Parkinson’s disease (PD) is a neurodegenerative disease that is generally thought to be caused by multiple factors, including environmental and genetic factors. Emerging evidence suggests that intestinal disturbances, such as constipation, are common non-motor symptoms of PD. Gut inflammation may be closely associated with pathogenesis in PD. This review aims to discuss the cross-talk between gut inflammation and PD pathology initiation and progression. Firstly, we will highlight the studies demonstrating how gut inflammation is related to PD. Secondly, we will analyze how gut inflammation spreads from the gastro-intestine to the brain. Here, we will mainly discuss the neural pathway of pathologic α-syn and the systemic inflammatory routes. Thereafter, we will address how alterations in the brain subsequently lead to dopaminergic neuron degeneration, in which oxidative stress, glutamate excitotoxicity, T cell driven inflammation and cyclooxygenase-2 (COX-2) are involved. We conclude a model of PD triggered by gut inflammation, which provides a new angle to understand the mechanisms of the disease.

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Gut Inflammation in Association With Pathogenesis of Parkinson's Disease.

Background The inflammatory bowel diseases, Crohn's disease and ulcerative colitis are related multifactorial diseases. Their pathogenesis is influenced by each individual's immune system, the environmental factors within exposome and genetic predisposition. Smoking habit is the single best-established environmental factor that influences disease phenotype, behaviour and response to therapy. Aim To assess current epidemiological, experimental and clinical evidence that may explain how smoking impacts on the pathogenesis of inflammatory bowel disease. Methods A Medline search for 'cigarette smoking', in combination with terms including 'passive', 'second-hand', 'intestinal inflammation', 'Crohn's disease', 'ulcerative colitis', 'colitis'; 'intestinal epithelium', 'immune system', 'intestinal microbiota', 'tight junctions', 'mucus', 'goblet cells', 'Paneth cells', 'autophagy'; 'epigenetics', 'genes', 'DNA methylation', 'histones', 'short noncoding/long noncoding RNAs'; 'carbon monoxide/CO' and 'nitric oxide/NO' was performed. Results Studies found evidence of direct and indirect effects of smoking on various parameters, including oxidative damage, impairment of intestinal barrier and immune cell function, epigenetic and microbiota composition changes, that contribute to the pathogenesis of inflammatory bowel disease. Conclusions Cigarette smoking promotes intestinal inflammation by affecting the function and interactions among intestinal epithelium, immune system and microbiota/microbiome.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/apt.15774

Review article: impact of cigarette smoking on intestinal inflammation-direct and indirect mechanisms.

Nature is full of examples of symbiotic relationships. The critical symbiotic relation between host and mutualistic bacteria is attracting increasing attention to the degree that the gut microbiome is proposed by some as a new organ system. The microbiome exerts its systemic effect through a diverse range of metabolites, which include gaseous molecules such as H2, CO2, NH3, CH4, NO, H2S, and CO. In turn, the human host can influence the microbiome through these gaseous molecules as well in a reciprocal manner. Among these gaseous molecules, NO, H2S, and CO occupy a special place because of their widely known physiological functions in the host and their overlap and similarity in both targets and functions. The roles that NO and H2S play have been extensively examined by others. Herein, the roles of CO in host-gut microbiome communication are examined through a discussion of (1) host production and function of CO, (2) available CO donors as research tools, (3) CO production from diet and bacterial sources, (4) effect of CO on bacteria including CO sensing, and (5) gut microbiome production of CO. There is a large amount of literature suggesting the "messenger" role of CO in host-gut microbiome communication. However, much more work is needed to begin achieving a systematic understanding of this issue.

Hadas Zamir

Papers

Cigarette smoking associates inversely with a cluster of two autoimmune diseases: ulcerative colitis and pemphigus.