Investigating the Knowledge of Prebiotics, Probiotics, and Synbiotics That May Help to Improve the Gut-Organ Axis Function in Middle-Aged and Older Adults.

BACKGROUND AND AIMS: The use of gut biotics, including probiotics, prebiotics, and synbiotics, has shown substantial potential in the management of various health conditions possibly through the gut-organ axis. The role of gut biotics in modulating the gut-brain axis is becoming evident with more research focusing on this intervention. Improvement of gut-organ axis function is possible by using food-related products called gut biotics. However, there is limited comprehension of the knowledge and use of these intestinal or gut biotics. Our aim was to recognize knowledge gaps and assess the improvement of understanding following an education intervention. METHODS: A single-arm study encompassing a convenient sample of 161 inpatient and outpatient subjects aged 50 years and older was conducted at the University of Alberta Hospital from June to August 2023. Knowledge about gut biotics was evaluated using a structured questionnaire consisting of 16 questions and involving six thematic areas. To ensure validity, the questionnaire was pre-tested on 10 physicians and residents who were not part of the study. The questionnaire was administered to study subjects prior to receiving an information sheet about gut biotics. Two weeks after receiving the information sheet, all participants were contacted by phone, and the same questionnaire was administered again. Of the 161 patients, 122 completed the pre-intervention and post-intervention questionnaires and were considered in the analysis. RESULTS: The mean age of the participants was 72 years (SD: 10.8), 57% comprised women, and 39% had less than a high school education. The proportion of polypharmacy and multimorbidity was 87% and 97%, respectively. Following the intervention, there was a noticeable enhancement in knowledge across all the themes, with statistical significance (p<0.001) observed in 14 out of 16 questions as determined by the homogeneity statistical test. CONCLUSIONS: Knowledge gaps in gut biotics were prevalent among study participants, and the educational intervention effectively contributed to the enhancement of knowledge. The results of this study provide valuable information for the development of targeted health education strategies focusing on gut biotics, which may play a role in improving gut-organ axis function.

Approach to the diagnosis and management of dysbiosis.

All microorganisms like bacteria, viruses and fungi that reside within a host environment are considered a microbiome. The number of bacteria almost equal that of human cells, however, the genome of these bacteria may be almost 100 times larger than the human genome. Every aspect of the physiology and health can be influenced by the microbiome living in various parts of our body. Any imbalance in the microbiome composition or function is seen as dysbiosis. Different types of dysbiosis are seen and the corresponding symptoms depend on the site of microbial imbalance. The contribution of the intestinal and extra-intestinal microbiota to influence systemic activities is through interplay between different axes. Whole body dysbiosis is a complex process involving gut microbiome and non-gut related microbiome. It is still at the stage of infancy and has not yet been fully understood. Dysbiosis can be influenced by genetic factors, lifestyle habits, diet including ultra-processed foods and food additives, as well as medications. Dysbiosis has been associated with many systemic diseases and cannot be diagnosed through standard blood tests or investigations. Microbiota derived metabolites can be analyzed and can be useful in the management of dysbiosis. Whole body dysbiosis can be addressed by altering lifestyle factors, proper diet and microbial modulation. The effect of these interventions in humans depends on the beneficial microbiome alteration mostly based on animal studies with evolving evidence from human studies. There is tremendous potential for the human microbiome in the diagnosis, treatment, and prognosis of diseases, as well as, for the monitoring of health and disease in humans. Whole body system-based approach to the diagnosis of dysbiosis is better than a pure taxonomic approach. Whole body dysbiosis could be a new therapeutic target in the management of various health conditions.

Microbial Therapeutics in Neurocognitive and Psychiatric Disorders.

Microbial therapeutics, which include gut biotics and fecal transplantation, are interventions designed to improve the gut microbiome. Gut biotics can be considered as the administration of direct microbial populations. The delivery of this can be done through live microbial flora, certain food like fiber, microbial products (metabolites and elements) obtained through the fermentation of food products, or as genetically engineered substances, that may have therapeutic benefit on different health disorders. Dietary intervention and pharmacological supplements with gut biotics aim at correcting disruption of the gut microbiota by repopulating with beneficial microorganism leading to decrease in gut permeability, inflammation, and alteration in metabolic activities, through a variety of mechanisms of action. Our understanding of the pharmacokinetics of microbial therapeutics has improved with in vitro models, sampling techniques in the gut, and tools for the reliable identification of gut biotics. Evidence from human studies points out that prebiotics, probiotics and synbiotics have the potential for treating and preventing mental health disorders, whereas with paraprobiotics, proteobiotics and postbiotics, the research is limited at this point. Some animal studies point out that gut biotics can be used with conventional treatments for a synergistic effect on mental health disorders. If future research shows that there is a possibility of synergistic effect of psychotropic medications with gut biotics, then a gut biotic or nutritional prescription can be given along with psychotropics. Even though the overall safety of gut biotics seems to be good, caution is needed to watch for any known and unknown side effects as well as the need for risk benefit analysis with certain vulnerable populations. Future research is needed before wide spread use of natural and genetically engineered gut biotics. Regulatory framework for gut biotics needs to be optimized. Holistic understanding of gut dysbiosis, along with life style factors, by health care providers is necessary for the better management of these conditions. In conclusion, microbial therapeutics are a new psychotherapeutic approach which offer some hope in certain conditions like dementia and depression. Future of microbial therapeutics will be driven by well-done randomized controlled trials and longitudinal research, as well as by replication studies in human subjects.

Holistic perspective of the role of gut microbes in diabetes mellitus and its management.

The gut microbiota (GM) plays a role in the development and progression of type 1 and type 2 diabetes mellitus (DM) and its complications. Gut dysbiosis contributes to the pathogenesis of DM. The GM has been shown to influence the efficacy of different antidiabetic medications. Intake of gut biotics, like prebiotics, probiotics and synbiotics, can improve the glucose control as well as the metabolic profile associated with DM. There is some preliminary evidence that it might even help with the cardiovascular, ophthalmic, nervous, and renal complications of DM and even contribute to the prevention of DM. More large-scale research studies are needed before wide spread use of gut biotics in clinical practice as an adjuvant therapy to the current management of DM.

Gut microbes in neurocognitive and mental health disorders.

INTRODUCTION: As individuals age, the prevalence of neurocognitive and mental health disorders increases. Current biomedical treatments do not completely address the management of these conditions. Despite new pharmacological therapy the challenges of managing these diseases remain.There is increasing evidence that the Gut Microbiome (GM) and microbial dysbiosis contribute to some of the more prevalent mental health and neurocognitive disorders, such as depression, anxiety, obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), schizophrenia, bipolar disorder (BP), and dementia as well as the behavioural and psychological symptoms of dementia (BPSD) through the microbiota-gut-brain axis. Methodology: Scoping review about the effect of gut microbiota on neurocognitive and mental health disorders. RESULTS: This scoping review found there is an evolving evidence of the involvement of the gut microbiota in the pathophysiology of neurocognitive and mental health disorders. This manuscript also discusses how the psychotropics used to treat these conditions may have an antimicrobial effect on GM, and the potential for new strategies of management with probiotics and faecal transplantation. CONCLUSIONS: This understanding can open up the need for a gut related approach in these disorders as well as unlock the door for the role of gut related microbiota management. KEY MESSAGES Challenges of managing mental health conditions remain in spite of new pharmacological therapy. Gut dysbiosis is seen in various mental health conditions. Various psychotropic medications can have an influence on the gut microbiota by their antimicrobial effect.

Secreted Phosphatase and Deoxyribonuclease Are Required by Pseudomonas aeruginosa To Defend against Neutrophil Extracellular Traps.

Neutrophil extracellular traps (NETs) are produced by neutrophils as an innate immune defense mechanism to trap and kill microbial pathogens. NETs are comprised of ejected chromatin that forms a lattice structure enmeshed with numerous antimicrobial proteins. In addition to forming the structural backbone of NETs, extracellular DNA (eDNA) has membrane-disrupting antimicrobial activity that contributes to NET killing. Many pathogens produce secreted extracellular DNases to evade the antimicrobial activity of NETs. Pseudomonas aeruginosa encodes an operon of two secreted enzymes, a predicted alkaline phosphatase and a DNase. The DNase (eddB) degrades eDNA to use as a nutrient source. Here we report that both eDNA and NETs are potent inducers of this DNase-phosphatase operon. Furthermore, the secreted DNase contributes to degrading NET DNA and defends P. aeruginosa against NET-mediated killing. We demonstrate that EddA has both alkaline phosphatase and phosphodiesterase (PDase) activities and also protects against the antimicrobial activity of NETs. Although the phosphatase does not cause DNA degradation similar to that of the DNase, its protective function is likely a result of removing the cation-chelating phosphates from the eDNA phosphodiester backbone. Therefore, both the DNase and PDase contribute to defense against NET killing of P. aeruginosa, highlighting the role of DNA-manipulating enzymes in targeting the eDNA in neutrophil extracellular traps.

DNA is an antimicrobial component of neutrophil extracellular traps.

Neutrophil extracellular traps (NETs) comprise an ejected lattice of chromatin enmeshed with granular and nuclear proteins that are capable of capturing and killing microbial invaders. Although widely employed to combat infection, the antimicrobial mechanism of NETs remains enigmatic. Efforts to elucidate the bactericidal component of NETs have focused on the role of NET-bound proteins including histones, calprotectin and cathepsin G protease; however, exogenous and microbial derived deoxyribonuclease (DNase) remains the most potent inhibitor of NET function. DNA possesses a rapid bactericidal activity due to its ability to sequester surface bound cations, disrupt membrane integrity and lyse bacterial cells. Here we demonstrate that direct contact and the phosphodiester backbone are required for the cation chelating, antimicrobial property of DNA. By treating NETs with excess cations or phosphatase enzyme, the antimicrobial activity of NETs is neutralized, but NET structure, including the localization and function of NET-bound proteins, is maintained. Using intravital microscopy, we visualized NET-like structures in the skin of a mouse during infection with Pseudomonas aeruginosa. Relative to other bacteria, P. aeruginosa is a weak inducer of NETosis and is more resistant to NETs. During NET exposure, we demonstrate that P. aeruginosa responds by inducing the expression of surface modifications to defend against DNA-induced membrane destabilization and NET-mediated killing. Further, we show induction of this bacterial response to NETs is largely due to the bacterial detection of DNA. Therefore, we conclude that the DNA backbone contributes both to the antibacterial nature of NETs and as a signal perceived by microbes to elicit host-resistance strategies.