Host Fecal mRNAs Predicted Environmental Enteric Dysfunction among Children with Moderate Acute Malnutrition in Sierra Leone

Singh, Akriti; Potani, Isabel; Griswold, Stacy; Suri, Devika; Langlois, Breanne K.; Shen, Ye; Walton, Shelley; Chui, Kenneth; Manary, Mark; Webb, Patrick; Rogers, Beatrice Lorge; Rosenberg, Irwin H.

doi:10.4269/ajtmh.21-0348

Cited by 3 publications

(3 citation statements)

References 23 publications

(41 reference statements)

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Section: Introductionmentioning

confidence: 99%

“…Changes in microorganism colonisation of the gut for children suffering from MAM can be assessed by 16S and 18S mRNA amplification and sequencing. Species identification can be conducted using a specialised database like SYLVA (Singh et al, 2021 ). Adequate management of malnutrition should therefore include addressing food, micronutrient supplementation and regulation of intestinal flora with, for example, broad‐spectrum antibiotic therapy (Trehan et al, 2013 ).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Three‐arm clinical trial of improved flour targeting intestinal microbiota (MALINEA)

Vray,

Tondeur,

Hedible

et al. 2024

Maternal & Child Nutrition

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The main objective of this project was to compare in the field conditions two strategies of re‐nutrition of children with moderate acute malnutrition (MAM) aged from 6 to 24 months, targeting the microbiota in comparison with a standard regimen. A three‐arm, open‐label, pragmatic randomised trial was conducted in four countries (Niger, CAR, Senegal and Madagascar). Children received for 12 weeks either fortified blended flour (FBF control) = arm 1, or FBF + azithromycin (oral suspension of 20 mg/kg/day daily given with a syringe) for the first 3 days at inclusion = arm 2 or mix FBF with inulin/fructo‐oligosaccharides (6 g/day if age ≥12 months and 4 g if age <12 months) = arm 3. For each arm, children aged from 6 to 11 months received 100 g x 2 per day of flours and those aged from 12 to 24 months received 100 g × 3 per day of FBF. The primary endpoint was nutritional recovery, defined by reaching a weight‐for‐height z‐score (WHZ) ≥ −1.5 within 12 weeks. Overall, 881 children were randomised (297, 290 and 294 in arm 1, arm 2 and arm 3, respectively). Three hundred and forty‐four children were males (39%) and median/mean age were 14.6/14.4 months (SD = 4.9, IQR = 10.5–18.4). At inclusion, the three arms were comparable for all criteria, but differences were observed between countries. Overall, 44% (390/881) of the children recovered at week 12 from MAM, with no significant difference between the three arms (41.4%, 45.5% and 45.9%, in arm 1, arm 2 and arm 3, respectively, p = 0.47). This study did not support the true advantages of adding a prebiotic or antibiotic to flour. When using a threshold of WHZ ≥ −2 as an exploratory endpoint, significant differences were observed between the three arms, with higher success rates in arms with antibiotics or prebiotics compared to the control arm (66.9%, 66.0% and 55.2%, respectively, p = 0.005).

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Three‐arm clinical trial of improved flour targeting intestinal microbiota (MALINEA)

Vray,

Tondeur,

Hedible

et al. 2024

Maternal & Child Nutrition

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“…These mRNA transcripts have been described and measured in populations of rural infants and children in Malawi and Sierra Leone, where they showed promise as indicators of EED based on their association with L:M test results and inflammatory indicators [20][21][22][23][24][25]. However, several questions remain about the use of these biomarkers for the assessment of EED.…”

Section: Introductionmentioning

confidence: 99%

Stool biomarkers as measures of enteric pathogen infection in infants from Addis Ababa informal settlements

et al. 2023

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Frequent enteric infections in children may be an important cause of growth faltering; however, we do not fully understand the mechanisms by which pathogen infections and the physiological responses to these infections result in poorer growth. Commonly used protein fecal biomarkers (anti-alpha trypsin, neopterin, and myeloperoxidase) provide broad immunological information on an inflammatory response; however, they do not provide information on non-immune processes (e.g., gut integrity) that may be important indicators of chronic end states such as environmental enteric dysfunction (EED). To explore how additional biomarkers will better inform which physiological pathways (both immune and non-immune) are impacted by pathogen exposure we added to the traditional panel of 3 protein fecal biomarkers 4 novel fecal mRNA transcript biomarkers (sucrase isomaltase, caudal homeobox 1, S100A8, and mucin 12) and analyzed stool samples from infants living in informal settlements in Addis Ababa, Ethiopia. To test how this expanded biomarker panel captures distinct pathogen exposure processes we used two different scoring systems. First, we used a theory-based approach to assign each biomarker to specific physiological attributes based on prior understanding of each biomarker. Second, we used data reduction methods to categorize biomarkers and then assign physiological attributes to those categories. We used linear models to examine the association between the derived biomarker scores (based on mRNA and protein levels) and stool pathogen gene counts to determine pathogen specific effects on gut physiology and immune responses. Inflammation scores were positively associated with Shigella and enteropathogenic E.Coli (EPEC) infection, while gut integrity scores were negatively associated with Shigella, EPEC and, shigatoxigenic E.coli (STEC) infection. Our expanded panel of biomarkers hold promise as tools to measure systemic outcomes of enteric pathogen infection. mRNA biomarkers complement established protein biomarkers by providing important cell-specific physiological and immunological consequences of pathogen carriage that can lead to chronic end states such as EED.

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Review article: Faecal biomarkers for assessing small intestinal damage in coeliac disease and environmental enteropathy

Kivelä,

Lindfors,

Lundin

et al. 2024

Aliment Pharmacol Ther

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SummaryBackgroundIn coeliac disease and environmental enteropathy, dietary gluten and enteric infections cause reversible inflammation and morphological changes to the small intestinal mucosa that can be detected in biopsy samples obtained by endoscopy. However, there is a clear need for non‐invasive biomarkers. Constant shedding of mucosal material into the bowel lumen and faeces, together with easy availability of stool, makes it an interesting sample matrix.AimsTo conduct a systematic literature search and summarize the existing evidence for host mucosa‐derived faecal biomarkers in evaluating small intestinal damage.MethodsWe searched for studies on PubMed (MEDLINE) until 1 March 2024.ResultsWe identified 494 studies and included 35 original case–control and cohort studies. These assessed host mucosal transcripts and 14 other markers aiming specifically to reflect inflammation and cell‐mediated, innate and gluten‐induced immune responses. In coeliac disease, faecal calprotectin and anti‐gliadin, tissue transglutaminase, endomysium and deamidated gliadin peptide antibodies were the most studied but with inconsistent results. Single studies reported positive findings about microRNA transcripts, β‐defensin‐2, lipocalin‐2, zonulin‐related proteins and angiotensin‐converting enzyme. In environmental enteropathy, a non‐significant association was reported between calprotectin and urine lactulose/mannitol ratio; there were conflicting results for neopterin, myeloperoxidase and host transcripts. Single studies reported a positive association for lactoferrin, and a negative association for regenerating islet‐derived protein 1. Studies comparing faecal markers against small intestinal biopsy findings were not identified in environmental enteropathy.ConclusionsFurther studies are needed to determine reliable faecal markers as a proxy for small intestinal mucosal damage.

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Host Fecal mRNAs Predicted Environmental Enteric Dysfunction among Children with Moderate Acute Malnutrition in Sierra Leone

Cited by 3 publications

References 23 publications

Three‐arm clinical trial of improved flour targeting intestinal microbiota (MALINEA)

Three‐arm clinical trial of improved flour targeting intestinal microbiota (MALINEA)

Stool biomarkers as measures of enteric pathogen infection in infants from Addis Ababa informal settlements

Review article: Faecal biomarkers for assessing small intestinal damage in coeliac disease and environmental enteropathy

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