Many alcohol-induced health complications are directly attributable to the toxicity of alcohol or its metabolites, but another potential health impact of alcohol may be on the microbial communities of the human gut. Clear distinctions between healthy and diseased-state gut microbiota have been observed in subjects with metabolic diseases, and recent studies suggest that chronic alcoholism is linked to gut microbiome dysbiosis. Here, we investigated the effects of moderate levels of alcohol consumption on the gut microbiome in both rats and humans. The gut microbiota of rats voluntarily consuming a 20 percent ethanol solution, on alternate days, were compared with a non-exposed control group to identify differential taxonomic and functional profiles. Gut microbial diversity profiles were determined using culture-independent amplification, next-generation sequencing and bioinformatic analysis of bacterial 16S ribosomal RNA gene sequence libraries. Our results showed that, compared with controls, ethanol-consuming rats experienced a significant decline in the biodiversity of their gut microbiomes, a state generally associated with dysbiosis. We also observed significant shifts in the overall diversity of the gut microbial communities and a dramatic change in the relative abundance of particular microbes, such as the Lactobacilli. We also compared our results to human fecal microbiome data collected as part of the citizen science American Gut Project. In contrast to the rat data, human drinkers had significantly higher gut microbial biodiversity than non-drinkers. However, we also observed that microbes that differed among the human subjects displayed similar trends in the rat model, including bacteria implicated in metabolic disease.

Many alcohol‐induced health complications are directly attributable to the toxicity of alcohol or its metabolites, but another potential health impact of alcohol may be on the microbial communities of the human gut. Clear distinctions between healthy and diseased‐state gut microbiota have been observed in subjects with metabolic diseases and recent studies suggest that chronic alcoholism is linked to gut microbiome dysbiosis. Here, we investigated the effects of alcohol consumption on the gut microbiome in both rats and humans. The gut microbiota of rats voluntarily consuming a 20% ethanol solution, on alternate days, were compared to a non‐exposed control group to identify differential taxonomic and functional profiles. Gut microbial diversity profiles were determined using culture‐independent amplification, next‐generation sequencing and bioinformatic analysis of bacterial 16S ribosomal RNA gene sequence libraries. Our results showed that, compared to controls, ethanol‐consuming rats experienced a significant decline in the biodiversity of their gut microbiomes, a state generally associated with dysbiosis. We also observed significant shifts in the overall diversity of the gut microbial communities and a dramatic change in the relative abundance of particular microbes, such as the Lactobacilli. We also compared our results to human fecal microbiome data collected as part of the citizen science American Gut Project. In contrast to the rat data, human drinkers had significantly higher gut microbial biodiversity than non‐drinkers. However, we also observed that microbes that differed among the human subjects displayed similar trends in the rat model, including the Lactobacilli as well as bacteria implicated in metabolic disease.Support or Funding InformationNIH AA023291This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Evolutionary analysis combined with ancestral sequence reconstruction (ASR) was utilized to calculate the taxonomic relationship between poly(hydroxybutyrate) depolymerase (PHBase) enzymes belonging to the halophilic genus Halomonas. Enzymes cluster into four distinct clades that differ in sequence length and composition. Like many of the previously studied PHBase proteins, there is a high degree of heterogeneity at the genus level. Ancestor sequences were calculated for each tree node using a maximum likelihood approach. The most ancestral sequence and one extant enzyme from each of the clades were expressed in Escherichia coli, purified to homogeneity, and characterized. The ancestral enzyme binds substrate more efficiently, is kinetically faster, and is more stable at elevated temperatures compared to the extant enzymes. Hence, an evolutionary phylogenetic approach is a viable alternative to other techniques for identifying optimized enzymes for industrial PHB degradation.

Desmosomes are cell-cell junctions present in the epithelia and heart and provide mechanical resistance to these tissues in adults. Thus, it is of no surprise that people born with defects in desmosomal proteins can have numerous defects affecting the skin, hair, and heart. However, unlike other junctional complexes, the role of the desmosomes in epidermal development has largely been unexplored. Therefore, this work fills a major knowledge gap by probing the function and regulation of a critical desmosomal protein, desmoplakin (Dsp) during the development of the Xenopus epidermis. Using morpholinos and CRISPR/ Cas9, we demonstrate that Dsp is required for proper epidermal morphogenesis and mechanical resistance in the embryo. These embryos also display defects in keratin organization and development of ectodermally-derived structures such as the mouth, eye and fin. Importantly, Dsp is required for radial intercalation, a morphogenetic process where basally-located cells move into the outer epidermal layer. Decrease in Dsp results in "halted" radial intercalation, affecting the development of small secretory cells and multiciliated cells. Finally, this study highlights a role for c-Jun N-terminal Kinase (JNK) in regulating desmosome dynamics in the epidermis of the developing embryo. In this study, we use a tractable in vivo system to demonstrate that desmosomes perturb epidermal morphogenesis and uncover a novel role for desmosomes in radial intercalation.