Modulation of Gut Microbiota and Immune System by Probiotics, Pre-biotics, and Post-biotics

The human gastrointestinal tract harbours a complex microbial community, which interacts with the mucosal immune system closely. Gut microbiota plays a significant role in maintaining host health, which could supply various nutrients, regulate energy balance, modulate the immune response, and defence against pathogens. Therefore, maintaining a favourable equilibrium of gut microbiota through modulating bacteria composition, diversity, and their activity is beneficial to host health. Several studies have shown that probiotics and pre-biotics could directly and indirectly regulate microbiota and immune response. In addition, post-biotics, such as the bioactive metabolites, produced by gut microbiota, and/or cell-wall components released by probiotics, also have been shown to inhibit pathogen growth, maintain microbiota balance, and regulate an immune response. This review summarises the studies concerning the impact of probiotics, pre-biotics, and post-biotics on gut microbiota and immune systems and also describes the underlying mechanisms of beneficial effects of these substances. Finally, the future and challenges of probiotics, pre-biotics, and post-biotics are proposed.

Current State of Carbohydrate Recognition and C-Type Lectin Receptors in Pneumocystis Innate Immunity

Pneumocystis jirovecii is one of the most common fungal pathogens in immunocompromised individuals. Pneumocystis jirovecii pneumonia (PJP) causes a significant host immune response that is driven greatly by the organism’s cell wall components including β-glucans and major surface glycoprotein (Msg). These ligands interact with a number of C-type lectin receptors (CLRs) leading to downstream activation of proinflammatory signaling pathways. This minireview provides a brief overview summarizing known CLR/Pneumocystis interactions.

Development of a Hypoxia-Activated Trehalose Diester for the Treatment of Solid Tumours

<p><b>The potential of bacterial cell wall components in the treatment of various cancers was initially realised in the late 1800s during pioneering work with Coley’s toxins. Since this preliminary work, efforts have been concentrated on the isolation and identification of bacterial components that lead to tumour regression. Trehalose dimycolates (TDMs) are compounds isolated from the M. tuberculosis cell wall and are known to activate macrophages to give a polarised Th1 immune response resulting in reduced tumour burden. Consequently, TDMs have shown great promise in the treatment of solid tumours.</b></p> <p>In this thesis, work is presented towards the synthesis of trehalose glycolipid prodrugs that will be specifically activated inside the hypoxic tumour microenvironment, and thereby lead to a more selective form of cancer therapy. These hypoxia-activated trehalose glycolipids incorporate a nitroimidazole trigger that fragments upon enzymatic reduction (in the absence of oxygen) to give the active glycolipid. Throughout the course of this work, it was determined that the nitroimidazole trigger group could not be directly attached to the glycolipid and thus, an alternative carbonate-linker strategy was explored through the use of a reporter fluoroprobe. The validity of this approach was determined in various enzyme and cell-based assays.</p>

Development of a Hypoxia-Activated Trehalose Diester for the Treatment of Solid Tumours

<p><b>The potential of bacterial cell wall components in the treatment of various cancers was initially realised in the late 1800s during pioneering work with Coley’s toxins. Since this preliminary work, efforts have been concentrated on the isolation and identification of bacterial components that lead to tumour regression. Trehalose dimycolates (TDMs) are compounds isolated from the M. tuberculosis cell wall and are known to activate macrophages to give a polarised Th1 immune response resulting in reduced tumour burden. Consequently, TDMs have shown great promise in the treatment of solid tumours.</b></p> <p>In this thesis, work is presented towards the synthesis of trehalose glycolipid prodrugs that will be specifically activated inside the hypoxic tumour microenvironment, and thereby lead to a more selective form of cancer therapy. These hypoxia-activated trehalose glycolipids incorporate a nitroimidazole trigger that fragments upon enzymatic reduction (in the absence of oxygen) to give the active glycolipid. Throughout the course of this work, it was determined that the nitroimidazole trigger group could not be directly attached to the glycolipid and thus, an alternative carbonate-linker strategy was explored through the use of a reporter fluoroprobe. The validity of this approach was determined in various enzyme and cell-based assays.</p>

Genes Associated with the Flax Plant Type (Oil or Fiber) Identified Based on Genome and Transcriptome Sequencing Data

As a result of the breeding process, there are two main types of flax (Linum usitatissimum L.) plants. Linseed is used for obtaining seeds, while fiber flax is used for fiber production. We aimed to identify the genes associated with the flax plant type, which could be important for the formation of agronomically valuable traits. A search for polymorphisms was performed in genes involved in the biosynthesis of cell wall components, lignans, fatty acids, and ion transport based on genome sequencing data for 191 flax varieties. For 143 of the 424 studied genes (4CL, C3′H, C4H, CAD, CCR, CCoAOMT, COMT, F5H, HCT, PAL, CTL, BGAL, ABC, HMA, DIR, PLR, UGT, TUB, CESA, RGL, FAD, SAD, and ACT families), one or more polymorphisms had a strong correlation with the flax type. Based on the transcriptome sequencing data, we evaluated the expression levels for each flax type-associated gene in a wide range of tissues and suggested genes that are important for the formation of linseed or fiber flax traits. Such genes were probably subjected to the selection press and can determine not only the traits of seeds and stems but also the characteristics of the root system or resistance to stresses at a particular stage of development, which indirectly affects the ability of flax plants to produce seeds or fiber.

Legacy in Cardiovascular Risk Factors Control: From Theory to Future Therapeutic Strategies?

In medicine, a legacy effect is defined as the sustained beneficial effect of a given treatment on disease outcomes, even after cessation of the intervention. Initially described in optimized control of diabetes, it was also observed in clinical trials exploring intensification strategies for other cardiovascular risk factors, such as hypertension or hypercholesterolemia. Mechanisms of legacy were particularly deciphered in diabetes, leading to the concept of metabolic memory. In a more discreet manner, other memory phenomena were also described in preclinical studies that demonstrated long-lasting deleterious effects of lipids or angiotensin II on vascular wall components. Interestingly, epigenetic changes and reactive oxygen species (ROS) appear to be common features of “memory” of the vascular wall.