Feeding with Sustainably Sourdough Bread Has the Potential to Promote the Healthy Microbiota Metabolism at the Colon Level

Knowledge on environmental factors, which may compose the gut microbiota, and drive the host physiology and health is of paramount importance. Human dietary habits and food compositions are pivotal drivers to assembly the human gut microbiota, but, inevitably, unmapped for many diet components, which are poorly investigated individually.

Intestinal Transgene Delivery with Native E. coli Chassis Allows Persistent Physiological Changes

Live bacterial therapeutics (LBT) could reverse disease 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., chassis) cannot colonize the hostile luminal environment. In this proof-of-concept study, we use native bacteria as chassis for transgene delivery to impact CR host physiology. Native Escherichia coli isolated from stool cultures of CR mice were modified to express functional bacterial (bile salt hydrolase) and eukaryotic (Interleukin-10) genes. Reintroduction of these strains induces perpetual engraftment in the intestine. In addition, engineered native E. coli can induce functional changes that affect host physiology and reverse pathology in CR hosts months after administration. Thus, using native bacteria as chassis to knock-in specific functions allows mechanistic studies of specific microbial activities in the microbiome of CR hosts, and enables LBT with curative intent.

Controlled Complexity: Optimized Systems to Study the Role of the Gut Microbiome in Host Physiology

The profound impact of the gut microbiome on host health has led to a revolution in biomedical research, motivating researchers from disparate fields to define the specific molecular mechanisms that mediate host-beneficial effects. The advent of genomic technologies allied to the use of model microbiomes in gnotobiotic mouse models has transformed our understanding of intestinal microbial ecology and the impact of the microbiome on the host. However, despite incredible advances, our understanding of the host-microbiome dialogue that shapes host physiology is still in its infancy. Progress has been limited by challenges associated with developing model systems that are both tractable enough to provide key mechanistic insights while also reflecting the enormous complexity of the gut ecosystem. Simplified model microbiomes have facilitated detailed interrogation of transcriptional and metabolic functions of the microbiome but do not recapitulate the interactions seen in complex communities. Conversely, intact complex communities from mice or humans provide a more physiologically relevant community type, but can limit our ability to uncover high-resolution insights into microbiome function. Moreover, complex microbiomes from lab-derived mice or humans often do not readily imprint human-like phenotypes. Therefore, improved model microbiomes that are highly defined and tractable, but that more accurately recapitulate human microbiome-induced phenotypic variation are required to improve understanding of fundamental processes governing host-microbiome mutualism. This improved understanding will enhance the translational relevance of studies that address how the microbiome promotes host health and influences disease states. Microbial exposures in wild mice, both symbiotic and infectious in nature, have recently been established to more readily recapitulate human-like phenotypes. The development of synthetic model communities from such “wild mice” therefore represents an attractive strategy to overcome the limitations of current approaches. Advances in microbial culturing approaches that allow for the generation of large and diverse libraries of isolates, coupled to ever more affordable large-scale genomic sequencing, mean that we are now ideally positioned to develop such systems. Furthermore, the development of sophisticated in vitro systems is allowing for detailed insights into host-microbiome interactions to be obtained. Here we discuss the need to leverage such approaches and highlight key challenges that remain to be addressed.

Microbe defines the efficacy of chemotherapeutic drug: a complete paradigm

ABSTRACT The human body harbors a diverse microbiome that regulates host physiology and disease development. Several studies have also been reported where the human microbiome interferes with the efficacy of chemotherapeutics. Reports have also suggested the use of microbes in specific targeting and drug delivery. This review mainly focuses on the alteration in the efficacy of the drug by human microbiota. We have also discussed how the diversity in microbes can determine the therapeutic outcomes of a particular drug. The pathways involved in the alteration are also focused, with some highlights on microbes being used in cancer therapy.

Modelling the Effects of Traits and Abiotic Factors on Viral Lysis in Phytoplankton

A mechanistic system dynamics description is developed of the interactions between a single lytic-virus – phytoplankton-host couple. The model has state variables for virus, uninfected and infected host biomass, and describes virus and host allometry and physiology. The model, analogous to experimental laboratory virus-host systems but more amenable to hypothesis testing, enables us to explore the relative importance of some of the poorly understood factors suspected to impact plankton virus-host dynamics. Model behaviour is explored with respect to abiotic factors (light, mixed layer depth, nutrient and suspended particle loading), host traits (size, growth rate, motility) and virus traits (size, latent period and burst size including linkage to compromised host physiology, and decay rates). Simulations show that the optimal performance of a virus (i.e., optimal trait characterisation) is a function of many factors relating to the virus, its host, and the environment. In general, smaller viruses and smaller motile hosts give rise to more productive infection outcomes that result in rapid demise of the host and high post-infection virus abundance. However, the timing of the development of the interaction (relative abundance of virus to host at the start of rapid host population growth), overlain on the growth rate and physiological status of the host, was seen to be critical. Thus, for any one configuration of the model, the inoculum level of the virus (multiplicity of infection- MOI) displayed an optimum time-point between the infection developing too quickly, limiting biomass accumulation, or too late so that nutrient or light limitation compromised host physiology and hence the burst size. Importantly, the success of an infection depended also upon the suspended particle load which, if high enough, adsorbs so many viruses that the infection does not develop. We conclude that adding viruses to plankton ecosystem models in a realistic fashion is a complicated process due to the way that the individual and coupled virus-host processes interact with the environment.