Microbiome.pdf

Microbiome  Microbiome Microbiome Background ▪ The term “microbiota” was first introduced in the early 1900s to describe the multitude of microorganisms. ▪ Collectively referred to as “the hidden organ,” thes...

Microbiome  Microbiome Microbiome Background ▪ The term “microbiota” was first introduced in the early 1900s to describe the multitude of microorganisms. ▪ Collectively referred to as “the hidden organ,” these microorganisms contribute significantly more genetic information 15 times than the human genome itself. The Concept of Microbiota and Microbiome: ▪ Although “microbiota” and “microbiome” are often used interchangeably, they have distinct meanings. Microbiota ▪ Refers to the living microorganisms found in a specific environment. Microbiome ▪ Encompasses the genetic material, metabolites, structural elements, and environmental conditions of these microorganisms. Composition & Diversity of Microbiota: ▪ Gut, oral cavity, lungs, vagina, and skin harbor microbiota. ▪ Gut microbiota being the most comprehensive in terms of diversity and number. ▪ This community mainly consists of major phyla such as Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, Fusobacteria, and Verrucomicrobia. Gut Microbiome ▪ A total of 1014 bacteria already represent the gut microbiome, and 1011 bacteria flow each day from the pharynx to the stomach. ▪ Changes in the gut microbiome are associated with diseases, but frequently, it is not known if this is a cause or an effect. ▪ Under normal conditions, formation of the adult microbiome occurs over the first 3 years of life and is affected by life events such as weaning, starting solid food, and primarily cessation of breastfeeding. 2 Microbiome Factors Influencing the Gut Microbiome ▪ At birth, the most common bacteria are aerobic bacteria such as 1- Age Enterococcus and Staphylococcus. Later, anaerobes prevail, with a prevalence of Firmicutes and Bacteroidetes. ▪ A vegetarian, fiber-rich diet promotes beneficial bacteria such as 2- Diet Firmicutes and Bacteroidetes. Host ▪ Innate immunity genes affect microbiome composition. 3- Genetics ▪ Athletes tend to have lower inflammatory markers and reduced 4- Exercise dysbiosis. ▪ Negatively impacts microbiome diversity, leading to distinct 5- Smoking differences between smokers and non-smokers. ▪ Antibiotics like clindamycin and vancomycin decrease the 6- Antibiotics diversity of beneficial bacteria such as Bacteroides and Ruminococcus. Functions of Gut Microbiome ▪ The gut microbiota has the capacity to metabolize dietary fibers not Metabolic Function ▪ metabolized by digestive enzymes that help in food fermentation. ▪ Biosynthesis of vitamin K. ▪ The intestinal surface represents an important barrier, and the Protective microbiome contributes to its stability. Function ▪ Pathogen protection. ▪ Immune response stimulation. ▪ Under normal conditions, the microbiome contributes to maintaining Structural the integrity of the gut epithelium. Function ▪ The dysbiosis produced by Escherichia coli and Clostridioides difficile facilitates the back diffusion of cytokines. 3 Microbiome Metabolites Produced by Gut Microbiota & Their Functions Bile Acid Metabolites {including ▪ Regulate bile acid, cholesterol, lipid, glucose, and deoxycholic acid and lithocholic activate host nuclear receptors and cell signaling acid} pathways. Short-chain fatty acids ▪ Regulate food intake and insulin secretion, also aid metabolites in maintaining body weight. Branched-chain fatty acids {including isobutyrate} ▪ Histone deacetylase inhibition, increased histone acetylation. Indole Derivatives ▪ IPA exhibits neuroprotective effects, acts as a {including indoxyl sulfate and IPA} powerful antioxidant and regulates intestinal barrier function. Lipopolysaccharide, ▪ Epigenetic regulation of genes in colorectal cancer, peptidoglycan, lipoteicholic acid modulation of chromatine structure and transcriptional activity. Phenolic Derivatives {including 4-OH phenylacetic acid, ▪ Exhibit antimicrobial effect, maintain intestinal urolithins, enterodiol and 9- prenylaringenin} health and protect against oxidative stress. Choline Metabolites ▪ Regulating lipid metabolism, and glucose synthesis {including choline, trimethylamine contribute to the development of cardiovascular Noxide, disease. and betaine} Polyamines ▪ Sustaining the high proliferation rate of intestinal {including putrescine, spermidine epithelial cells enhances intestinal barrier integrity and spermine} and enhances the systematic adaptive immune system. 4  Microbiome Examples of gut microbiota-derived metabolites and their beneficial effects on human health Metabolite Pathway Microbial Agent Health Benefits Butyrate Carbohydrate Clostridia; ▪ Increased intestinal barrier Metabolism Faecalibacterium function. prausnitzii; Coprococcus catus; ▪ Modulate intestinal macrophage Anaerostipes hadrus function. ▪ Suppression of colonic inflammation. ▪ Improvements in insulin sensitivity. Propionate Carbohydrate Prevotella copri; ▪ Suppression of colonic Metabolism Blautia obeum; inflammation. Coprococcus catus; Roseburia ▪ Decreased innate immune inulinivorans response to microbial stimulation. ▪ Protection from allergic airway inflammation. ▪ Improvements in insulin sensitivity and weight control in obese mice. Indole Tryptophan Lactobacillus; ▪ Maintenance of host-microbe Metabolism Bifidobacterium homeostasis at mucosal longum; Bacteroides surfaces via IL-22. fragilis ▪ Increased barrier function. ▪ Modulation of host metabolism. Indole-3- Tryptophan Lactobacillus ▪ Maintenance of mucosal aldehyde Metabolism homeostasis and intestinal barrier function via increased IL-22 production. ▪ Protection against intestinal inflammation in mouse. 5 Microbiome Interconnected Gut Axis ▪ Lactobacillus, Bifidobacterium, Enterococcus, and Streptococcus are among the principal producers of neurotransmitters. ▪ A Mediterranean diet rich in vegetables and fibers stimulates the activity and growth of beneficial bacteria for the brain. ▪ More than 20% of patients with gut dysbiosis are affected by sleep disorders and depression. ▪ Multiple sclerosis (MS): there is Gut-Brain often a higher abundance of Axis Firmicutes and a notable absence of Fusobacteria. ▪ Alzheimer’s disease (AD): decreased presence of Firmicutes and Actinobacteria. ▪ Parkinson’s disease (PD): show lower production of short-chain fatty acids (SCFAs) and a reduction in Faecalibacterium prausnitzii, which are responsible for producing these beneficial substances. Gut-Heart Axis ▪ Linked to cardiovascular diseases, atherosclerosis, and hypertension. Gut-Lung Axis ▪ Connected to chronic obstructive pulmonary disease. Gut-Liver Axis ▪ Related to liver inflammation and non-alcoholic fatty liver disease. Gut- Pancreas ▪ Associated with diabetes and pancreatic inflammation. Axis Gut-Bone Axis ▪ Linked to osteoporosis and bone demineralization. Gut-Muscle Axis ▪ Connected to muscle fragility and sarcopenia. Gut-Skin Axis ▪ Related to dermatological conditions like acne and psoriasis. Gut- Reproductive ▪ Connected to fertility issues and ovarian dysfunction. Axis 6 Microbiome Gut-Kidney Axis ▪ Linked to chronic kidney disease and inflammation. Gut-Bladder Axis ▪ Associated with urinary tract infections and bladder dysfunction. Some examples of potentially harmful gut microbiota bacterial species Bacteria Associated Associated Disease States Physiological Changes Activate CD4+ T cells ▪ Increased with animal-based diet. Bacteroides ▪ Increased in obesity. Promote pro- ▪ Increased in colitis. Bilophila inflammatory immunity ▪ Decreased in autism. ▪ Increased after smoke exposure. ▪ Increased in autism and Rett syndrome. Promote generation Clostridium Th17 cells ▪ Positive correlation with plasma insulin and weight gain. ▪ Increased in type 2 diabetes. ▪ Clostridium perfrigens increased in old age. ▪ Increased in inflammatory bowel TLR activation Escherichia Coli disease. ▪ Increased in type 2 diabetes. Sugar fermentation ▪ Only two species are pathogenic: Neisseria Neisseria meningitides and Neisseria gonorrhoeae. 7  Microbiome Treatment & Perspectives Dysbiosis treatment involves prebiotics, probiotics, and fecal microbiota transplantation. ▪ Prebiotics: Dietary products that enhance indigenous microbiota or promote specific bacterial growth. ▪ Probiotics: Live beneficial bacteria helping to rebalance gut microbiota. ▪ Beneficial bacteria noted for re-equilibrating dysbiosis include Akkermansia muciniphila, F. prausnitzii, and B. uniformis. ▪ Fecal microbiota transplantation: Transfer of fecal microorganisms from healthy individuals to restore gut microbiota. 8