Suboptimal refeeding compensates stunting in a mouse model of juvenile malnutrition.

Abstract

Background: Early postnatal life is a critical period of rapid growth in mammals, heavily reliant on adequate nutrition. Protein-energy malnutrition (PEM) during this window can lead to stunting and wasting, with lasting health consequences.

Objective: This study developed a mouse model of juvenile PEM to assess the effects of refeeding with various diets and interventions on growth recovery, including probiotic supplementation and suboptimal refeeding diets. Outcomes included length and weight catch-up, organ weights, and glucose tolerance.

Methods: Juvenile male and female C57Bl/6J mice (N = 8-11/group) were fed a low-protein diet (LPD, 5% kcal from protein) starting at postnatal day 14 (P14) to which the pups and dams had access. Following weaning, mice were refed an optimal diet (27% kcal from protein) at different times (P28 to P56). Male mice received additional interventions, including supplementation with Lactiplantibacillus plantarum WJL (Lp^WJL) during refeeding, or refeeding with a Western diet (WD, 15.3% kcal from protein) or a modified Western diet (MWD, 7.5% kcal from protein). Statistical analyses used ANOVA, ANCOVA, and PCA.

Results: Optimal refeeding restored growth in females (body weight in optimal-fed: 20.5 ± 0.3 g vs 19.4 ± 0.6 g in P56-refed), but males showed persistent stunting (26.8 ± 0.7 g vs 21.9 ± 0.9 g; P < 0.05). In males, Lp^WJL did not enhance growth recovery and exacerbated glucose intolerance in suboptimal refeeding groups. Males refed WD or MWD restored body length but showed impaired glucose metabolism, particularly in mice refed WD, with glycemia 30 minutes after glucose challenge reaching 20.4 ± 4.0 mM vs 14.3 ± 3.0 mM in optimal-fed mice (P < 0.05).

Conclusion: Sex-dependent differences in recovery from PEM were evident, with males showing incomplete growth recovery despite optimal refeeding. Suboptimal diets compensated for stunting but impaired glucose metabolism, and Lp^WJL did not improve growth outcomes.