Globally, stunting affects ∼150 million children under five, while wasting affects nearly 50 million. Current interventions have had limited effectiveness in ameliorating long-term sequelae of undernutrition including stunting, cognitive deficits and immune dysfunction. Disrupted development of the gut microbiota has been linked to the pathogenesis of undernutrition, providing potentially new treatment approaches. 124 Bangladeshi children with moderate acute malnutrition (MAM) enrolled (at 12-18 months) in a previously reported 3-month RCT of a microbiota-directed complementary food (MDCF-2) were followed for two years. Weight and length were monitored by anthropometry, the abundances of bacterial strains were assessed by quantifying metagenome-assembled genomes (MAGs) in serially collected fecal samples and levels of growth-associated proteins were measured in plasma. Children who had received MDCF-2 were significantly less stunted during follow-up than those who received a standard ready-to-use supplementary food (RUSF) [linear mixed-effects model, β_{treatment group x study week} (95% CI) = 0.002 (0.001, 0.003); P = 0.004]. They also had elevated fecal abundances of Agathobacter faecis, Blautia massiliensis, Lachnospira and Dialister, plus increased levels of a group of 37 plasma proteins (linear model; FDR-adjusted P < 0.1), including IGF-1, neurotrophin receptor NTRK2 and multiple proteins linked to musculoskeletal and CNS development, that persisted for 6-months post-intervention. MDCF-2 treatment of Bangladeshi children with MAM, which produced significant improvements in wasting during intervention, also reduced stunting during follow-up. These results suggest that the effectiveness of supplementary foods for undernutrition may be improved by including ingredients that sponsor healthy microbiota-host co-development. This work was supported by the BMGF (Grants OPP1134649/INV-000247).

Severe acute malnutrition (SAM) is a major global public health problem. We aimed to assess the effects of probiotic and synbiotic supplementation on rate of weight gain and change in length in young SAM infants. This study was substudy of a single-blind randomized clinical trial (NCT0366657). During nutritional rehabilitation, 67 <6 months old SAM infants were enrolled and randomized to receive either probiotic (Bifidobacterium. infantis EVC001) or synbiotic (B. infantis EVC001 + Lacto-N-neotetraose [LNnT]) or placebo (Lactose) for four weeks and were followed for four more weeks after supplementation. In multivariable linear regression model, the mean rate of weight gain in the probiotic arm compared to placebo was higher by 2.03 unit (P < 0.001), and 1.13 unit (P = 0.030) in the synbiotic arm. In linear mixed-effects model, mean WAZ was higher by 0.57 unit (P = 0.018) in probiotic arm compared to placebo. Although not statistically significant, delta length for age z score (LAZ) trended to be higher among children in probiotc (β = 0.25) and synbiotic (β = 0.26) arms compared to placebo in multivariable linear regression model. Our study describes that young SAM infants had a higher rate of weight gain when supplemented with probiotic alone, compared to their counterparts with either synbiotic or placebo.

Background: In April 2018, a diarrhea epidemic broke out in Dhaka city and adjoining areas, which continued through May. The Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), a dedicated diarrheal disease hospital, had a large upsurge in patient visits during the epidemic. An enhanced understanding of the epidemiology of this epidemic may help health-related professionals better prepare for such events in the future. This study examined the microbial etiology and non-pathogen factors associated with diarrhea during the epidemic. The study also evaluated the patients’ presentation and clinical course and estimated the potential mortality averted by treating patients during the epidemic. Methodology/Principal findings: Data from the patients who were treated at Dhaka Hospital during the diarrhea epidemic between April 2 and May 12, 2018 and were enrolled into the Diarrheal Disease Surveillance System (DDSS) at icddr,b were compared with the DDSS-enrolled patients treated during the seasonally-matched periods in the flanking years using logistic regression. icddr,b Dhaka Hospital treated 29,212 diarrheal patients during the 2018 epidemic period (and 25,950 patients per comparison period on average). Vibrio cholerae was the most common pathogen isolated (7,946 patients; 27%) and associated with diarrhea during the epidemic (adjusted odds ratio [AOR] 1.5, 95% CI: 1.1–2.0). The interaction of Vibrio cholerae with ETEC (AOR 2.7, 95% CI: 1.3–5.9) or Campylobacter (AOR 2.4, 95% CI: 1.1–5.1) was associated with further increased odds of diarrhea during the epidemic. In children under five years old, rotavirus was the most common pathogen (2,029 patients; 26%). Those who were adolescents (AOR 2.0, 95% CI: 1.3–3.1) and young adults (AOR 1.9, 95% CI: 1.4–2.5) compared to children younger than five years, resided within a 10 km radius of Dhaka Hospital (AOR 1.6, 95% CI: 1.1–2.2) compared to those living outside 20 km, borrowed money or relied on aid to pay for the transport to the hospital (AOR 1.6, 95% CI: 1.2–2.0), used tap water (AOR 1.8, 95% CI: 1.4–2.4) for drinking compared to tubewell water, and disposed of the solid waste directly outside the house (AOR 4.0, 95% CI: 2.7–5.9) were more likely to present with diarrhea during the epidemic. During the epidemic, patients were more likely to present with severe dehydration (odds ratio [OR] 1.6, 95% CI: 1.3–2.0) and require inpatient admission (OR 2.5, 95% CI: 1.9–3.3), intravenous rehydration (OR 1.7, 95% CI: 1.4–2.1), and antibiotics (OR 2.2, 95% CI: 1.8–2.7). The in-hospital case fatality rate was low (13 patients; 0.04%), and the hospital averted between 12,523 and 17,265 deaths during the epidemic. Conclusions/Significance: Vibrio cholerae played the primary role in the 2018 diarrhea epidemic in Dhaka. Campylobacter, enterotoxigenic Escherichia coli, and rotavirus had a secondary role. Adolescents and adults, residents of the metropolitan area, and those who were relatively poor and lacked safe water, sanitation, and hygiene (WASH) practices comprised the most vulnerable groups. Despite the increased disease severity during the epidemic, the case fatality rate was less than 0.1%. icddr,b Dhaka Hospital saved as many as 17,265 lives during the epidemic.

To estimate the effect of inadequate maternal weight gain in the third trimester on the risk of intrauterine growth restriction (IUGR) in rural Bangladesh. This study analyzed data from 1,463 mother-infant pairs in Matlab, Bangladesh which were available through the electronic databases of Matlab Health and Demographic Surveillance System and Matlab hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b). All the mothers were admitted to Matlab hospital for childbirth from January 2012 to December 2014, and they had singleton live births at term. Third-trimester weight gain (kg) was calculated by subtracting the estimated weight at the end of the second trimester from the weight taken before childbirth. Inadequate third-trimester weight gain was defined as 4 kg or less irrespective of pre-gravid nutritional status. IUGR was defined as a birth weight below 2500 g in full-term newborns (LBW-Term), and a birth weight for gestational age and infant sex less than the 10^th percentile (SGA-10^th) and 2 standard deviations below the mean birth weight (SGA-2SD) based on the international newborn standards from the INTERGROWTH-21^st project. Multivariable logistic regression models were fitted to determine the independent effect of inadequate weight gain in the third trimester on the risk of IUGR. A total of 824 (56.3%) women experienced inadequate weight gain in the third trimester of pregnancy. In this study, 215 (14.7%), 573 (39.2%) and 220 (15.0%) infants were born as LBW-Term, SGA-10^th and SGA-2SD, respectively. In the multivariable logistic regression models, compared to adequate weight gain in the third-trimester, the odds ratios (OR) for LBW-Term, SGA-10^th and SGA-2SD for inadequate weight gain were 1.8 (95% CI: 1.3, 2.5; p < 0.001), 1.4 (95% CI: 1.1, 1.8; p = 0.002) and 1.8 (95% CI: 1.3, 2.4; p = 0.001), respectively. Both inadequate third-trimester weight gain and IUGR are prevailing public health concerns in rural Bangladesh. Inadequate weight gain in the third trimester substantially increased the risk of IUGR. Public health programs focusing on the promotion of adequate weight gain in the third trimester of pregnancy with an ultimate aim to decrease IUGR should be implemented.

Escherichia coli (E. coli) pathotypes are the most common cause of diarrhea, especially in developing countries. Environmental Enteric Dysfunction (EED) is presumed to be the result of infection with one or more pathotypes and can affect intestinal health and childhood growth. We sought to investigate the association of E. coli pathotypes infection with biomarkers of EED and nutritional status among slum-dwelling malnourished children in Bangladesh. This study comprised a total of 1050 stunted and at risk of stunting children. TaqMan Array Card assays were used to determine the presence of E. coli pathotypes in feces. Prevalence of infection with EAEC was highest (68.8%) in this cohort of children, followed by EPEC (55.9%), ETEC (44%), Shigella/EIEC (19.4%) and STEC (3.2%). The levels of myeloperoxidase and calprotectin were significantly higher in EAEC (P=0.02 and P=0.04), EPEC (P=0.02 and P=0.03) and Shigella/EIEC (P=0.05 and P=0.02) positive participants while, only calprotectin was significantly higher in ETEC (P=0.01) positive participants. Reg1B was significantly higher in participants with EAEC (P=0.004) while, neopterin levels were significantly lower in ETEC (P=0.003) and Shigella/EIEC (P=0.003) positive cases. A significant positive relationship was observed between EAEC and fecal levels of Reg1B (β = 0.28; 95% CI = 0.12, 0.43; p-value<0.001). Besides, ETEC was found to be positively and significantly associated with the levels of calprotectin (β = 0.14; 95 percent CI = 0.01, 0.26; p-value=0.037) and negatively with neopterin (β = -0.16; 95% CI = -0.30, -0.02; p-value=0.021). On the other hand, infection with EPEC was found to be negatively associated with length-for-age (β = -0.12; 95% CI = -0.22, -0.03; p-value=0.011) and weight-for-age (β = -0.11; 95% CI = -0.22, -0.01; p-value=0.037). The study findings suggest that infection with certain E. coli pathotypes (EAEC and ETEC) influences gut health and EPEC is associated with linear growth and underweight in Bangladeshi children.