Dietary protein source strongly alters gut microbiota composition and function.

The source of protein in a persons diet affects their total life expectancy. However, the mechanisms by which dietary protein sources differentially impact human health and life expectancy are poorly understood. Dietary choices have major impacts on the composition and function of the intestinal microbiota that ultimately mediate host health. This raises the possibility that health outcomes based on dietary protein sources might be driven by interactions between dietary protein and the gut microbiota. In this study, we determine the effects of seven different sources of dietary protein on the gut microbiota in mice. We apply an integrated metagenomics-metaproteomics approach to simultaneously investigate the effects of these dietary protein sources on the gut microbiotas composition and function. The protein abundances measured by metaproteomics can provide microbial species abundances, and evidence for the phenotype of microbiota members on the molecular level because measured proteins allow us to infer the metabolic and physiological processes used by a microbial community. We showed that dietary protein source significantly altered the species composition and overall function of the gut microbiota. Different dietary protein sources led to changes in the abundance of microbial amino acid degrading proteins and proteins involved in the degradation of glycosylations on dietary protein. In particular, brown rice and egg white protein increased the abundance of amino acid degrading enzymes and egg white protein increased the abundance of bacteria and proteins usually associated with the degradation of the intestinal mucus barrier. These results show that dietary protein source can change the gut microbiotas metabolism, which could have major implications in the context of gut microbiota mediated diseases.

Clusterin ameliorates tau pathology in vivo by inhibiting fibril formation.

The molecular chaperone Clusterin (CLU) impacts the amyloid pathway in Alzheimer's disease (AD) but its role in tau pathology is unknown. We observed CLU co-localization with tau aggregates in AD and primary tauopathies and CLU levels were upregulated in response to tau accumulation. To further elucidate the effect of CLU on tau pathology, we utilized a gene delivery approach in CLU knock-out (CLU KO) mice to drive expression of tau bearing the P301L mutation. We found that loss of CLU was associated with exacerbated tau pathology and anxiety-like behaviors in our mouse model of tauopathy. Additionally, we found that CLU dramatically inhibited tau fibrilization using an in vitro assay. Together, these results demonstrate that CLU plays a major role in both amyloid and tau pathologies in AD.

Life-extending dietary restriction and ovariectomy each increase leucine oxidation and alter leucine allocation in grasshoppers.

Reduced reproduction and dietary restriction each extend lifespan in many animal models, but possible contributions of nutrient oxidation and allocation are largely unknown. Ovariectomy and eating 70% of ad libitum-feeding each extend lifespan in lubber grasshoppers. When feeding levels between the two groups are matched, ovariectomy increases fat and protein storage while dietary restriction reduces fat storage. Because of these disparities in nutrient investment, metabolism may differ between these two life-extending treatments. Therefore, we examined the allocation and organismal oxidation of one representative of each macronutrient class: leucine, oleic acid, and glucose. Ovariectomy and dietary restriction each increased oxidation of dietary leucine. Dietary leucine may play a special role in aging because amino acids stimulate cellular growth. Speeding oxidation of leucine may attenuate cellular growth. Allocation of leucine to muscle was the clearest difference between ovariectomy and dietary restriction in this study. Ovariectomy reduced allocation of leucine to femur muscle, whereas dietary restriction increased allocation of leucine to femur muscle. This allocation likely corresponds to muscle maintenance for locomotion, suggesting dietary restriction increases support for locomotion, perhaps to search for food. Last, ovariectomy decreased oxidation of dietary oleic acid and glucose, perhaps to save them for storage, but the site of storage is unclear. This study suggests that the oxidation of branched-chain amino acids may be an underappreciated mechanism underlying lifespan extension.