M4-Lecture1 Flashcards
The microbiome - Function and Role in DOHaD
What is community of native bacteria that live in and on human body:
10X of them
Microbiome
Role of microbiome:
Human health and disease
understudied
Microbiome consists of microbes - helpful and harmful.
True
Most microbiome are symbiotic meaning
But in smaller #s are pathogenic (no problem though, still coexist)
Both human and microbiota benefit
What could disrupt the balance of symbiotic:
Infectious illnesses, certain diets, prolonged use of antibiotics, dysbiosis
Gut microbiome compose of:
Bacteria (500-1000 dif. species), yeast, viruses
Two dominant divisions of bacteria microbiome:
Firmicutes
Bacteriodetes
Actinobacteria
We have about 100 trillion of microbes (10 to 1 with our cells)
True
See diagram
Microbiome may weight 5 pounds
Microbiome encodes over 3 million genes, producing what:
Metabolities
Humans only 23,000 genes
Gut microbiota vary according to intestine anatomical:
True
Intestine anatomical vary according to what:
pH, O2 tension, digesta flow rates, substrate availability, host secretions.
Each person has unique microbiota profile:
Yes
Role of microbiome in the host:
Nutrient metabolism (synthesis of vitamins), structural integrity of gut mucosal barrier, immunomodualtion, fat storage, produce SCFA by fermentation, modulate CNS, protection from harmful pathogens.
Human gut microbiota are shaped in early life
True
Factors that determine gut microbiota composition:
Birth gestational date, type of delivery, methods of milk feeding, weaning period, antibiotic use (external)
Factors that influence the stability of gut microbiota:
enterotypes, BMI, exercise frequency, lifestyle, cultural & dietary habits.
Examples of antimicrobial effects gut microbiota secretes:
SCFAs, secondary bile acids, bacteriocins
Bile acids (primarily are produced by the liver) for digestion of dietary lipids, but can be modified by gut microbiota (secondary bile acids) for their antimicrobial effects:
Bacteriocins are short, toxic peptides produced by bacterial species, their use:
Inhibit colonization & growth of other species.
Bacteriocins mechanism of action:
Disrupt RNA and DNA metabolism
Killing cells (by pore formation in cell membrane)
Indigenous E. coli strain compete with pathogenic E. coli. for amino acids & proline
What is impenetrable and firmly attach to the epithelium:
Inner mucus layer
The composition of microbiota is integral to integrity of mucus barrier:
Yes
How do microorganisms attack pathogenic m. by many competition process:
Nutrient metabolism, pH modification, antimicrobial peptide secretions, effects on cell signalling pathway.
Vitamins gut microbiota can synthesize:
Vitamin K (up to half) & B, biotin, cobalamin, folates, nicotinic acid, pantothenic acid, pyridoxine, riboflavin, & thiamine.
major proportion of the microbially produced vitamins are utilized by other non-vitamin producing bacteria and limits their availability for the host.
True
Microbiome play a role in innate and adaptive immune system training and deve. and immune system regulates it as well:
True
Microbes important for maturation of GALT (mediate immunity & immune oral tolerance)
True
Which microbes induce GALT formation:
Bacteroids subtilis and Bacillus subtilis
Exposure to microbes early in life prevents development of T lymphocytes associated with allergies and inflammatory bowel disease while enhancing helper T-cell repertoire
True
Microbes are required for a full complement of T cells and development of B cells in the mucosa
True
Bacteroides fragilis PSA protects from experimentally induced colitis
True
Bacteroides thetaiotaomicron is vital for induction of angiogenesis in the intestines.
In mice
- In mice, even adults would increase capillarization of intestines with introduction of the bacteria.
What cells are required for capillarization, hint” they secret angiogenin-4.
True
Paneth cells
Gut microbes are necessary for mammalian capillary development
True
Bacteria induce or regulate the expression of many genes in the gut, required for proper development of the gut.
True
Other vertebrates, such as zebrafish also need bacteria to develop their intestines and immune system.
True
Three genes bacteria need to initiate intestinal deve.
Colipase, angiogenin-4, Sprr2a
Microbial symbionts necessary for stem cell division and epithelial cell formation in zebrafish
True
Germ-free mice were leaner and had lower body fat than mice colonised with a conventional microbiota, despite the fact that the latter eat less.
True
When the germ-free mice were colonised with the conventional gut microbiota, they gained weight and showed increased levels (over 50%) of body fat.
Also higher level of leptin (correlate with fat in the body), fasting glucose and insulin within 10-14 days colonialism.
True
Mainly produced by bacteria through fermentation of nondigestible carbohydrates
SCFAs
The three main SCFAs are:
Acetate, propionate, and butyrate
see diagram
acetate, propionate and butyrate exert beneficial effects over intestinal epithelial cells (IECs) and immune cells through
Induction of intracellular or extracellular processes
The SCFA butyrate promotes the epithelial barrier function
True
the main energy source of colonocytes
Butyrate
SCFAs exert anti-inflammatory effects in intestinal mucosa by inhibition of histone deacetylases (HDACs)
TRUE
SCFAs are speculated to play a pivotal role in microbiota-gut-brain crosstalk
True
Symbiotic bacteria may stimulate postnatal development of the mammalian brain.
True
Germ-free mice had lower levels of NGF-1 and BDNF in their brains which correlated with behavioral differences
True
NGF1-A expression in mice depends on symbiotic microbes.
True
Gut bacteria may help regulate anxiety-like behavior and emotional behavior through vagus nerve-dependent regulation of GABA receptors.
True
Gut bacteria is important for normal social behavior in mice. Ex. Germ-free mice were similar to autistic children
True
The bacteria changed the metabolites in the blood, some of which could cause anxiety
True
Some psychological conditions may have a root in the bacterial metabolites
True
Effects of germ-free rearing and germ-free bacterial consortium on social behaviors in male mice
See the diagram
Involvement of the gut microbiota in the modulation of multiple neurochemical pathways through the highly interconnected gut-brain axis.
True
Short-chain fatty acids (SCFAs), the main metabolites produced in the colon by bacterial fermentation of dietary fibers and resistant starch, are speculated to play a key role in neuro-immunoendocrine regulation
Until recently, the intrauterine environment was perceived as sterile
True
However, nonpathogenic bacteria are present in amniotic fluid and placenta (suggesting maternal-fetal exchange of microbes)
Early-life environmental exposures alter the development of the human microbiome. Shifts in the composition of the microbiome are thought to bias maturation of the immune system toward a hypersensitive and/or hyperinflammatory state
True
crucial factor for proper immune development and long-term health
Early-life microbiome
Name microbiome from different places of the body:
Oral microbiome
Gut microbiome
Cervix microbiome
Vagina microbiome
Placenta microbiome
The conventional paradigm is that the placenta is a sterile organ and that adverse pregnancy outcomes are associated with microbes that originate from the reproductive tract (vaginal) and ascend through the cervix to colonize the placenta
The similarity between the oral and placental microbiota suggests that bacteria may pass from the oral cavity to the placenta, possibly explaining the many observations of women with periodontal disease that have an increased risk of pregnancy complications
is a measure of microbiome diversity applicable to a single sample
Alpha diversity
see diagram
is a measure of similarity or dissimilarity oftwo communities
Beta diversity
see diagram
Pregnancy induces a number of immunological, hormonal, and metabolic changes that are necessary for the mother to adapt her body to this new physiological situation
True
These changes alter the mother’s microbiota at different sites such as the gut, the vagina, and the oral cavity. However, published data are not consistent, since a number of factors might influence the microbiota profile such as the diet, antibiotic, or other supplement intakes, as well as the methodology of research
True
The gut microbiota shifts substantially throughout the progression of the pregnancy and is characterized by reduced individual richness (alpha-diversity), and increased inter-subject beta-diversity
Some of the proposed mechanisms by which gut microbiota play a role in host weight gain during pregnancy include
(I) Enhanced absorption of glucose and fatty acids
(II) Increased fasting-induced adipocyte factor secretion
(III)Induction of catabolic pathways
(IV) Stimulation of the immune system
During pregnancy, the microbiome has several roles:
(1)maintenance of a healthy pregnancy,
(2) contribution to fetal development, and
(3) acquisition of necessary bacteria by the neonate for the first days outside the womb.
Prepregnancy obesity and inflammatory bowel disease are associated with gestational dysbiosis, as are several conditions occurring during pregnancy, including gestational diabetes mellitus and preeclampsia
The maternal gut microbiome shifts in composition and function to meet the energetic demand of developing offspring
Maternal exposures, such as diet, stress and infection, may alter maternal gutmicrobiotacomposition, function and availability of microbiota-derived metabolites during pregnancy. In turn, alterations in the availability of microbiota-derived metabolites may exert programmatic effects on the placenta and the fetal compartment
Diet, stress, infection impact maternal microbiota? - then affect maternal microbiome (composition, function, metabolite availability) - then fetal deve. factors (metabolites, growth factors, immune molecules)
True
Stress during the first trimester of pregnancy alters the population of microbes living in a mother’s vagina. Those changes are passed on to newborns during birth and are associated with differences in their gut microbiome as well as their brain development, according to a new study by University of Pennsylvaniaresearchers
Transfer of bacteria from pregnant women to germ-free mice caused different effects depending on the stage of pregnancy.
True
see diagram
There is increasing evidence of the impact of maternal high-fat diet on the offspring microbiome
The maternal diet can alter the immune response and microbiome in the offspring It may be associated with multiple morbidities, including the development of necrotizing enterocolitis, atopy, asthma, metabolic dysfunction, and hypertension
Maternal diet shapes the composition and diversity of breast milk microbiota, with the most important contributions coming from dietary fiber and both plant and animal protein intakes
The amount of gestational fruit and vegetable consumption is associated with distinct changes in the infant gut microbiome at 2 months of age
see diagram
is a major determinant of gut microbiota colonization. The microbiota composition of preterm infants (< 37 weeks) is different than their term counterparts
Birth gestational age
After birth, a rich and dynamic ecosystem develops from mother’s skin, vaginal and fecal microbiota, and environment microbiota contacts. Microbiota colonization varies according to the type of delivery
The profile of intestinal microbiota in the full-term, vaginally delivered, and breastfed infant with healthy and balanced mother’s milk microbiota is considered healthy
another well-known component of human milk favoring gut infant colonization with beneficial bacteria.
Lactoferrin (LF)
See diagram after this
There is a clear compositional distinction between breastfed and formula-fed infants, with breastfed infants being populated with higher proportions of Bifidobacteria and Lactobacillus spp. and formula fed infants being populated with a greater prevalence of clostridiales and proteobacteria
In addition, formula-fed infants exhibit decreased diversity and bacterial richness even after the first year of life (12–24 months of age).
Formula feeding has been associated with an increased risk of various hyperinflammatory and immune-mediated diseases.
The introduction of solid foods and the termination of milk-feeding/weaning coincide with major gut microbiota changes.
See the rest of diagrams
HMO
Human milk oligsccharides
What protections do HMO give newborns:
protect against pathogenic infection
promote development of the intestine
Establish gut microbiota
Stimulate maturation of immune system
See diagram
