Gut Feeling 2024 Examining Microbiomes PDF

Gut Feeling: examining microbiomes and their impact. Simon Milling Image: cancer Research UK Where am I? Introduction Fundamentals in Microbiology RNA vs DNA viruses Adapt and Survive Global impacts of microbes Gut feeling Sensing Danger Antibiotic...

Gut Feeling: examining microbiomes and their impact. Simon Milling Image: cancer Research UK Where am I? Introduction Fundamentals in Microbiology RNA vs DNA viruses Adapt and Survive Global impacts of microbes Gut feeling Sensing Danger Antibiotic Resistance Parasites and immune system Vaccines Outsmarting the bugs Aims: - Describe methods that have revolutionised the microbiome field - Describe how communities of micro-organisms colonise us - Describe how microbial communities are important for our health - Describe how the microbiota contribute to disease I will introduce: - Methods that have revolutionised this field - Communities of micro-organisms that colonise us - How microbial communities are important for our health - How changes in the microbiota contribute to disease  Microbiota  Tens of trillions of microbes (1014)  Mostly in colon  Also SI, lungs, skin, teeth, everywhere…  80% non-culturable New Methods…  Technology Many bacteria still not cultureable, so use  16S sequencing  Whole Genome Sequencing + Metagenomics  Computation  16S Sequencing The 16S region of rRNA is conserved, with minor differences between groups of bacteria 16S vs WGS http://knowgenetics.org/whole-genome-sequencing/  16S vs WGS https://www.gatc-biotech.com/en/expertise/targeted-sequencing/16s-rrna-analysis.html  16S vs WGS 16S WGS Cost Low High Computation OK Intense Better - where Identity OK genome known Functions Inferred Accurate Bacterial Communities Development of microbiota Tamburini et al, Nature Medicine, 2016 Co-evolution Forter et al, Nature, 2017 Are you really 90% bacteria? https://doi.org/10.1016/ j.cell.2016.01.013 Properties of mucosal tissues Nature 2011 Amarugam et al Nature 2011 Amarugam et a Bacterial Communities  Colonise all body surfaces, especially mucosa  Communities differ at different sites  Bacteriodes is the most common genus in the colon  Communities are complex, stable, and interdependent  Affected by many factors, especially diet Human Health  Human Health  Metabolise complex carbohydrates from plants —> Short Chain Fatty Acids  Synthesis of micronutrients- vit. B3, B5, B6, B12, biotin, tetrahydrofolate, vit K.  Limit pathogen colonisation  Short Chain Fatty Acids Include butyrate (most abundant), acetate and propionate Produced by bacterial fermentation of dietary fibre, mostly in colon Main energy source for epithelial cells Butyrate has anti-inflammatory effect on intestinal epithelial cells Involved in differentiation of colonic Tregs and ameliorates colitis in mice* There are other important bacterial metabolites! *Furusawa, Y. et al. Nature 504, 446–450 (2013) Short Chain Fatty Acids Huffnagle, Nature Medicine News & Views 2013  Human Health Should I take probiotics? Live Lactobacillus casei shirota strain, 6.5 billion per 65 mL bottle. Global market $6970 M in 2021 How many survive stomach acid and colonise? Limited evidence for efficacy. But little harm. Disease  Disease Associations Acne Inflammatory Bowel Disease Cardiovascular Disease Halitosis Obesity Irritable Bowel Syndrome Type II Diabetes Arthritis Stroke Chronic Fatigue Syndrome Alopecia Colorectal Cancer Multiple Sclerosis Peridontal Disease CAUSE AND EFFECT? Inflammatory Bowel Disease  Includes Ulcerative Colitis, Crohn’s disease  Interplay between:  Host genetic factors  Innate and adaptive immune response  The microbiota! Inflammatory Bowel Disease Pictures: Dan Gaya, Glasgow Royal Infirmary  Inflammatory Bowel Disease  Infiltration of bacteria drives inflammation  Lesions generated by immune response against microbes.  Abnormal microbial colonisation might contribute to disease.  Cause or a consequence? Nature Reviews Gastroenterology and Hepatology 9, 599-608 (October 2012) Inflammatory Bowel Disease The intestinal immune system is specialised to deal with the food and bacteria in the gut Clostridium Difficile Infection jamanetwork.com/journals/jama/fullarticle/1920973  In Glasgow... Faecal transplants used to cure Clostridium difficile By James Gallagher Health reporter, BBC News Transplanting faecal matter from one person to another - the thought might turn your stomach, but it could be lifesaving. Some doctors are using the procedure to repopulate the gut with healthy bacteria, which can become unbalanced in some diseases. Dr Alisdair MacConnachie, who thinks he is the only UK doctor to carry out the procedure for Clostridium difficile infection, describes it as a proven treatment... * http://www.bbc.co.uk/news/health-15 113440  Curing the microbiota? Faecal microbiota transplantation (FMT) Full spectrum of microbial components Used by Ge Hong 2000 years ago in China 90% success via colonoscopy for C. difficile Much less success for other conditions Risks? Exposure to unknown pathogens May transfer other illness… Kamada, N., Seo, S.-U., Chen, G. Y. & Núñez, G. Nat Rev Immunol 13, 321–335 (2 Summary: - Methods that have revolutionised this field - Communities of micro-organisms that colonise us - How microbial communities are important for our health - How changes in the microbiota contribute to disease The End 💩