Microbiota Flashcards

Question

The obesity epidemic

Answer 1

-Obese individuals have a distinct gut microbiome from lean individuals -Several confounder exist: diet, genetics, environment, etc -Twin: obese and lean; monozygotic have different gut microbial communities; dizygotic twin have even more different gut microbial communities -use animal models to determine the role of gut microbiome

Answer 2

Leptin mutant+normal lean mouse

Answer 3

Hormone made of fat cells that regulates the amount of fat stored in the body, “satiety” hormone Animal models of Type 2 diatbetes

Answer 4

Obese mice and WT mice fed the same diet Amplicon sequencing (variable region of 16S rDNA) Obese mice have significantly higher proportions of Firmicutes : Bacteroidet

Answer 5

Transfer gut microbial community from the obese individual to lean individual. The mice putting on more weight despite controlling for the diet After confirmation of microbiome transfer, ratios of Fimicutes:Bacteriodetes were increased in the recipient mice Mice receiving feces from obese mice had more body fat after 2 weeks DESPITE no differences in the amount of food eaten per group

Answer 6

Shotgun sequencing of gut microbiome form lean and obese littermate mice Genes used to harvest energy from carbohydrates higher in obese mice Fecal calorimetry measurements showed that obese mice had less energy left in their feces than lean mice

Answer 7

Germ-free mice were colonized with feces form twins discordant不一致 for obesity. Mice receive obese twin microbial community would put on body weight Diet remains key: Additional data showed that a “lean” microbiota cannot colonize well when mice are fed high fat/low fiber diets Subsequent studies show the altered F:B ratio is not always present and that housing conditions remain important

Answer 8

Took 7 day clindamycin For nine months after exposure, only one resistance strain detected Even after 24 months, gut microbiota diversity remained low

Answer 9

Antibiotics decrease gut bacterial diversity Particularly disruptive during early childhood At sub-therapeutic doses, antibiotics can promote weight gain. Some people give livestock sub-therapeutic doses to increase their weight

Answer 10

Antibiotics can promote ”pathobiont” expansion • Pathobionts: members of the microbiota in healthy hosts, normally don’t cause disease Most common adverse effect of clindamycin is **Clostridioides difficile**-associated diarrhea

Answer 11

~2% of the population are “healthy carriers” Present in the environment, spore formers • Healthy microbiota: **colonization resistance** • Highest risk factor: broad spectrum, antibiotic treatment

Answer 12

Other bacteria already take the niche to prevent C. difficile growth Already have C. difficile but other bacteria produce some molecules will limit the expansion of C. difficile

Answer 13

Treatment can’t be to use another antibiotics to against it 1st line treatment: discontinuation of antibiotic usage, metronidazole or vancomycin course

Answer 14

Fecal microbiota transplant

Answer 15

FMT: Possible last-resort treatment for patients suffering from recurring C. difficile infections Infusion of fecal bacteria from a healthy individual into a recipient -get stool sample from healthy patient -screen the sample -no other pathogen in it -transplant the sample to patient by colonoscopy or infusion Even a better treatment

Answer 16

Up to 25% some patients have treatment resistant or recurrent C. difficile. Multiple relapses in the same patient are common, and up to 10 or more bouts of relapsing colitis have occurred in some patients C. difficile infections are linked to 14,000 deaths in the U.S. yearly.

Answer 17

Total community transplant other possible pathobionts and/or pathogens - how to choose the correct “healthy” donor? - what is a “healthy” microbiome? - more data comes out correlating certain microbiome constituents with more and more diseases… - Vertical transmission of microbiome (mother to child): considerations for future generations? Society buy-in (taboo of fecal matter)

Answer 18

Also considered for many diseases: inflammatory bowel diseases (ulcerative colitis and Crohn’s disease), autoimmune disorders, metabolic syndrome, obesity, diabetes, multiple sclerosis, Parkinson’s disease, … • More challenging (chronic conditions) • More studies needed to define the best indications, optimal timing, frequency, mode of delivery, and optimal donor for each patient • Several clinical trials in progress • Other ways to manipulate microbiome: probiotics, prebiotics, diet, bacteriophages, …

Answer 19

Short chain fatty acids (SCFAs) are the fermentation end products of dietary carbohydrates. SCFA have immunoregulatory properties (pro-, anti-inflammatory). Butyrate acts as an energy source for enterocytes. Bacterial metabolites, such as SCFAs and neurotransmitters, can cross the blood-brain barrier (BBB) and regulate neurological functions Blood-brain barrier: highly selective semipermeable barrier of cells restricting access of molecules from blood to brain

Answer 20

Bacillus: Dopamine, norepinephrine Bifidobacterium: GABA (gamma-aminobutyric acid) Enterococcus: Serotonin Escherichia: Norepinephrine, serotonin Lactobacillus: Acetylcholine, GABA Streptococcus: Serotonin Immune cells and cytokines cross the BBB and can regulate neurological functions, including the hypothalamic-pituitary-adrenal axis (HPA) All these molecules are active in both the brain and the gut

Answer 21

Many diseases have co-occurring pathologies: – Up to 50% of adults with IBD and 33% of patients with IBS have pulmonary inflammation or impaired lung function – Individuals with asthma have functional and structural changes in their gut microbiota – Changes in the oral microbiome are associated with preterm birth and abortions – Patients with rheumatoid arthritis have a higher prevalence of periodontal disease – 7-11% of patients with IBD also have psoriasis, and the prevalence of IBD in individuals with psoriasis is 4 times

Answer 22

live microorganisms which when administered in adequate amounts confer a health benefit to the host

Answer 23

Inadequate studies: low sample size, quality of study design, lack of in vivo data, self-reported diagnostics and measurements, lack of details about probiotic strains used, … 还有安慰剂效应 • Limited mechanistic understanding of effects of current probiotics • Probiotic industry largely unregulated • Publication of negative results required • Need for a standardized and validated measure of “health benefit to the host” • No adequate tests to predict functionality of probiotics in the human body Information still required: strain(s)of probiotics, dose, duration, frequency, timing, indications, and side-effects • Rare cases of infections associated with probiotics • Transferrable microbial properties (antibiotic resistance genes, virulence genes, …) • Effectiveness of probiotic for altering a disease state is not provided currently

Answer 24

Antibiotics: ciprofloxacin and metronidazole 7-day treatment in humans, 14 days in mice Resulted in significant decrease in gut bacterial diversity Bi-daily probiotics administration (same 11-strain cocktail) to 21 human volunteers 3 test group Probiotics, auto FMT, spontaneous recovery

Answer 25

• Mice with a native gut microbiota are not colonized by probiotics. Antibiotics mildly enhance probiotic colonization in mucosal layers. • In humans, probiotic colonization is site- and person-specific. Antibiotics significantly enhance probiotic colonization in mucosal layers • After antibiotics exposure, **probiotics delay gut microbiome reconstitution and its metabolism.** • In contrast, **FMT from the same person (autologous FMT) restores mucosal microbial diversity and metabolism**

Answer 26

Worm Free-living organisms and parasites of most animals (almost universal feature of vertebrate animals) and plants Three major assemblages of parasitic helminths recognized: nematodes, cestodes, and trematodes Helminth infection concerns 25% of the world population

Answer 27

• Symptoms of helminth infections: diarrhoea, abdominal pain, weakness, reduced nutritional input, chronic intestinal bleeding (causing anemia), intestinal obstruction and rectal prolapse, death • Co-infection common • Modulate host immune response (induce Th2 response), allowing for decade-long infections. • Conflicting reports that helminths protect from malaria (Plasmodium sp.)

Answer 28

Autoimmune disorders Vs. Helminths infestation

Answer 29

Intestinal helminths possess immunomodulatory capacities and can alleviate bleeding in IBD. Their interactions with the gut bacteria can alleviate asthma symptoms. Have been shown to decrease the number of Bacteroides species involved in intestinal inflammation

Answer 30

Frequency, duration, which worm(s)? Is the whole/live worm needed? What are the direct effects of the helminths on the (human) host? Interaction with other chronic or acute diseases?

Answer 31

Viruses infecting bacterial, exist everywhere bacteria are present Can be recognize by immune system Self-replicating obligatory parasites without inherent metabolism High morphological diversity Typically outnumber bacteria 10:1

Answer 32

DNA polymerase restriction enzymes CRISPR

Answer 33

DNA and RNA phages (circular, linear, ss and ds) Phages with capsid or envelope Highly mosaic structure

Answer 34

No common genetic marker (no 16S rDNA equivalent), mutate so fast Limited, incomplete databases

Answer 35

Lyric cycle Lysogenic cycle 2 variations of lysogenic cycle -Chronic cycle -pseudolysogeny cycle

Answer 36

Majority of DNA phages RNA phages mostly link to diet Most phages are integrated in bacterial cells (prophages) Unique communities, temporally stable, high similarity between relatives and household members (“core phageome” – Manrique et al., 2016, PNAS) Can directly/indirectly modulate immune response Phage to bacteria ratio lower than other systems (between 0.1 and 3) Caudovirales (Myoviridae, Podoviridae, Siphoviridae), Microviridae, crAssphage, Lak phages

Answer 37

Healthy Infant: Majority lytic phage highly abundant but not diversified Healthy adult: Mostly prophages, integrated less diversified, higher abundance of microbial community Inflamed gut: more extracellular viruses, less diversified bacteria Disease-specific changes in virome diversity, increased phage richness, increased abundance of free phages

Answer 38

Phage has limit host range Phage might encode antibiotic gene Type 2, 3, maybe 4 secretion system encoded by phages

Answer 39

• Can phages be used as biomarkers? • Can we use phages to manipulate gut bacterial communities? • Are phages shaping the microbiota-immune cross-talk?

Answer 40

Height-for-age > 2 STDEV below the WHO Child Growth Standards median Stunting affects 22% of children <5 years old Irreversible after the first 2-3 years of life poor maternal health and nutrition, inadequate feeding practices, and repeated infections.

Answer 41

Healthy and stunted phages change gut bacterial communities in an age-specific manner Stunted phages allow for Proteobacteria to develop in an age-specific manner Results suggest an intervention time window, under the age of 23 months, for microbiome manipulation

Answer 42

bacteria need to grow with other members in the community

Microbiota Flashcards

(66 cards)