Immunological Tolerance and Function: Associations Between Intestinal Bacteria, Probiotics, Prebiotics, and Phages

Abstract

Post-birth there is a bacterial assault on all mucosal surfaces. The intestinal microbiome is an important participant in health and disease. The pattern of composition and concentration of the intestinal microbiome varies greatly. Therefore, achieving immunological tolerance in the first 3–4 years of life is critical for maintaining health throughout a lifetime. Probiotic bacteria are organisms that afford beneficial health effects to the host and in certain instances may protect against the development of disease. The potential benefits of modifying the composition of the intestinal microbial cohort for therapeutic benefit is evident in the use in high risks groups such as premature infants, children receiving antibiotics, rotavirus infections in non-vaccinated children and traveler's diarrhea in adults. Probiotics and prebiotics are postulated to have immunomodulating capabilities by influencing the intestinal microbial cohort and dampening the activity of pathobiont intestinal microbes, such as Klebsiella pneumonia and Clostridia perfringens. Lactobacilli and Bifidobacteria are examples of probiotics found in the large intestine and so far, the benefits afforded to probiotics have varied in efficacy. Most likely the efficacy of probiotic bacteria has a multifactorial dependency, namely on a number of factors that include agents used, the dose, the pattern of dosing, and the characteristics of the host and the underlying luminal microbial environment and the activity of bacteriophages. Bacteriophages, are small viruses that infect and lyse intestinal bacteria. As such it can be posited that these viruses display an effective local protective control mechanism for the intestinal barrier against commensal pathobionts that indirectly may assist the host in controlling bacterial concentrations in the gut. A co-operative activity may be envisaged between the intestinal epithelia, mucosal immunity and the activity of bacteriophages to eliminate pathobiots, highlighting the potential role of bacteriophages in assisting with maintaining intestinal homeostasis. Hence bacteriophage local control of inflammation and immune responses may be an additional immunological defense mechanism that exploits bacteriophage–mucin glycoprotein interactions that controls bacterial diversity and abundance in the mucin layers of the gut. Moreover, and importantly the efficacy of probiotics may be dependent on the symbiotic incorporation of prebiotics, and the abundance and diversity of the intestinal microbiome encountered. The virome may be an important factor that determines the efficacy of some probiotic formulations.

Insight into Polyphenol and Gut Microbiota Crosstalk: Are Their Metabolites the Key to Understand Protective Effects against Metabolic Disorders?

“…This is exemplified by the sensitization of methicillin-resistant Staphylococcus aureus to β-lactam through the (−)-epicatechin gallate-mediated alterations of the bacterium cell wall bilayer, and enhanced release of lipotechoic acid from the cytoplasmic membrane [ 126 ]. Polyphenols, acting as prebiotics, have also been shown to modulate gut metabolism and immunity as well as inflammatory pathways through the change of T-cell functions, inhibition of mast cell degranulation, and down regulation of inflammatory cytokine responses [ 127 , 128 , 129 , 130 ]. Studies in animals and in humans have shown modification of colon microflora by polyphenolic compounds, resulting in growth inhibition of certain bacterial groups while permitting others to flourish [ 131 , 132 , 133 ].…”

Microbiome Product Toxicology: Regulatory View on Translational Challenges

“…These genetically modified organisms (GMO) are usually designed to either selectively modify or eliminate members of the patient microbiota. Phage therapies implement bacteriophage (i.e.,bacteria-specific viruses) natural competence to selectively target and kill bacteria and are aimed to be an alternative approach to the use of antibiotics (Paule et al 2018;Divya Ganeshan and Hosseinidoust 2019;Vitetta et al 2018). The sponsor needs to ensure the lack of toxicological effects of LPBs toward the patient both at local and systemic levels, and toward patient's microbiota to ensure a selective and controlled action.…”

“…Gut microbiota are known to play a key role in the maintenance of homeostasis and health (Buret et al 2019;Crespo-Piazuelo et al 2018;Kostic et al 2013;Martín et al 2016;Vitetta et al 2018). Same ascertainments have been made with other epithelium-associated microbiota such as skin (Johnson et al 2018;Muszer et al 2015;Nakamizo et al 2015), oral (Solbiati and Frias-Lopez 2018), and vaginal (Chen et al 2018;Nugeyre et al 2019) microbiota.…”

A New Vision of IgA Nephropathy: The Missing Link

“…Probiotics have anti-inflammatory, anti-oxidative, and other favorable gut-modulating properties [68]. Especially species from the Lactobacilli and Bifidobacteria genera were shown to support the humoral immune responses against environmental toxins and antigens [69]. The use of probiotics or symbiotics in patients with chronic kidney disease has been shown to have some beneficial effects on the uremic toxins, blood urea nitrogen, oxidative stress, and markers of inflammation also by enhancing barrier function [70][71][72][73].…”