Disrupted development of the gut microbiota is a contributing cause of childhood malnutrition. Bifidobacterium longum subspecies infantis is a prominent early colonizer of the infant gut that consumes human milk oligosaccharides (HMOs). We found that the absolute abundance of Bifidobacterium infantis is lower in 3- to 24-month-old Bangladeshi infants with severe acute malnutrition (SAM) compared to their healthy age-matched counterparts. A single-blind, placebo-controlled trial (SYNERGIE) was conducted in 2- to 6-month-old Bangladeshi infants with SAM. A commercial U.S. donor–derived B. infantis strain (EVC001) was administered daily with or without the HMO lacto- N -neotetraose for 28 days. This intervention increased fecal B. infantis abundance in infants with SAM, although to levels still 10- to 100-fold lower than in untreated healthy controls. EVC001 treatment promoted weight gain that was associated with reduced intestinal inflammation markers in infants with SAM. We cultured fecal B. infantis strains from Bangladeshi infants and colonized gnotobiotic mice with these cultured strains. The gnotobiotic mice were fed a diet representative of that consumed by 6-month-old Bangladeshi infants, with or without HMO supplementation. One B. infantis strain, Bg_2D9, expressing two gene clusters involved in uptake and utilization of N -glycans and plant-derived polysaccharides, exhibited superior fitness over EVC001. The fitness advantage of Bg_2D9 was confirmed in a gnotobiotic mouse model of mother-to-infant gut microbiota transmission where dams received a pretreatment fecal community from a SAM infant in the SYNERGIE trial. Whether Bg_2D9 is superior to EVC001 for treating malnourished infants who consume a diet with limited breastmilk requires further clinical testing.

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.

Human milk oligosaccharides (HMOs) support the development of a healthy gut microbiome and the growth of infants. We aimed to determine the association of different HMOs with severe acute malnutrition (SAM) among Bangladeshi young infants. This study was nested within a single-blind, randomized, pilot clinical trial (NCT0366657). A total of 45 breastmilk samples from mothers of < 6 months old infants who had SAM (n = 26) or were non-malnourished (n = 19) and were analyzed for constituent HMOs. Of the infants with SAM, 14 (53.85%) had secretor mothers, and 11 (57.89%) of the non-malnourished infants had secretor mothers. A one-unit increase in the relative abundance of sialylated HMOs was associated with higher odds of SAM in age and sex adjusted model (aOR = 2.00, 90% CI 1.30, 3.06), in age, sex, and secretor status adjusted model (aOR = 1.96, 90% CI 1.29, 2.98), and also in age and sex adjusted model among non-secretor mothers (aOR = 2.86, 90% CI 1.07, 7.62). In adjusted models, there was no evidence of a statistically significant association between SAM and fucosylated or undecorated HMOs. Our study demonstrates that a higher relative abundance of sialylated HMOs in mothers’ breastmilk may have a negative impact on young infants’ nutritional status.

Background Severe acute malnutrition (SAM) and environmental enteric dysfunction (EED) are highly prevalent among children residing in resource-limited countries like Bangladesh. L-carnitine may play a role in improving the growth and ameliorating the EED among nutritionally vulnerable children. Objective To investigate the role of L-carnitine supplementation on the rate of weight gain, duration of hospital stays, and EED biomarkers among children with severe acute malnutrition. Methods This study is a double-blinded, placebo-controlled, randomized clinical trial aiming to enroll diarrheal children with SAM between 9–24 months of both sexes attending the nutritional rehabilitation unit (NRU) of Dhaka Hospital of icddr,b. It is an ongoing trial including two arms where one arm receives L-carnitine supplementation, and the other arms receive a placebo for 15 days in addition to the existing standard treatment of SAM. The primary outcome is the rate of weight gain, and the secondary outcomes include duration of hospital stay and EED biomarkers. Outcomes are assessed at baseline and 15 days of post-intervention. We hypothesize that the L- carnitine supplementation for 15 days in children with SAM will improve the rate of weight gain and biomarkers of EED. Trial registration ClinicalTrials.gov # NCT05083637. Date of registration: October 19, 2021.

Both wasting and undernutrition are responsible for multiple morbidities and increased mortality in younger children hospitalized for acute illnesses. The question of whether children who are suffering from severe underweight are as vulnerable as children suffering from severe wasting needs to be researched further. We aimed to compare the morbidity and mortality of severely underweight but not severely wasted (SU-nSW) children with that of severely wasted (SW) children admitted to inpatient wards of a hospital. Data from 12,894 children aged < 5 years were collected using cross-sectional methods from Dhaka Hospital, International Centre for Diarrhoeal Disease Research, Bangladesh between March 2019 and December 2021. After exclusion of non-desired populations (N = 8,834), comparisons between SU-nSW (N = 1,876) and SW (N = 2,184) children were observed. The risk of morbidities and mortality among SU-nSW and SW children was analyzed after adjusting for age and sex. Inpatient morbidities were mostly similar among children with sepsis (adjusted odds ratio [aOR]: 0.90; 95% CI: 0.69, 1.19; P = 0.472) and convulsions (aOR: 0.84; 95% CI: 0.51, 1.37; P = 0.475). Dehydration (aOR: 0.71; 95% CI: 0.62, 0.81; P < 0.001) and hypokalemia (aOR: 0.58; 95% CI: 0.42, 0.79; P = 0.001) were more likely associated with SW children than with SU-nSW children. Pneumonia/severe pneumonia was more likely to affect SU-nSW children (aOR: 1.24; 95% CI: 1.02, 1.48; P = 0.018). Death was comparable between the two groups (aOR: 1.32; 95% CI: 0.70, 2.49; P = 0.386). This study underscores the importance of implementing present treatment guidelines for severe acute malnutrition in the facility-based management of severely underweight children as well.