The Human Microbiome, Study notes of Biology

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THE$ROLE$OF$THE$

MICROBIOME$IN$HUMAN$

HEALTH$

MSC$IN$FOOD$BUSINESS$MANAGEMENT$AND$

TECHNOLOGY$

Catherine$Corcoran$

X00124832!

Table!of!Contents!

1.! INTRODUCTION:,..............................................................................................................,3!

2.! ROLE,OF,MICROBIOME,IN,THE,IMMUNE,SYSTEM:,...............................................,4!

2.1.T,cell,Induction,..........................................................................................................................,4! 2.1.1.!Figure!1:!Butyrate!function!produced!by!gut!microbiota![18]!.......................................!5! 2.2.,Dysbiosis,and,modifying,of,the,gut,microbiota,.............................................................,5!

3.! ROLE,OF,MICROBIOME,IN,MENTAL,HEALTH:,........................................................,6! 4.! ROLE,OF,MICROBIOME,IN,DIGESTION:,....................................................................,7! 4.0.1.!Figure2:!Fermentation!of!undigested!carbohydrates![17]!..............................................!7! 5.! THEAPEUTIC,APPROACHES,.........................................................................................,8! 5.1.Probiotics,....................................................................................................................................,8! 5.2.,Prebiotics,...................................................................................................................................,8! 5.3.,Nutraceuticals,in,mental,health;,........................................................................................,9! 5.3.1.! Figure!3:!Beneficial!role!of!probiotics![4]!.........................................................................!10! 5.4.,Phage,therapy,.........................................................................................................................,10! 5.5.,Microbiota,transplantation,................................................................................................,11! 5.6.,Quorum,sensing,inhibitors,.................................................................................................,11! 6.! Discussion:,.....................................................................................................................,12! 6.0.1.!Figure!4:!!Future!therapies!for!dysbiosis![1]!.......................................................................!12! 7.! BIBLIOGRAPHY:,............................................................................................................,13! !

and! metabolomics! has! allowed! for! the! metabolized! products! of! microbes! to! be! scrutinized! and! such! advancements! provide! a! snapshot! for! the! synergism! of! prebiotics!and!probiotics!in!health!and!disease![7].!! ! The!GIT!and!the!brain!are!importantly!linked![7].!“Going!with!you!gut!instinct”!can! be! interpreted! as! receiving! signals! from! the! equivalent! of! your! second! brain.! Understanding! the! relationship! of! the! gut! with! mood,! health! and! digestion! is! a! revolutionary!path!in!science![14].! ,

2. ROLE!OF!MICROBIOME!IN!THE!IMMUNE!SYSTEM:!

The! gut! flora! influences! health.! Shortcomings! in! beneficial! gut! bacteria!are! tied! to! diseases!such!as!inflammatory!bowel!disease!(IBS),!antibiotic!associated!diarrhoea,! colon! cancer! and! others.! Bacterial! colonization! in! natural! delivery! inaugurates! as! infants! come! in! contact! with! the! maternal! faecal! and! vaginal! microbiota,! Babies! birthed! by! caesarean! section! establish! a! diverse! set! of! bacteria! because! of! the! sterile!nature!of!caesareans!and!the!absence!of!maternal!faecal.!Breast^!fed!infants! house! different! bacteria! to! that! of! formula! fed! babies,! such! differences! can! be! the! trigger!of!vulnerability!to!immune!dependent!diseases!later!in!life![10].!! !

2.1.T!cell!Induction!

The! intestinal! mucosa! layer! creates! an! obstacle! for! pro! inflammatory! compounds! and! uptake! of! antigens! [12].! The! intestinal! lumen! is! comprised! of! gastric! acid,! enzymes!and!Immunoglobulin!A!(an!antibody!important!in!mucosal!immunity)!and! is! the! first! line! of! resistance! to! pathogenic! bacteria.! The! native! bacteria! inhibit! pathogens! and! induce! Tcells,! a! white! blood! cell! important! for! healthy! immune! systems! [2].! The! category! of! microbial! contact! early! in! life! is! influential! in! the! development!of!T^helper!cell!lineage.!Understanding!the!role!of!microbiota!in!Tcell! responses! to! infection! is! important.! Yukihiro! et! al! explained! that! commensal!

bacteria_!_ growth!is!accountable!for!Th17!and!Treg!induction!(Fig!1)[12].!Segmented! Filamentous!bacteria!(SFB)!positive!mice!allow!for!the!development!of!TH17!cells!in! the!small!intestine.!Th17!cells!are!a!type!of!CD4+!T!cells!that!are!vital!for!a!positive! immune!response!to!invasive!pathogens![15].! ,

2.1.1.!Figure!1:!Butyrate!function!produced!by!gut!microbiota![18]! !

2.2.!Dysbiosis!and!modifying!of!the!gut!microbiota!

Inferior!microbial!contact!early!in!life!or!life!style!changes!can!result!in!alterations! in! the! function! and! composition! of! micrbiota! (Dysbiosis).! Dysbiosis! is! associated! with!metabolic!and!immune!diseases!such!as!crohn’s!disease!and!ulcerative!colitis! IBD!and!IBS![11]![13].!! ! IBS! patients! have! demonstrated! a! common! finding! of! decreased! amounts! of! BIfidobacterium,!Lactobacilli! and!increased!aerobes.!Antibiotic!use!is!the!main!cause! of! IBS.! Atopic! dermatitis! sufferers! (Eczema)! have! also! been! shown! to! have! low!

Certain! gut! bacteria! have! been! reported! to! participate! in! mood! states.! Depression! has! been! linked! with! IBS! and! leaky! gut! [6][8].! Maes! et! al! carried! out! a! study! reporting! that! 35%! of! clinically! depressed! individuals! have! suffered! from! a! leaky! gut! and! around! 30%! of! those! with! severe! depression! have! IBS! irritable! bowel! syndrome![7][8][6].! !

4. ROLE!OF!MICROBIOME!IN!DIGESTION:!

The! gut! flora! is! important! in! converting! nutrients! into! calories.! Variations! in! bacterial!composition!are!found!in!obese!humans!and!mice.!The!microbiome!lends!a! biological! pathway! for! the! fermentation! of! these! oligosaccharides! resulting! in! the! growth!of!additional!beneficial!microbes!and!short!chain!fatty!acids!such!as!acetate,! butyrate,! lactate! and! ethanol! (Fig! 2)! [12].! SCFA’s! are! pivotal! regulators! of! host! metabolism! and! immunity! [13].! Butyrate! is! favoured! by! colonic! bacteria! as! the! primary! means! of! energy! and! has! been! displayed! to! inhibit! the! growth! of! colonic! cancer!cells!in!vitro![12]![2].!

4.0.1.!Figure2:!Fermentation!of!undigested!carbohydrates![17]! !

5. THEAPEUTIC!APPROACHES!

5.1.Probiotics!

Probiotic! therapy! administers! beneficial! bacteria! to! improve! the! intestinal! microbial! situation! of! a! host! [7].! Probiotics! are! live! microorganisms! administered! within! functional! foods! such! as! dairy! products! that! have! concurred! numerous! health! benefits! to! the! host.! Lactobacilli! and! Bifidobacterium! are! at! present! the! prominent! probiotic! bacteria! used! commercially! in! the! food! industry.! Probiotics! intensifies!the!host’s!defence!against!pathogens.!The!mucosal!epithelial!cell!barrier! is! the! first! line! of! defence! against! the! attack! of! pathogens.! Optimizing! mucin! generation! and! lessening! gut! permeability! further! thwarts! the! invasion! of! pathogens.! Studies! have! shown! that! probiotic! microorganisms! increase! mucin! production!in!cell!culture![2]!and!reduce!gut!permeability!in!mice![3]!Surface!layer! proteins! on! Lactobacillus! crispatus! and! Lactobacillus! helveticus! are! important! for! the!binding!of!probiotics!to!cell!surfaces!in!hosts![4].!Probiotic!therapy!can!be!used! to! counteract! many! illnesses! for! e.g.! ulcerative! colitis! reoccurrence,! antibiotic! induced^diarrhoea!and!crohn’s!disease![2].! !

5.2.!Prebiotics!

Prebiotics! are! non^digestible! carbohydrates! that! prompt! the! growth! of! advantageous! bacteria! already! habituating! in! the! gut! such! as! Lactobacilli! and! Bifidobacterium! thus! enhancing! the! health! of! the! host.! Oligosaccharides! such! as! cellulose!are!crucial!in!the!diet![12]![13].!Prebiotic!effects!have!been!focused!on!the! colon! but! their! power! spreads! beyond! the! GI! tract,! they! also! prompt! beneficial! microbial!growth!within!the!gut!flora.!They!may!directly!enhance!immunity,!guard! against!pathogens!and!assist!in!the!absorption!of!calcium!or!magnesium!minerals.!! Faecalibacterium! prausnitzii ,! an! anti^inflammatory! commensal! bacterium! that! is! lacking! in! crohn’s! disease! has! the! ability! to! break! down! prebiotics,! producing! butyrate.! Prebiotic! fermentation! by! Lactobacilli! and! Bifidobacterium,! create! metabolites!that!can!be!degraded!by!other!bacteria!such!as! Anaerostipes!caccae.! A!

5.3.1. Figure!3:!Beneficial!role!of!probiotics![4]! ! In! the! last! century! the! dietary! intake! of! w! 3! fatty! acids! has! depleted! in! western! countries!and!has!been!replaced!by!omega!6!rich!oils!(corn!and!sunflower)!and!this! may!well!be!the!reason!for!high!levels!of!severe!depression.!EPA’s!in!w!3!fatty!acids! are! the! building! blocks! of! the! brain! and! whilst! Omega! 3! is! an! anti^inflammatory,! Omega!6!has!proven!to!have!a!counter!effect![7].!The!combination!of!probiotics!and! Omega!3!has!huge!potential!in!the!treatment!of!MDD.! , ,

5.4.!Phage!therapy!

The! use! of! prebiotic,! probiotics! (Functional! foods),! as! well! as! bacteriophage! have! been!developed!as!methods!for!harnessing!alterations!in!the!microbial!community! and!for!treating!diseases!such!as!diabetes!and!obesity.!Phage!therapy!involves!the! utilization!of!bacterial!viruses,!bacteriophages!as!anti!microbial!agents!by!allowing! the!phage!to!attach!to!receptors!within!the!host!membrane!and!subsequently!inject! their!genetic!makeup!into!the!bacterium.!“Viral!proteins”!are!then!synthesized!using! the! host’s! “translational! memory”.! Phage! therapy! benefits! the! human! microbiome! and!therefore!the!host’s!health.!To!decide!on!specific!phage!as!a!therapeutic!agent,!

the! pathogen! causing! the! disease! must! be! known.! When! this! is! not! possible,! a! collection! of! phage’s! can! be! used! but! this! can! impart! negative! implications! on! the! microbial!community![1]. ,! ,

5.5.!Microbiota!transplantation!

Clostridium! difficile! infection! (CDI),! a! gastrointestinal! disease! is! triggered! by! distress! in! the! intestinal! microbiota.! The! incidence! of! CDI! has! escalated! recently.! CDI’s! are! generally! treated! with! a! cocktail! of! antimicrobials! and! although! it! does! resolve!CDI,!the!therapy!also!diminishes!the!levels!of!beneficial!bacteria!habituating! in! the! gut.! Faecal! microbiota! transplantation! (FMT)! is! an! alternative! treatment! to! antibiotics! that! is! proving! to! be! successful.! FMT! involves! the! administration! of! faecal!flora!from!a!healthy!individual!into!a!CDI!patient.!FMT!treatment!has!not!only! alleviated! the! symptoms! of! CDI! in! patients! but! also! has! proven! to! restore! normal! microbial! levels! in! the! gut! in! just! a! few! weeks.! There! are! reports! of! the! use! of! a! ‘synthetic! probiotic! pool! mixture”! as! a! reliable! alternative! to! treating! people! with! CDI![5].! !

5.6.!Quorum!sensing!inhibitors!

Bacteria! communicate! use! quorum! sensing! systems! enabling! them! to! synchronize! genetic! expression.! Innovative! compounds! that! disrupt! QS! systems! have! been! developed!recently.!An!understanding!of!all!parts!of!signal!transduction!involved!in! quorum! sensing! is! necessary! to! deliver! a! picture! of! how! bacterial! cells! communicate,! so! as! to! lessen! pathogenic! colonization.! More! knowledge! on! “metagenomics”,! a! way! to! study! uncultured! microbes! directly! from! their! natural! source!and!“metabolomics”!will!help!to!decipher!the!interaction!of!bacteria!and!the! immune!system!![1].!

7. BIBLIOGRAPHY:!

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14. Then!brain!gut!connection.!Available:! http://www.hopkinsmedicine.org/health/healthy_aging/healthy_body/the^brain^ gut^connection.!Last!accessed!10th!Dec!2015.!
15. Yukhiro!F,!Yuuki!O,!Koji!H.!Commensal!microbiota!regulates!T!cell!fate!decision!in! the!gut , !Seminars!in!Immunopathology!2015;!37:17^25.!
16. Lee!WJ,!Hase!K.!Gut!Microbiota^!generated!metabolites!in!animal!health!and!disease,! Nature!Chem!Biology!2014;!10:!416^424!

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