The infant gut microbiome and cognitive development in malnutrition.

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.

Bioactive glycans in a microbiome-directed food for children with malnutrition.

Evidence is accumulating that perturbed postnatal development of the gut microbiome contributes to childhood malnutrition1-4. Here we analyse biospecimens from a randomized, controlled trial of a microbiome-directed complementary food (MDCF-2) that produced superior rates of weight gain compared with a calorically more dense conventional ready-to-use supplementary food in 12-18-month-old Bangladeshi children with moderate acute malnutrition4. We reconstructed 1,000 bacterial genomes (metagenome-assembled genomes (MAGs)) from the faecal microbiomes of trial participants, identified 75 MAGs of which the abundances were positively associated with ponderal growth (change in weight-for-length Z score (WLZ)), characterized changes in MAG gene expression as a function of treatment type and WLZ response, and quantified carbohydrate structures in MDCF-2 and faeces. The results reveal that two Prevotella copri MAGs that are positively associated with WLZ are the principal contributors to MDCF-2-induced expression of metabolic pathways involved in utilizing the component glycans of MDCF-2. The predicted specificities of carbohydrate-active enzymes expressed by their polysaccharide-utilization loci are correlated with (1) the in vitro growth of Bangladeshi P. copri strains, possessing varying degrees of polysaccharide-utilization loci and genomic conservation with these MAGs, in defined medium containing different purified glycans representative of those in MDCF-2, and (2) the levels of faecal carbohydrate structures in the trial participants. These associations suggest that identifying bioactive glycan structures in MDCFs metabolized by growth-associated bacterial taxa will help to guide recommendations about their use in children with acute malnutrition and enable the development of additional formulations.

Gut microbiota in regulation of childhood bone growth.

Childhood stunting and wasting, or decreased linear and ponderal growth associated with undernutrition, continue to be a major global public health challenge. Although many of the current therapeutic and dietary interventions have significantly reduced childhood mortality caused by undernutrition, there remain great inefficacies in improving childhood stunting. Longitudinal bone growth in children is governed by different genetic, nutritional and other environmental factors acting systemically on the endocrine system and locally at the growth plate. Recent studies have shown that this intricate interplay between nutritional and hormonal regulation of the growth plate could involve the gut microbiota, highlighting the importance of a holistic approach in tackling childhood undernutrition. In this review, I focus on the mechanistic insights provided by these recent advances in gut microbiota research and discuss ongoing development of microbiota-based therapeutics in humans, which could be the missing link in solving undernutrition and childhood stunting.

Growing up: A NOD2 our microbes.

In a recent report in Science, Schwarzer and colleagues demonstrate the growth benefits of treatment with Lactiplantibacillus plantarum strain WJL in a preclinical mouse model of chronic undernutrition. L. plantarum influences the somatotropic axis to promote growth through intestinal epithelial NOD2 sensing.

Prophylactic Treatment of Undernourished Mice with Cotrimoxazole Induces a Different Profile of Dysbiosis with Functional Metabolic Alterations.

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.

Cross-feeding between intestinal pathobionts promotes their overgrowth during undernutrition.

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.

Re-examining chemically defined liquid diets through the lens of the microbiome.

Trends in nutritional science are rapidly shifting as information regarding the value of eating unprocessed foods and its salutary effect on the human microbiome emerge. Unravelling the evolution and ecology by which humans have harboured a microbiome that participates in every facet of health and disease is daunting. Most strikingly, the host habitat has sought out naturally occurring foodstuff that can fulfil its own metabolic needs and also the needs of its microbiota, each of which remain inexorably connected to one another. With the introduction of modern medicine and complexities of critical care, came the assumption that the best way to feed a critically ill patient is by delivering fibre-free chemically defined sterile liquid foods (that is, total enteral nutrition). In this Perspective, we uncover the potential flaws in this assumption and discuss how emerging technology in microbiome sciences might inform the best method of feeding malnourished and critically ill patients.

Immune response and gut microbiota of mice on a diet mimicking eating habits of elderly with risk of malnutrition development.

The number of elderlies is increasing but prevalence of malnutrition has been reported. The aim of the study was to determine the significance of short-term nutritional deficiencies in mice. Immune status was assessed through flow cytometry of leucocytes in Peyer's patches (PP) and mesenteric lymph nodes (MLN), and intestinal microbiota was evaluated by terminal restriction fragment length polymorphism (T-RFLP). C57BL/6NCrl mice fed standard diet (StD) or experimental diet high in fat, and low in carbohydrates, protein, fibre, vitamins, and minerals (ExpD) for 2 or 4 weeks. ExpD-animals gained less weight, increased liver lipids, and developed splenomegaly. Diet affected regulatory T-cells, gut homing receptors and TLR2 and TLR4 in PP and MLN and the microbiota was influenced. Partial least squares models on flow cytometry- and T-RFLP data demonstrated correlations between microbial communities and immune phenotyping. Our model shows similarities to malnourished elderly and interactions between intestinal bacteria and the immune system.

Millet-based supplement restored gut microbial diversity of acute malnourished pigs.

The tight association between malnutrition and gut microbiota (GM) dysbiosis enables microbiota-targeting intervention to be a promising strategy. Thus, we used a malnourished pig model to investigate the host response and GM alterations under different diet supplementation strategies. Pigs at age of 4 weeks were fed with pure maize diet to induce malnutrition symptoms, and followed by continuous feeding with maize (Maize, n = 8) or re-feeding using either corn-soy-blend (CSB+, n = 10) or millet-soy-blend based (MSB+, n = 10) supplementary food for 3 weeks. Meanwhile, 8 pigs were fed on a standard formulated ration as control (Ref). The effect of nutritional supplementation was assessed by the growth status, blood chemistry, gastrointestinal pathology, mucosal microbiota composition and colon production of short-chain fatty acids. Compared with purely maize-fed pigs, both CSB+ and MSB+ elevated the concentrations of total protein and globulin in blood. These pigs still showed most malnutrition symptoms after the food intervention period. MSB+ had superior influence on the GM development, exhibiting better performance in both structural and functional aspects. MSB+ pigs were colonized by less Proteobacteria but more Bacteroidetes, Firmicutes and Lachnospira spp. Pearson's correlation analysis indicated a strong correlation between the abundance of mucosal e.g., Faecalibacterium and Lachnospira spp. and body weight, crown-rump length and total serum protein. In conclusion, the malnutrition symptoms were accompanied by an aberrant GM, and millet-based nutritional supplementation showed promising potentials to restore the reduced GM diversity implicated in pig malnutrition.

A Microbiota-Directed Food Intervention for Undernourished Children.

BACKGROUND: More than 30 million children worldwide have moderate acute malnutrition. Current treatments have limited effectiveness, and much remains unknown about the pathogenesis of this condition. Children with moderate acute malnutrition have perturbed development of their gut microbiota. METHODS: In this study, we provided a microbiota-directed complementary food prototype (MDCF-2) or a ready-to-use supplementary food (RUSF) to 123 slum-dwelling Bangladeshi children with moderate acute malnutrition between the ages of 12 months and 18 months. The supplementation was given twice daily for 3 months, followed by 1 month of monitoring. We obtained weight-for-length, weight-for-age, and length-for-age z scores and mid-upper-arm circumference values at baseline and every 2 weeks during the intervention period and at 4 months. We compared the rate of change of these related phenotypes between baseline and 3 months and between baseline and 4 months. We also measured levels of 4977 proteins in plasma and 209 bacterial taxa in fecal samples. RESULTS: A total of 118 children (59 in each study group) completed the intervention. The rates of change in the weight-for-length and weight-for-age z scores are consistent with a benefit of MDCF-2 on growth over the course of the study, including the 1-month follow-up. Receipt of MDCF-2 was linked to the magnitude of change in levels of 70 plasma proteins and of 21 associated bacterial taxa that were positively correlated with the weight-for-length z score (P<0.001 for comparisons of both protein and bacterial taxa). These proteins included mediators of bone growth and neurodevelopment. CONCLUSIONS: These findings provide support for MDCF-2 as a dietary supplement for young children with moderate acute malnutrition and provide insight into mechanisms by which this targeted manipulation of microbiota components may be linked to growth. (Supported by the Bill and Melinda Gates Foundation and the National Institutes of Health; ClinicalTrials.gov number, NCT04015999.).

Effects of probiotics on gastrointestinal complications and nutritional status of postoperative patients with esophageal cancer: A protocol of randomized controlled trial.

BACKGROUND: Gastrointestinal complications and malnutrition are common problems that affect postoperative rehabilitation and survival of patients with esophageal cancer. Evidence has shown that probiotics have a positive effect on improving gastrointestinal complications and nutritional status of patients with esophageal cancer after surgery, but there is a lack of prospective studies on this topic. We designed this prospective randomized controlled trial to evaluate the effects of probiotics on gastrointestinal complications and nutritional status in patients with postoperative esophageal cancer. METHODS: This is a prospective, randomized, double-blind, placebo-controlled trial. It was approved by the Clinical Research Ethics Committee of our hospital. 192 patients will be randomly divided into probiotics group and the placebo group in a 1:1 ratio. After operation, probiotics and placebo will be given orally for 8 weeks. The indexes of nutritional status and incidence of digestive tract complications will be recorded and the data will be analyzed by SPSS 18.0 software. DISCUSSION: This study will evaluate the effect of probiotics on gastrointestinal complications and nutritional status of postoperative patients with esophageal cancer. The results of this study will provide clinical basis for the use of probiotics in postoperative treatment of esophageal cancer. TRIAL REGISTRATION: OSF Registration number: D DOI 10.17605/OSF.IO/QHW86.

Priming for Life: Early Life Nutrition and the Microbiota-Gut-Brain Axis.

Microbes colonize the human body during the first moments of life and coexist with the host throughout the lifespan. Intestinal microbiota and their metabolites aid in the programming of important bodily systems such as the immune and the central nervous system during critical temporal windows of development, with possible structural and functional implications throughout the lifespan. These critical developmental windows perinatally (during the first 1000 days) are susceptible timepoints for insults that can endure long lasting effects on the microbiota-gut-brain axis. Environmental and parental factors like host genetics, mental health, nutrition, delivery and feeding mode, exposure to antibiotics, immune activation and microbiota composition antenatally, are all factors that are able to modulate the microbiota composition of mother and infant and may thus regulate important bodily functions. Among all these factors, early life nutrition plays a pivotal role in perinatal programming and in the modulation of offspring microbiota from birth throughout lifespan. This review aims to present current data on the impact of early life nutrition and microbiota priming of important bodily systems and all the factors influencing the microbial coexistence with the host during early life development.

Escherichia coli Nissle 1917 administered as a dextranomar microsphere biofilm enhances immune responses against human rotavirus in a neonatal malnourished pig model colonized with human infant fecal microbiota.

Human rotavirus (HRV) is a leading cause of diarrhea in children. It causes significant morbidity and mortality, especially in low- and middle-income countries (LMICs), where HRV vaccine efficacy is low. The probiotic Escherichia coli Nissle (EcN) 1917 has been widely used in the treatment of enteric diseases in humans. However, repeated doses of EcN are required to achieve maximum beneficial effects. Administration of EcN on a microsphere biofilm could increase probiotic stability and persistence, thus maximizing health benefits without repeated administrations. Our aim was to investigate immune enhancement by the probiotic EcN adhered to a dextranomar microsphere biofilm (EcN biofilm) in a neonatal, malnourished piglet model transplanted with human infant fecal microbiota (HIFM) and infected with rotavirus. To create malnourishment, pigs were fed a reduced amount of bovine milk. Decreased HRV fecal shedding and protection from diarrhea were evident in the EcN biofilm treated piglets compared with EcN suspension and control groups. Moreover, EcN biofilm treatment enhanced natural killer cell activity in blood mononuclear cells (MNCs). Increased frequencies of activated plasmacytoid dendritic cells (pDC) in systemic and intestinal tissues and activated conventional dendritic cells (cDC) in blood and duodenum were also observed in EcN biofilm as compared with EcN suspension treated pigs. Furthermore, EcN biofilm treated pigs had increased frequencies of systemic activated and resting/memory antibody forming B cells and IgA+ B cells in the systemic tissues. Similarly, the mean numbers of systemic and intestinal HRV-specific IgA antibody secreting cells (ASCs), as well as HRV-specific IgA antibody titers in serum and small intestinal contents, were increased in the EcN biofilm treated group. In summary EcN biofilm enhanced innate and B cell immune responses after HRV infection and ameliorated diarrhea following HRV challenge in a malnourished, HIFM pig model.

Diet Alters Micronutrient Pathways in the Gut and Placenta that Regulate Fetal Growth and Development in Pregnant Mice.

Maternal malnutrition and micronutrient deficiencies can alter fetal development. However, the mechanisms underlying these relationships are poorly understood. We used a systems physiology approach to investigate diet-induced effects on maternal gut microbes and folate/inositol transport in the maternal/fetal gut and placenta. Female mice were fed a control diet (CON) diet, undernourished (UN, restricted by 30% of CON intake) or a high-fat diet (HF, 60% kcals fat) during pregnancy to model normal pregnancy, fetal growth restriction or maternal metabolic dysfunction, respectively. At gestational day 18.5, we assessed circulating folate levels by microbiological assay, relative abundance of gut lactobacilli by G3PhyloChip™, and folate/inositol transporters in placenta and maternal/fetal gut by qPCR/immunohistochemistry. UN and HF-fed mothers had lower plasma folate concentrations vs. CON. Relative abundances of three lactobacilli taxa were higher in HF vs. UN and CON. HF-fed mothers had higher gut proton coupled folate transporter (Pcft) and reduced folate carrier 1 (Rfc1), and lower sodium myo-inositol co-transporter 2 (Smit2), mRNA expression vs. UN and CON. HF placentae had increased folate receptor beta (Frß) expression vs. UN. mRNA expression of Pcft, folate receptor alpha (Frα), and Smit2 was higher in gut of HF fetuses vs. UN and CON. Transporter protein expression was not different between groups. Maternal malnutrition alters abundance of select gut microbes and folate/inositol transporters, which may influence maternal micronutrient status and delivery to the fetus, impacting pregnancy/fetal outcomes.

Nutritional Targeting of the Microbiome as Potential Therapy for Malnutrition and Chronic Inflammation.

Homeostatic interactions with the microbiome are central for a healthy human physiology and nutrition is the main driving force shaping the microbiome. In the past decade, a wealth of preclinical studies mainly using gnotobiotic animal models demonstrated that malnutrition and chronic inflammation stress these homeostatic interactions and various microbial species and their metabolites or metabolic activities have been associated with disease. For example, the dysregulation of the bacterial metabolism of dietary tryptophan promotes an inflammatory environment and susceptibility to pathogenic infection. Clinical studies have now begun to evaluate the therapeutic potential of nutritional and probiotic interventions in malnutrition and chronic inflammation to ameliorate disease symptoms or even prevent pathogenesis. Here, we therefore summarize the recent progress in this field and propose to move further towards the nutritional targeting of the microbiome for malnutrition and chronic inflammation.

Disruption of ruminal homeostasis by malnutrition involved in systemic ruminal microbiota-host interactions in a pregnant sheep model.

BACKGROUND: Undernutrition is a prevalent and spontaneous condition in animal production which always affects microbiota-host interaction in gastrointestinal tract. However, how undernutrition affects crosstalk homeostasis is largely unknown. Here, we discover how undernutrition affects microbial profiles and subsequently how microbial metabolism affects the signal transduction and tissue renewal in ruminal epithelium, clarifying the detrimental effect of undernutrition on ruminal homeostasis in a pregnant sheep model. RESULTS: Sixteen pregnant ewes (115 days of gestation) were randomly and equally assigned to the control (CON) and severe feed restriction (SFR) groups. Ewes on SFR treatment were restricted to a 30% level of ad libitum feed intake while the controls were fed normally. After 15 days, all ewes were slaughtered to collect ruminal digesta for 16S rRNA gene and metagenomic sequencing and ruminal epithelium for transcriptome sequencing. Results showed that SFR diminished the levels of ruminal volatile fatty acids and microbial proteins and repressed the length, width, and surface area of ruminal papillae. The 16S rRNA gene analysis indicated that SFR altered the relative abundance of ruminal bacterial community, showing decreased bacteria about saccharide degradation (Saccharofermentans and Ruminococcus) and propionate genesis (Succiniclasticum) but increased butyrate producers (Pseudobutyrivibrio and Papillibacter). Metagenome analysis displayed that genes related to amino acid metabolism, acetate genesis, and succinate-pathway propionate production were downregulated upon SFR, while genes involved in butyrate and methane genesis and acrylate-pathway propionate production were upregulated. Transcriptome and real-time PCR analysis of ruminal epithelium showed that downregulated collagen synthesis upon SFR lowered extracellular matrix-receptor interaction, inactivated JAK3-STAT2 signaling pathway, and inhibited DNA replication and cell cycle. CONCLUSIONS: Generally, undernutrition altered rumen bacterial community and function profile to decrease ruminal energy retention, promoted epithelial glucose and fatty acid catabolism to elevate energy supply, and inhibited the proliferation of ruminal epithelial cells. These findings provide the first insight into the systemic microbiota-host interactions that are involved in disrupting the ruminal homeostasis under a malnutrition pattern. Video Abstract.

Nutrition and the Gut Microbiota in 10- to 18-Month-Old Children Living in Urban Slums of Mumbai, India.

In this cross-sectional study, we describe the composition and diversity of the gut microbiota among undernourished children living in urban slums of Mumbai, India, and determine how nutritional status, including anthropometric measurements, dietary intakes from complementary foods, feeding practices, and micronutrient concentrations, is associated with their gut microbiota. We collected rectal swabs from children aged 10 to 18 months living in urban slums of Mumbai participating in a randomized controlled feeding trial and conducted 16S rRNA sequencing to determine the composition of the gut microbiota. Across the study cohort, Proteobacteria dominated the gut microbiota at over 80% relative abundance, with Actinobacteria representation at <4%, suggesting immaturity of the gut. Increased microbial α-diversity was associated with current breastfeeding, greater head circumference, higher fat intake, and lower hemoglobin concentration and weight-for-length Z-score. In redundancy analyses, 47% of the variation in Faith's phylogenetic diversity (Faith's PD) could be accounted for by age and by iron and polyunsaturated fatty acid intakes. Differences in community structure (ß-diversity) of the microbiota were observed among those consuming fats and oils the previous day compared to those not consuming fats and oils the previous day. Our findings suggest that growth, diet, and feeding practices are associated with gut microbiota metrics in undernourished children, whose gut microbiota were comprised mainly of Proteobacteria, a phylum containing many potentially pathogenic taxa.IMPORTANCE The impact of comprehensive nutritional status, defined as growth, nutritional blood biomarkers, dietary intakes, and feeding practices, on the gut microbiome in children living in low-resource settings has remained underreported in microbiome research. Among undernourished children living in urban slums of Mumbai, India, we observed a high relative abundance of Proteobacteria, a phylum including many potentially pathogenic species similar to the composition in preterm infants, suggesting immaturity of the gut, or potentially a high inflammatory burden. We found head circumference, fat and iron intake, and current breastfeeding were positively associated with microbial diversity, while hemoglobin and weight for length were associated with lower diversity. Findings suggest that examining comprehensive nutrition is critical to gain more understanding of how nutrition and the gut microbiota are linked, particularly in vulnerable populations such as children in urban slum settings.

Acceptability and Adherence to Peanut-Based Energy-Dense Nutritional Supplement Among Adult Malnourished Pulmonary Tuberculosis Patients in Ballabgarh Block of Haryana, India.

BACKGROUND: Undernutrition is a leading risk factor for tuberculosis and is associated with adverse treatment outcomes. Energy-dense nutritional supplement (EDNS) may be helpful in managing undernutrition in tuberculosis patients. METHODS: A longitudinal study was conducted among 102 newly diagnosed pulmonary tuberculosis patients in the Ballabgarh tuberculosis unit in Haryana, India, between September 2018 and February 2019. Participants were provided daily supplementation with 2 sachets of peanut-based EDNS providing 1000 kcal along with the tuberculosis chemotherapy for 2 months. Acceptability was assessed after one month of supplementation. Reported side effects were assessed every 15 days for 2 months and adherence, in terms of proportion of supplement consumed, was assessed on weekly basis for 2 months. Weight was measured at baseline and after 1 month and 2 months. RESULTS: Mean age of participants was 33 years (standard deviation: 13.8) and 75.5% of the participants were male. Almost 100% of the participants found the taste, smell, consistency, and color of the EDNS acceptable. Three participants rejected it after one month of consuming EDNS and another 7 rejected after 2 months of consuming EDNS. After consuming EDNS for 2 months, 13.9% of the participants complained of nausea, 11.9% complained of vomiting, 10.9% complained of diarrhea, and 9.9% complained of pain in the abdomen and abdominal fullness or bloating anytime during the period of supplementation. The adherence to EDNS among the participants was reported as 92.6%. CONCLUSION: A peanut-based EDNS was highly acceptable and safe, and the adherence to it was high among patients with pulmonary tuberculosis.

Immunoglobulin recognition of fecal bacteria in stunted and non-stunted children: findings from the Afribiota study.

BACKGROUND: Child undernutrition is a global health issue that is associated with poor sanitation and an altered intestinal microbiota. Immunoglobulin (Ig) A mediates host-microbial homeostasis in the intestine, and acutely undernourished children have been shown to have altered IgA recognition of the fecal microbiota. We sought to determine whether chronic undernutrition (stunting) or intestinal inflammation were associated with antibody recognition of the microbiota using two geographically distinct populations from the Afribiota project. Fecal bacteria from 200 children between 2 and 5 years old in Antananarivo, Madagascar, and Bangui, Central African Republic (CAR), were sorted into IgA-positive (IgA+) and IgA-negative (IgA-) populations by flow cytometry and subsequently characterized by 16S rRNA gene sequencing to determine IgA-bacterial targeting. We additionally measured IgG+ fecal bacteria by flow cytometry in a subset of 75 children. RESULTS: Stunted children (height-for-age z-score ≤ -2) had a greater proportion of IgA+ bacteria in the fecal microbiota compared to non-stunted controls. This trend was consistent in both countries, despite the higher overall IgA-targeting of the microbiota in Madagascar, but lost significance in each country individually. Two of the most highly IgA-recognized bacteria regardless of nutritional status were Campylobacter (in CAR) and Haemophilus (in both countries), both of which were previously shown to be more abundant in stunted children; however, there was no association between IgA-targeting of these bacteria and either stunting or inflammatory markers. IgG-bound intestinal bacteria were rare in both stunted and non-stunted children, similar to levels observed in healthy populations. CONCLUSIONS: Undernourished children carry a high load of intestinal pathogens and pathobionts. Our data suggest that stunted children have a greater proportion of IgA-recognized fecal bacteria. We moreover identify two putative pathobionts, Haemophilus and Campylobacter, that are broadly targeted by intestinal IgA. This study furthers our understanding of host-microbiota interactions in undernutrition and identifies immune-recognized microbes for future study.