Bacteria in the gastrointestinal tract produce amino acid bile acid amidates that can affect host-mediated metabolic processes^1–6; however, the bacterial gene(s) responsible for their production remain unknown. Herein, we report that bile salt hydrolase (BSH) possesses dual functions in bile acid metabolism. Specifically, we identified a previously unknown role for BSH as an amine N-acyltransferase that conjugates amines to bile acids, thus forming bacterial bile acid amidates (BBAAs). To characterize this amine N-acyltransferase BSH activity, we used pharmacological inhibition of BSH, heterologous expression of bsh and mutants in Escherichia coli and bsh knockout and complementation in Bacteroides fragilis to demonstrate that BSH generates BBAAs. We further show in a human infant cohort that BBAA production is positively correlated with the colonization of bsh-expressing bacteria. Lastly, we report that in cell culture models, BBAAs activate host ligand-activated transcription factors including the pregnane X receptor and the aryl hydrocarbon receptor. These findings enhance our understanding of how gut bacteria, through the promiscuous actions of BSH, have a significant role in regulating the bile acid metabolic network.

Oat is among the food crops and ancient grains cultivated and consumed worldwide. It is gaining in popularity owing to its nutritional composition and multifunctional benefits of select bioactive compounds. Beta-glucan is an important component of dietary fiber found in oat grains. It is the major active compound in oats with proven cholesterol-lowering and antidiabetic effects. Oats also provide substantial levels of other bioactive compounds such as phenolic acids, tocols, sterols, avenacosides, and avenanthramides. The consumption of oats has been determined to be beneficial for human health by promoting immunomodulation and improving gut microbiota. In addition, oat consumption assists in preventing diseases such as atherosclerosis, dermatitis, and some forms of cancer. While much has been published in relation to oat nutrients and oat fibers and their impact on major diseases, the oat industries and consumers may benefit from greater knowledge and understanding of clinical effects, range of occurrence, distribution, therapeutic doses and food functional attributes of other oat bioactives such as avenanthramides and saponins as well as other anti-inflammatory agents found in the cereal. This review focuses on the various studies relevant to the contribution of the consumption of oats and oat-based products in preventing human diseases and promoting human health.

Global food security is a worldwide concern. Food insecurity is a significant threat to poverty and hunger eradication goals. Agriculture is one of the focal points in the global policy agenda. Increases in agricultural productivity through the incorporation of technological advances or expansion of cultivable land areas have been pushed forward. However, production growth has slowed in many parts of the world due to various endemic challenges, such as decreased investment in agricultural research, lack of infrastructure in rural areas, and increasing water scarcity. Climate change adversities in agriculture and food security are increasing. Recently, the COVID-19 pandemic has severely affected global food supply chains. Economic and social instability from the pandemic contribute to long-term disturbances. Additionally, conflicts such as war directly affect agriculture by environmental degradation, violence, and breaches of national and international trade agreements. A combination of food security and climate change challenges along with increased conflicts among nations and post-COVID-19 social and economic issues bring bigger and more serious threats to agriculture. This necessitates the strategic design of policies through multifaceted fields regarding food systems. In this comprehensive review, we explore how these three challenging factors, COVID-19, climate change, and conflicts, are interrelated, and how they affect food security. We discuss the impact of these issues on the agricultural sector, plus possible ways of preventing or overcoming such adverse effects.

Atherosclerosis and resulting cardiovascular disease are the leading causes of death in the US. Hyperhomocysteinemia (HHcy), or the accumulation of the intermediate amino acid homocysteine, is an independent risk factor for atherosclerosis, but the intricate biological processes mediating this effect remain elusive. Several factors regulate homocysteine levels, including the activity of several enzymes and adequate levels of their coenzymes, including pyridoxal phosphate (vitamin B6), folate (vitamin B9), and methylcobalamin (vitamin B12). To better understand the biological influence of HHcy on the development and progression of atherosclerosis, apolipoprotein-E-deficient (apoE^−/− mice), a model for human atherosclerosis, were fed a hyperhomocysteinemic diet (low in methyl donors and B vitamins) (HHD) or a control diet (CD). After eight weeks, the plasma, aorta, and liver were collected to quantify methylation metabolites, while plasma was also used for a broad targeted metabolomic analysis. Aortic plaque burden in the brachiocephalic artery (BCA) was quantified via 14T magnetic resonance imaging (MRI). A severe accumulation of plasma and hepatic homocysteine and an increased BCA plaque burden were observed, thus confirming the atherogenic effect of the HHD. Moreover, a decreased methylation capacity in the plasma and aorta, indirectly assessed by the ratio of S-adenosylmethionine to S-adenosylhomocysteine (SAM:SAH) was detected in HHD mice together with a 172-fold increase in aortic cystathionine levels, indicating increased flux through the transsulfuration pathway. Betaine and its metabolic precursor, choline, were significantly decreased in the livers of HHD mice versus CD mice. Widespread changes in the plasma metabolome of HHD mice versus CD animals were detected, including alterations in acylcarnitines, amino acids, bile acids, ceramides, sphingomyelins, triacylglycerol levels, and several indicators of dysfunctional lipid metabolism. This study confirms the relevance of severe HHcy in the progression of vascular plaque and suggests novel metabolic pathways implicated in the pathophysiology of atherosclerosis.

Diet quality during early life may influence neurodevelopmental trajectories, but the associations between ultra-processed food (UPF) intake and neurocognitive outcomes has not been broadly examined. To examine whether cumulative UPF intake from infancy through early childhood is associated with cognitive performance at 24 and 72 months and with subcortical brain volumes at 72 months. In this prospective birth cohort study, multiple 24-hour dietary assessments were used to calculate the percentage of UPF-calorie intake, using the Nova classification system. Cumulative UPF intake from 6 to 24 and from 6 to 72 months was summarized as the area under the curve. Cognitive performance was assessed at 24 and 72 months, and subcortical brain volumes were derived from T1-weighted MRI scans at 72 months. Associations were examined using multiple univariate linear regressions with false discovery rate (FDR) correction. Cumulative UPF intake was not associated with cognitive performance at either 24 months (n=144, 57% girls) or 72 months (n=93, 59% girls). In contrast, cumulative UPF intake from 6 to 72 months (n=79, 58% girls) was inversely associated with the volumes of the bilateral accumbens, left amygdala, bilateral pallidum, left putamen, and bilateral thalamus (all FDR-adjusted p < 0.05). On average, a 10% higher proportion of cumulative UPF intake was associated with a 1.92% lower subcortical volume (CI95% -3.29, -0.58). Associations were consistent across exposure windows (6-24 months compared with 72 months) and UPF subtypes (e.g., snacks, fast food). Greater cumulative UPF intake from infancy through early childhood was associated with differences in neurodevelopment at age six years. These findings highlight this period as a potentially relevant window for nutrition-focused prevention efforts. Future studies are needed to clarify specific windows, neurobiological mechanisms, identify specific nutritional factors, and define long-term implications.