M3 Lecture 2: Microbiome and Disease PDF

M3 - Lecture 2: Microbiome and disease HSS4102 C: Developmental Origins of Health and Disease Lei Cao Assistant Professor Interdisciplinary School of Health Sciences Faculty of Health Sciences, University of Ottawa ...

M3 - Lecture 2: Microbiome and disease HSS4102 C: Developmental Origins of Health and Disease Lei Cao Assistant Professor Interdisciplinary School of Health Sciences Faculty of Health Sciences, University of Ottawa  Learning outcomes By the end of this lecture you will be able to: Explain the concept of dysbiosis and its association with various conditions and diseases. Describe the gut-brain axis and the systems involved in its function. Analyze the relationship between dysbiosis and obesity. Discuss the role of dysbiosis in gastrointestinal disorders, specifically Irritable Bowel Syndrome (IBS) and Inflammatory Bowel Disease (IBD). Differentiate between probiotics and prebiotics, and explain their respective functions in gut health.  Dysbiosis A condition in which the gut bacteria become imbalanced (beneficial bacteria vs harmful ones). There are many factors that can lead to dysbiosis, including the excessive or wrong use of antibiotics, excessive alcohol consumption, increased intake of sugar or protein, frequent use of antacids, exposure to pesticides, and chronic stress. Poor dental hygiene and anxiety can also lead to dysbiosis. https://www.news-medical.net/health/Dysbiosis-Diagnosis.aspx  Dysbiosis Dysbiosis has been Dysbiosis doesn’t cause associated with these diseases by itself, diseases such but it creates an as Inflammatory Bowel environment that may Disease (IBD), Obesity, worsen these conditions Type 1 and Type 2 or increase susceptibility Diabetes, Autism, and certain gastrointestinal cancers.  Dysbiosis and the gut-brain axis The bidirectional communication between the central nervous system and gut microbiota, referred to as the gut- brain-axis. Through signaling from gut-microbiota to brain and from brain to gut- microbiota by means of neural, endocrine, immune, and humoral links. Hormones, neurotransmitters and immunological factors released from the gut are known to send signals to the brain either directly or via autonomic neurons. Ann Gastroenterol. 2015 Apr-Jun; 28(2): 203–209. https://upliftfood.com/blogs/news/the-gut-microbiome-brain-axis Dysbiosis and the gut-brain-immune axis The gut microbiota influences neurotransmission through the vagus nerve, connecting directly to the brain and modulating mood and behavior. The gut communicates with the immune system, affecting the distribution of immune cells, hormones, and metabolites  The gut-brain axis Gut and brain are also connected through neurotransmitters which control feelings and emotions. Many of these neurotransmitters are also produced by gut cells and the trillions of microbes living there. A large proportion of serotonin, which plays a key role in body functions as mood, sleep, digestion, etc., is produced in the gut. Gut microbes also produce a neurotransmitter called gamma-aminobutyric acid (GABA), which helps control feelings of fear and anxiety. Studies in mice have shown that certain probiotics can increase the production of GABA and reduce anxiety and depression-like behavior. https://www.healthline.com/nutrition/gut-brain-connection#TOC_TITLE_HDR_2  The gut-brain axis Gut microbes produce short-chain fatty acids (SCFA) such as butyrate, propionate and acetate by digesting fiber. Acetate—the most abundant SCFA and an essential metabolite for the growth of other bacteria—reaches the peripheral tissues where it is used in cholesterol metabolism and lipogenesis, and may play a role in central appetite regulation. Butyrate -is the main energy source for human colonocytes, can induce apoptosis of colon cancer cells, and can activate intestinal gluconeogenesis, having beneficial effects on glucose and energy homeostasis. Propionate -is transferred to the liver, where it regulates gluconeogenesis and satiety signalling through interaction with the gut fatty acid receptors. https://www.healthline.com/nutrition/gut-brain-connection#TOC_TITLE_HDR_2  The gut-brain axis - immunity The gut and microbes play a crucial role in regulating the immune system and inflammation by controlling the absorption of substances into the body and the elimination of waste products. Lipopolysaccharide (LPS) is an inflammatory toxin produced by certain bacteria. Excessive translocation of LPS from the gut into the bloodstream can induce inflammation. This phenomenon often occurs when the integrity of the gut barrier is compromised, allowing both bacteria and LPS to permeate into the circulatory system. Inflammation and high LPS in the blood have been associated with a number of brain disorders including severe depression, dementia and schizophrenia.  Microbiota and obesity TJ: Tight Junctions IEC: Intestinal Epithelial Cells Low-Density Lipoprotein Cholesterol (LDL-C) The exact taxonomic composition that constitutes a “healthy” gut microbiota is still unclear. Evident that microbial diversity is an essential component to host health. Compared to their lean counterparts, obese individuals have a markedly lower bacterial diversity, and decreased fecal microbial gene richness. Int. J. Mol. Sci. 2020, 21(8), 2890; https://doi.org/10.3390/ijms21082890  Dysbiosis and obesity An overgrowth of Firmicutes relative to Bacteroidetes is often associated with obesity and metabolic issues because they are efficient at extracting energy from food, which can lead to increased fat storage. FIAF:Fasting-Induced Adipose Factor A higher proportion of Bacteroidetes is generally considered beneficial and is associated with a leaner body composition and improved gut health. The microbiota of people with obesity contains lower proportions of Bacteroidetes and higher proportions of Firmicutes than those from people without obesity as is also seen in pregnancy.  Dysbiosis and obesity Antibiotics kill both the good and the bad Mice treated with antibiotics gained weight. Antibiotics mixed with animal feed makes them grow quicker. Children treated with antibiotics during the first 6 months have a 22% higher probability of being obese at 3 years. 12  Dysbiosis and obesity Most studies of overweight and obese people show a dysbiosis characterized by a lower diversity. Germ-free mice that receive faecal microbes from obese humans gain more weight than mice that receive microbes from healthy weight humans. Gut microbiota dysbiosis probably promotes diet induced obesity and metabolic complications by a variety of mechanisms including (i) immune dysregulation, (ii) altered energy regulation, (iii) altered gut hormone regulation, and (iv) proinflammatory mechanisms (such as lipopolysaccharide endotoxins crossing the gut barrier and entering the portal circulation. Data from both human and rodent studies has linked an obese phenotype to elevated circulating levels of plasma LPS. https://www.bmj.com/content/361/bmj.k2179  Dysbiosis and Gastrointestinal disorders Inflammatory Bowel disease (IBD) is traditionally divided into Crohn's disease (CD) and ulcerative colitis (UC). IBD involves immune-mediated inflammation and structural damage. Irritable bowel syndrome (IBS) is one of the most common gastrointestinal (GI) disorders. IBS is a functional disorder linked to gut sensitivity and motility changes without inflammation. The bacterial role has been largely investigated.  A significant reduction in the concentration of aerobic bacteria such as the Lactobacillus species in fecal samples from IBS patients compared to healthy controls.  Increasing evidence shows that IBS patients are affected with higher levels of stress and a negative emotional well-being, indicating the importance of the gut-brain axis.  Pathogenesis of IBS J Clin Med. 2023 Apr; 12(7): 2558.  Dysbiosis and IBS Under normal circumstances, mucus epithelium barrier confines microbes to the epithelial surface or intestinal lumen where homeostatic immune responses are induced to maintain barrier integrity and tolerance among commensal microbes. Once the barrier is breached by influx of inflammatory mediators, pathogens or any agents that provoke intense immune reactions, severe inflammation occurs and this will affect the intestinal environment, and changes the gut microbiota composition. Combination of low grade mucosal inflammation with visceral hypersensitivity and impaired bowel motility could be the underlying etiology for IBS pathogenesis. Front. Microbiol., 10 June 2019 | https://doi.org/10.3389/fmicb.2019.01136  Dysbiosis and IBS Diet significantly impacts the composition of the gut microbiome. Reduction in the intake of foods that are high in fermentable oligosaccharides, disaccharides, and monosaccharides and polyols (FODMAP) reduces GI symptoms and improves disease-specific quality of life in patients with IBS. At least 86% of patients with IBS report symptomatic benefit. FODMAPs are short-chain carbohydrates that are easily fermentable by gut bacteria into methane and hydrogen gasses but are poorly absorbed. The success of re-establishing intestinal homeostasis with fecal microbial transplant (FMT) in recurrent Clostridium difficile infection has inspired investigators with an interest in IBS. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6039952/  Fecal Microbiota Transplantation (FMT) Therapy (ulcerative colitis) Candida, a fungus that contributes to inflammation and gut barrier dysfunction FMT might reduce Candida abundance and restrict pro- inflammatory immunity during intestinal inflammation. https://doi.org/10.1016/j.chom.2020.03.006 Dysbiosis and inflammatory bowel disease(IBD) Compared the faecal microbiome of Crohn’s disease (CD) with patients having ulcerative colitis (UC) and with non-IBD subjects in a longitudinal study. Dysbiosis was found significantly greater in patients with CD than with UC, as shown by a more reduced diversity, a less stable microbial community and eight microbial groups were proposed as a specific microbial signature for CD. Although UC and CD share many epidemiologic, immunologic, therapeutic and clinical features, our results showed that they are two distinct subtypes of IBD at the microbiome level. https://gut.bmj.com/content/66/5/813  Dysbiosis and inflammatory bowel disease Increased harmful bacteria :Enterobacteriaceae high bacterial diversity Decreased tight High short-chain fatty acids junction (SCFAs) Anti-inflammatory signals balanced interaction between immune cells like Th17 and Th1 Microorganisms 2021, 9(4), 697  IBD and Environmental factors Hygiene hypothesis: lack of early microbial exposure may reduce tolerance of the adaptive immune response Factors at play: cleaner living, urbanization and increased antibiotic use  Probiotics vs prebiotics Probiotics are live bacteria that impart health benefits if eaten. However, not all probiotics are the same. Some probiotics have been shown to improve symptoms of stress, anxiety and depression. One small study of people with irritable bowel syndrome and mild-to- moderate anxiety or depression found that taking a probiotic called Bifidobacterium longum NCC3001 for six weeks significantly improved symptoms. Prebiotics, which are typically fibers that are fermented by gut bacteria, may also affect brain health. One study found that taking a prebiotic called galactooligosaccharides for three weeks significantly reduced the amount of stress cortisol in the body. https://www.healthline.com/nutrition/gut-brain-connection#TOC_TITLE_HDR_2