Spontaneous hypopigmentation mutant in threespine stickleback fish exhibits changes in the gut microbiome consistent with inflammatory bowel diseases.

Abstract

Albinism is a large group of disorders characterized by a loss of pigment in ectoderm-derived tissues - most noticeably impacting the skin, hair, and eyes. Albinism is categorized as either syndromic or non-syndromic. Syndromic albinisms include a wide range of disorders with mutations impacting not just pigmentation but other cellular functions. These include, non-exclusively, melanogenesis disorders, endosome trafficking disorders like lysosomal storage disorders, and cell migration disorders. Mutations leading to syndromic albinisms can cause multi-organ system symptoms due to broad disruption lysosome related organelles (LROs) function. Various genetic mutations impact biogenesis, cell maturation, or trafficking at different stages which can lead to a range of severity. Syndromic albinisms also present with different combinations of symptoms depending on the impacted organelles; including oculocutaneous albinism (OCA) (melanosomes), blood diathesis (platelet dense granules), pulmonary fibrosis (lamellar bodies), or chronic inflammation (multiple cellular sources). Animal models for these multisymptomatic complex disorders are needed to understand the effects on systemic health. One such area of interest is in gut health of those with syndromic albinism. Shared inflammatory patterns of syndromic albinisms like Hermansky-Pudlak Syndromes (HPS) and Inflammatory Bowel Disease (IBD) are well studied, with animal models of HPS jointly used to study patterns of inflammation in IBD. However, the impact of this shared gastrointestinal inflammation on the gut microbiome remains unexplored. Using a spontaneously identified mutant family of threespine stickleback fish, we characterize phenotypes consistent with oculocutaneous albinism and vision impairment and demonstrate shared features of gut health to IBD extend from inflammation to the gut microbiome. We argue syndromic albinism models should be explored as models to study the gut microbiome in addition to inflammatory phenotypes in IBD, and importantly, be used to test microbial/dietary interventions for both IBD and syndromic albinisms.