Intestinal transgene delivery with native E. coli chassis allows persistent physiological changes.

Live bacterial therapeutics (LBTs) could reverse diseases by engrafting in the gut and providing persistent beneficial functions in the host. However, attempts to functionally manipulate the gut microbiome of conventionally raised (CR) hosts have been unsuccessful because engineered microbial organisms (i.e.

Diet and feeding pattern modulate diurnal dynamics of the ileal microbiome and transcriptome.

Compositional oscillations of the gut microbiome are essential for normal peripheral circadian rhythms, both of which are disrupted in diet-induced obesity (DIO). Although time-restricted feeding (TRF) maintains circadian synchrony and protects against DIO, its impact on the dynamics of the cecal gut microbiome is modest. Thus, other regions of the gut, particularly the ileum, the nexus for incretin and bile acid signaling, may play an important role in entraining peripheral circadian rhythms.

Intermittent Hypoxia and Hypercapnia Alter Diurnal Rhythms of Luminal Gut Microbiome and Metabolome.

Obstructive sleep apnea (OSA), characterized by intermittent hypoxia and hypercapnia (IHC), affects the composition of the gut microbiome and metabolome. The gut microbiome has diurnal oscillations that play a crucial role in regulating circadian and overall metabolic homeostasis. Thus, we hypothesized that IHC adversely alters the gut luminal dynamics of key microbial families and metabolites.

Obesity and Insulin Resistance Promote Atherosclerosis through an IFNγ-Regulated Macrophage Protein Network.

Type 2 diabetes (T2D) is associated with increased risk for atherosclerosis; however, the mechanisms underlying this relationship are poorly understood. Macrophages, which are activated in T2D and causatively linked to atherogenesis, are an attractive mechanistic link. Here, we use proteomics to show that diet-induced obesity and insulin resistance (obesity/IR) modulate a pro-atherogenic "macrophage-sterol-responsive-network" (MSRN), which, in turn, predisposes macrophages to cholesterol accumulation.