Table 1.

Randomized, double-blind,placebo-controlled trials examining microbiome-targeting therapies in the treatment of malnourished children

Microbiome-Targeting Therapy	Study Population	Primary Outcome	Secondary Outcomes	Reference
(Super Synbiotics AB, Stockholm, Sweden)a in RUTF vs RUTF alone for treatment duration (mean 33 d)	N = 795, 5 mo–168 mo with WFH <70%, nutritional edema, or MUAC <11 cm, receiving inpatient treatment in Blantyre, Malawi	No effect on nutritional cure (WFH >80% on 2 consecutive outpatient visits): 53.9% treatment vs 51.3% placebo, P = .40	No effect on mortality, outpatient defaulting, treatment failures, hospital readmissions, loss to followup, rate of weight gain, or days to nutritional cure	Kerac et al,93 2009
Amoxicillin (80–90 mg/kg/d) vs cefdinir (14 mg/kg/d) vs placebo in 2 daily doses during the initial 7 d of RUTF	N = 2767, 6 mo–59 mo with nutritional edema or WHZ < −3 and able to consume RUTF as outpatient therapy at 18 feeding clinics in rural Malawi	Placebo increased risk of treatment failure vs amoxicillin (RR 1.32; 95% CI, 1.04–1.68) and vs cefdinir (RR 1.64; 95% CI, 1.27–2.11) and risk of death vs amoxicillin (RR 1.55; 95% CI, 1.07–2.24) and vs cefdinir (RR 1.80; 95% CI, 1.22–2.64)	Placebo decreased rate of weight gain vs cefdinir (3.1 ± 4.1 vs 3.9 ± 6.3 g/kg/d, P = .002); placebo decreased rate of MUAC gain (0.22±0.41 mm/d) vs amoxicillin (0.27 ± 0.42 mm/d, P = .01) and vs cefdinir (0.28 ± 0.42 mm/d, P = .002); no effect on time to recovery or rate of gain of length/height	Trehan et al,89 2013
Amoxicillin (80 mg/kg/d) vs placebo twice daily for 7 d	N = 2412, 6 mo–59 mo with WHZ < −3 or MUAC <115 mm (but no nutritional edema), in outpatient therapy at 4 health centers in rural Niger	No effect on nutritional recovery (WHZ ≥ −2 on 2 consecutive visits and MUAC ≥115 and no nutritional edema ≥7 d and all treatments completed) by 8 wk of followup, risk ratio for amoxicillin vs placebo 1.05; 95% CI, 0.99–1.12	Amoxicillin decreased risk of hospital admission by 14%; no effect on nonresponse rate at 8 wk, death from any cause, or default	Isanaka et al,91 2016
Cotrimoxazole (120 mg/d for age <6 mo or 240 mg/d for age 6 mo to 5 y) vs placebo daily for 6 mo	N = 1778, 60 d–59 mo with MUAC <115 mm (≥6 mo) or <110 mm (2–5 mo) or nutritional edema, and HIV-antibody rapid test negative and completed initial stabilization phase of treatment at 2 rural and 2 urban hospitals in Kenya	No effect on mortality during the 365-d study period, hazard ratio for cotrimoxazole vs placebo 0.90; 95% CI, 0.71–1.16	Cotrimoxazole increased incidence of diarrhea and decreased incidence of confirmed malaria, skin or soft tissue infections, and positive urine culture; no effect on frequency of other nonfatal illness episodes, pathogens detected from blood culture, suspected toxic effects, or changes in anthropometric or hematological indices	Berkley et al,92 2016
Bifidobacterium animalis subsp lactis and Lactobacillus rhamnosus (109 CFUs/d) vs placebo from admission to completion of outpatient treatment (range 8–12 wk)	N = 400, 6 mo–59 mo with MUAC <115 mm or WHZ/WLZ < −3 or nutritional edema, in inpatient therapy in Kampala, Uganda	No effect on mean duration of diarrhea, adjusted effect size for probiotics vs placebo during inpatient treatment +0.2; 95% CI, −0.8 d-1.2 d	Probiotics decreased duration of diarrhea vs placebo (−2.2 d; 95% CI −3.5–0.3); no effect on incidence or severity of diarrhea, pneumonia incidence or duration or severity, nutritional recovery, weight gain, fever, vomiting, duration of hospitalization, or mortality	Grenov et al,94 2017

Abbreviations: CFUs, colony-forming units; RR, relative risk; WFH, weight-for-height as mean of National Center for Health Statistics data.

^aFreeze-dried 10¹¹ CFUs Pediococcus pentosaceus, Leuconostoc mesenteroides, Lactobacillus paracasei, and Lactobacillus plantarum; 2.5 g each of oat bran, inulin, pectin, and resistant starch.