microbiota

halobiont

assemblages of different species that form ecological units - provides survival benefit for the different species involved

humans are holobionts

symbiosis

interaction between two different organisms living in close physical association, typically to the advantage of both e.g. nutritional benefits, transport benefits, protection

facts and figures

our gut microbiota contains tens of trillions of bacteria

• ten times more than human cells in our body

microbiota, in total can weigh up to 2kg

• can be considered as a endocrine organ on its own

our microbiota has co-evolved with us over millions of years

• changes in the microbiota mirror species divergence

the composition of gut microbiota in unique to each individual, just like our fingerprints

more than 1000 different known bacterial species can be found in human gut microbiota, with about 150 and 170 predominating in any given subject

microbiota and our health

important in digestion (metabolizes fiber to SCFAs)

also important in many other aspects of intestinal physiology

• barrier function - mucus secretion, epithelial proliferation and death, defensin production, tight junction permeability

• transport function - nutrient, electrolytes ad fluid

• hormone secretion from neuroendocrine cells

also important in many aspects of extra-intestinal physiology

• fat and sugar metabolism

• immune function

• cardiovascular function

• cognition

• mood

enhances: metabolism, immunity, cognition, socialization, coping with stress, physical fitness

normal composition of the microbiota

can be determined by 16S DNA sequencing

estimated to be > 1000 bacterial species in the human gut

belong to 9 phyla

• firmicutes

• bacteriodetes

• actinbacteria

• fusobacteria

• proteobacteria

• verrucomicrobia

• cyanobacteria

• spirochetes

• vadinBE97

bacteriodetes

communities determined by diet e.g. bacteriodes and prevotella

firmicutes

more dependent on genetic makeup e.g. clostridia and lactobacillus

the microbiota and age

baby: fetus is sterile. becomes inoculated with vaginal and skin microbes at birth - diversity increases through interacting with the environment

adult: microbiota has fully diversified (100 spp.) and stabilized

elderly: microbiota stability and diversity decreases

communication - the microbiota and SCFAs

colonic microbes are important in digestion of fiber to SCFAs - provides an important energy source for epithelial cells

SCFAs also have important roles in regulating our physiology

communication - the microbiota and bile acids

bile acids are produced by the liver to facilitate lipid digestion and absorption

90-95% are reabsorbed by the terminal ileum and recycled by the liver by the EHC

5-10% enter the colon and undergo bacterial metabolism

communication - the microbiota and bile acids

the colon expresses 2 receptors for bile acids

• TGR5 - cell surface G protein-coupled receptor. activated by conjugated bile acids

• farnesoid X receptor - nuclear receptor. activated by deconjugated bile acids. antagonized by UDCA

extent of FXR vs TGR5 activation is dependent on the makeup of the colonic microbiome

both FXR and TGR5 play critical roles in regulating

• intestinal function - motility, fluid transport, barrier function

• metabolic function - fat metabolism, glucose metabolism, energy expenditure

dysbiosis - alteration in the microbiota

imbalance in the normal levels of bacteria within the gut - usually associated with poor health or disease

the ratio of firmicutes to Bacteroidetes in the stool is a gauge of overall gut microbiota balance

antibiotic-associated diarrhea, Crohn’s disease, and ulcerative colitis are associated with decreased firmicutes and increased Bacteroidetes and a reduced gut biodiversity

Dysbiosis has been suggested to play a role in the development of type 2 diabetes (T2D). Patients with T2D have a lower F/B ratio than nondiabetic control

A higher ratio (i.e.. increased firmicutes and decreased Bacteroidetes) is associated with obesity

other disease associated with dysbiosis include: infectious diseases, IBS, cancer, atherosclerosis, autism, depression etc.)

fecal microbial transplantation

FMT is defined as the transfer of fecal material containing bacteria from a healthy donor into a diseases recipient

stool is collects from a donor (200-300g), mixed with saline and strained and placed into a patient by enema

>90% cure rate is C difficile-associated diarrhea