Induced Immune Reaction in the Acorn Worm, Saccoglossus kowalevskii, Informs the Evolution of Antiviral Immunity.

Evolutionary perspectives on the deployment of immune factors following infection have been shaped by studies on a limited number of biomedical model systems with a heavy emphasis on vertebrate species. Although their contributions to contemporary immunology cannot be understated, a broader phylogenetic perspective is needed to understand the evolution of immune systems across Metazoa. In our study, we leverage differential gene expression analyses to identify genes implicated in the antiviral immune response of the acorn worm hemichordate, Saccoglossus kowalevskii, and place them in the context of immunity evolution within deuterostomes-the animal clade composed of chordates, hemichordates, and echinoderms. Following acute exposure to the synthetic viral double-stranded RNA analog, poly(I:C), we show that S. kowalevskii responds by regulating the transcription of genes associated with canonical innate immunity signaling pathways (e.g., nuclear factor κB and interferon regulatory factor signaling) and metabolic processes (e.g., lipid metabolism), as well as many genes without clear evidence of orthology with those of model species. Aggregated across all experimental time point contrasts, we identify 423 genes that are differentially expressed in response to poly(I:C). We also identify 147 genes with altered temporal patterns of expression in response to immune challenge. By characterizing the molecular toolkit involved in hemichordate antiviral immunity, our findings provide vital evolutionary context for understanding the origins of immune systems within Deuterostomia.

Longitudinal Analysis of the Intestinal Microbiota in the Obese Mangalica Pig Reveals Alterations in Bacteria and Bacteriophage Populations Associated With Changes in Body Composition and Diet.

Due to its immunomodulatory potential, the intestinal microbiota has been implicated as a contributing factor in the development of the meta-inflammatory state that drives obesity-associated insulin resistance and type 2 diabetes. A better understanding of this link would facilitate the development of targeted treatments and therapies to treat the metabolic complications of obesity. To this end, we validated and utilized a novel swine model of obesity, the Mangalica pig, to characterize changes in the gut microbiota during the development of an obese phenotype, and in response to dietary differences. In the first study, we characterized the metabolic phenotype and gut microbiota in lean and obese adult Mangalica pigs. Obese or lean groups were created by allowing either ad libitum (obese) or restricted (lean) access to a standard diet for 54 weeks. Mature obese pigs were significantly heavier and exhibited 170% greater subcutaneous adipose tissue mass, with no differences in muscle mass compared to their lean counterparts. Obese pigs displayed impaired glucose tolerance and hyperinsulinemia following oral glucose challenge, indicating that a metabolic phenotype also manifested with changes in body composition. Consistent with observations in human obesity, the gut microbiota of obese pigs displayed altered bacterial composition. In the second study, we characterized the longitudinal changes in the gut microbiota in response to diet and aging in growing Mangalica pigs that were either limit fed a standard diet, allowed ad libitum access to a standard diet, or allowed ad libitum access to a high fat-supplemented diet over an 18-week period. As expected, weight gain was highest in pigs fed the high fat diet compared to ad libitum and limit fed groups. Furthermore, the ad libitum and high fat groups displayed significantly greater adiposity consistent with the development of obesity relative to the limit fed pigs. The intestinal microbiota was generally resilient to differences in dietary intake (limit fed vs ad libitum), though changes in the microbiota of pigs fed the high fat diet mirrored changes observed in mature obese pigs during the first study. This is consistent with the link observed between the microbiota and adiposity. In contrast to intestinal bacterial populations, bacteriophage populations within the gut microbiota responded rapidly to differences in diet, with significant compositional changes in bacteriophage genera observed between the dietary treatment groups as pigs aged. These studies are the first to describe the development of the intestinal microbiota in the Mangalica pig, and are the first to provide evidence that changes in body composition and dietary conditions are associated with changes in the microbiome of this novel porcine model of obesity.

Maternal Dietary Protein Intake Influences Milk and Offspring Gut Microbial Diversity in a Rat (Rattus norvegicus) Model.

Historically, investigators have assumed microorganisms identified in mother's milk to be contaminants, but recent data suggest that milk microbiota may contribute to beneficial maternal effects. Microorganisms that colonize the gastrointestinal tracts of newborn mammals are derived, at least in part, from the maternal microbial population. Milk-derived microbiota is an important source of this microbial inocula and we hypothesized that the maternal diet contributes to variation in this microbial community. To evaluate the relationship between a mother's diet and milk microbiome, we fed female rats a low- or high-protein diet and mated all individuals. Milk and cecal contents were collected from dams at peak lactation (14-day post-partum), and the bacterial composition of each community was assessed by 16S rRNA gene amplicon sequencing. Our findings revealed higher dietary protein intake decreased fecal microbial diversity but increased milk microbial and pup cecum diversity. Further, the higher dietary protein intake resulted in a greater abundance of potentially health-promoting bacteria, such as Lactobacillus spp. These data suggest that dietary protein levels contribute to significant shifts in the composition of maternal milk microbiota and that the functional consequences of these changes in microbial inocula might be biologically important and should be further explored.