacteria] and genera (Faecalibacterium and Roseburia) showed differences in abundance; however, these were non-significant. Similarly, the bacterial taxonomy analysis of 16S rRNA gene amplicon sequencing data revealed the higher abundance of phylum Actinobacteria and its member Bifidobacterium with lower prevalence of Lactobacillus in healthy children. CONCLUSION The pattern of gut microbiota profile in malnourished subjects suggests a dysbiotic gut depleted in Bifidobacteria, a core member of the consortia of beneficial anaerobes of the healthy child gut.
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48
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Mehta O, Inbaraj LR, Astbury S, Grove JI, Norman G, Aithal GP, Valdes AM, Vijay A. Gut Microbial Profile Is Associated With Residential Settings and Not Nutritional Status in Adults in Karnataka, India. Front Nutr 2021; 8:595756. [PMID: 33708787 PMCID: PMC7940358 DOI: 10.3389/fnut.2021.595756] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2020] [Accepted: 01/25/2021] [Indexed: 12/12/2022] Open
Abstract
Undernutrition is a leading contributor to disease and disability in people of all ages. Several studies have reported significant association between nutritional status and gut microbiome composition but other factors such as demographic settings may also influence the adult microbiome. The relationship between undernourishment and gut microbiome in adults has not been described to date. In this study, we compared the gut microbiome in fecal samples of 48 individuals, from two demographic settings (rural and urban slum) in Karnataka, India using 16S rRNA sequencing. Nutritional status was assessed based on BMI, with a BMI of < 18.5 kg/m2 classified as undernourished, and a BMI in the range 18.5-25 kg/m2 as nourished. We analyzed 25 individuals from rural settings (12 undernourished and 13 nourished) and 23 individuals from urban slum settings (11 undernourished and 12 nourished). We found no significant difference in overall gut microbial diversity (Shannon and Unweighted UniFrac) between undernourished and nourished individuals in either geographical settings, however, microbial taxa at the phylum level (i.e., Firmicutes and Proteobacteria) and beta diversity (unweighted UniFrac) differed significantly between the rural and urban slum settings. By predicting microbial function from 16S data profiling we found significant differences in metabolic pathways present in the gut microbiota from people residing in different settings; specifically, those related to carbohydrate and lipid metabolism. The weighted sum of the KEGG Orthologs associated with carbohydrate metabolism (Spearman's correlation coefficient, ρ = -0.707, p < 0.001), lipid metabolism (Spearman's correlation coefficient, ρ = -0.330, p < 0.022) and biosynthesis of secondary metabolites (Spearman's correlation coefficient, ρ = -0.507, p < 0.001) were decreased in the urban slum group compared to the rural group. In conclusion, we report that the geographical location of residence is associated with differences in gut microbiome composition in adults. We found no significant differences in microbiome composition between nourished and undernourished adults from urban slum or rural settings in India.
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Affiliation(s)
- Ojasvi Mehta
- Nottingham Digestive Diseases Center, School of Medicine, University of Nottingham, Nottingham, United Kingdom
- National Institute of Health Research (NIHR) Nottingham Biomedical Research Center, Nottingham University Hospitals National Health Service (NHS) Trust and University of Nottingham, Nottingham, United Kingdom
| | | | - Stuart Astbury
- Nottingham Digestive Diseases Center, School of Medicine, University of Nottingham, Nottingham, United Kingdom
- National Institute of Health Research (NIHR) Nottingham Biomedical Research Center, Nottingham University Hospitals National Health Service (NHS) Trust and University of Nottingham, Nottingham, United Kingdom
| | - Jane I. Grove
- Nottingham Digestive Diseases Center, School of Medicine, University of Nottingham, Nottingham, United Kingdom
- National Institute of Health Research (NIHR) Nottingham Biomedical Research Center, Nottingham University Hospitals National Health Service (NHS) Trust and University of Nottingham, Nottingham, United Kingdom
| | - Gift Norman
- Department of Community Health, Bangalore Baptist Hospital, Bangalore, India
| | - Guruprasad P. Aithal
- Nottingham Digestive Diseases Center, School of Medicine, University of Nottingham, Nottingham, United Kingdom
- National Institute of Health Research (NIHR) Nottingham Biomedical Research Center, Nottingham University Hospitals National Health Service (NHS) Trust and University of Nottingham, Nottingham, United Kingdom
| | - Ana M. Valdes
- National Institute of Health Research (NIHR) Nottingham Biomedical Research Center, Nottingham University Hospitals National Health Service (NHS) Trust and University of Nottingham, Nottingham, United Kingdom
- Division of Rheumatology, Orthopedics and Dermatology, School of Medicine, University of Nottingham, Nottingham, United Kingdom
| | - Amrita Vijay
- Nottingham Digestive Diseases Center, School of Medicine, University of Nottingham, Nottingham, United Kingdom
- National Institute of Health Research (NIHR) Nottingham Biomedical Research Center, Nottingham University Hospitals National Health Service (NHS) Trust and University of Nottingham, Nottingham, United Kingdom
- Division of Rheumatology, Orthopedics and Dermatology, School of Medicine, University of Nottingham, Nottingham, United Kingdom
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49
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Kumbhare SV, Patangia DV, Mongad DS, Bora A, Bavdekar AR, Shouche YS. Gut microbial diversity during pregnancy and early infancy: an exploratory study in the Indian population. FEMS Microbiol Lett 2021; 367:5735435. [PMID: 32053163 DOI: 10.1093/femsle/fnaa022] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2019] [Accepted: 02/11/2020] [Indexed: 12/13/2022] Open
Abstract
The gut microbial community is known to influence the human health and disease state and is shaped by various factors since birth. It is now evident that understanding the alterations in these commensal microbes during crucial stages of life is of utmost importance to determine and predict the health status of an individual. To study the gut microbiota in two such vital stages, pregnancy and infancy, we analyzed gut microbial communities from 20 mother-infant dyads at different stages of pregnancy and early infancy. In total, we analyzed 80 fecal samples for profiling the gut microbial community using 16S rRNA gene-based sequencing. We observed no significant alterations in the gut bacterial diversity during pregnancy; however, significant alterations were observed during the period from birth to six months in infants, with a reduction in Staphylococcus and Enterococcus and an increase in Bifidobacterium and Streptococcus with a more stable microbial community at the age of six months.
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Affiliation(s)
- Shreyas V Kumbhare
- National Centre for Cell Science, Savitribai Phule University of Pune Campus, Ganeshkhind, Pune, Maharashtra, India, 411007
| | - Dhrati V Patangia
- National Centre for Cell Science, Savitribai Phule University of Pune Campus, Ganeshkhind, Pune, Maharashtra, India, 411007
| | - Dattatray S Mongad
- National Centre for Cell Science, Savitribai Phule University of Pune Campus, Ganeshkhind, Pune, Maharashtra, India, 411007
| | - Abhijeet Bora
- King Edward Memorial Hospital Research Centre, Pune, Maharashtra, India, 411011
| | - Ashish R Bavdekar
- King Edward Memorial Hospital Research Centre, Pune, Maharashtra, India, 411011
| | - Yogesh S Shouche
- National Centre for Cell Science, Savitribai Phule University of Pune Campus, Ganeshkhind, Pune, Maharashtra, India, 411007
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Gut microbiota profile of Indonesian stunted children and children with normal nutritional status. PLoS One 2021; 16:e0245399. [PMID: 33497390 PMCID: PMC7837488 DOI: 10.1371/journal.pone.0245399] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2020] [Accepted: 12/29/2020] [Indexed: 01/03/2023] Open
Abstract
The gut microbiota has been shown to play a role in energy metabolism of the host. Dysbiosis of the gut microbiota may predispose to obesity on the one hand, and stunting on the other. The aim of the study was to study the difference in gut microbiota composition of stunted Indonesian children and children of normal nutritional status between 3 and 5 years. Fecal samples and anthropometric measurements, in addition to economic and hygiene status were collected from 78 stunted children and 53 children with normal nutritional status in two regions in Banten and West Java provinces: Pandeglang and Sumedang, respectively. The gut microbiota composition was determined by sequencing amplicons of the V3-V4 region of the 16S rRNA gene. The composition was correlated to nutritional status and anthropometric parameters. Macronutrient intake was on average lower in stunted children, while energy-loss in the form of short-chain fatty acids (SCFA) and branched-chain fatty acids (BCFA) appeared to be higher in stunted children. In stunted children, at the phylum level the relative abundance of Bacteroidetes (44.4%) was significantly lower than in normal children (51.3%; p-value 2.55*10-4), while Firmicutes was significantly higher (45.7% vs. 39.8%; p-value 5.89*10-4). At the genus level, overall Prevotella 9 was the most abundant genus (average of 27%), and it was significantly lower in stunted children than in normal children (23.5% vs. 30.5%, respectively; q-value 0.059). Thirteen other genera were significantly different between stunted and normal children (q-value < 0.1), some of which were at low relative abundance and present in only a few children. Prevotella 9 positively correlated with height (in line with its higher relative abundance in normal children) and weight. In conclusion, Prevotella 9, which was the most abundant genus in the children, was significantly lower in stunted children. The abundance of Prevotella has been correlated with dietary fibre intake, which was lower in these stunted children. Since fibres are fermented by the gut microbiota into SCFA, and these SCFA are a source of energy for the host, increasing the proportion of Prevotella in stunted children may be of benefit. Whether this would prevent the occurrence of stunting or even has the potential to revert it, remains to be seen in follow up research.
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