Alternative proteins support somatic and muscular development while remodeling the microbiome in zebrafish

Protein intake is fundamental to growth, well-being and long-term health. Unfortunately, many diets rely upon animal-based proteins, which are environmentally costly. To feed a growing population, alternative protein sources will be necessary. To determine the health implications of switching entirely away from animal-based diets, we fed alternative proteins to a model vertebrate during development. Zebrafish were fed diets including protein from fishmeal, pea, milk and whey, and their growth and health were monitored. Most diets supported growth, with the exception of those high in whey and milk protein, which resulted in fish that were ∼10% shorter in body length and had muscle fibers ∼30% smaller than control. Of interest, genes associated with insulin sensitivity and fat storage were upregulated in some diets (<i>lepr</i>, 2 to 3.5 fold, and <i>fasn</i>, 2.5 to 4 fold, respectively). The microbiome changed dramatically between animal and alternative proteins, shifting from Fusobacteriota to Proteobacteria dominance, with <i>Cetobacterium</i> positively affecting health, and <i>Aeromonas</i> doing the opposite. Our findings indicate that more environmentally friendly diets can lead to healthy outcomes, but that the protein source is critically important.