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Gut microbiome

The human microbiome has a biomass of approximately 1.5 kg.

The gut microbiome consists of bacteria, archaea, fungi, and viruses.
Bacteria in the microbiome are estimated to be approximately 3.8×10 to the 13th in total.

Trillions of microbial cells inhabit the human body, outnumbering human cells by 10 to one according to some estimates.

The microbiome matures to contain over 100 trillion micro organisms with a high degree of variability between individuals and continues to evolve as one ages.

The gut microbiota has the largest quantity of bacteria and the greatest number of species, compared to other areas of the body.

The gut microbiome is a complex, living entity that starts developing at birth continues throughout adulthood.

The intestines are characterized by a specific microbiome, being colonized by permanent systems of intestinal micro organisms-enterotypes.

The largest number of bacteria reside in the colon, on the surface of the mucous membrane.

The gut microbiome  is involved in metabolism, absorption of nutrients, defense against pathogenic bacteria, plays a key role in development of gut-associated lymphoid tissue, regulation of inflammation, and overall host immunity.

The gut microbiome plays a key role in the development of gut associated lymphoid tissue, regulation of inflammation and overall host immunity.

The digestive tract the most susceptible part of the body to inflammation and disease: most of our immune cells and the microbes that regulate those immune responses live in our digestive tract. 

The gut microbiome affects the immune function, with immune regulatory proteins derived from gut microbes found in distant organs.

The rich array of intestinal microbiota helps process nutrients in food, bolsters the immune system and promotes health.

Commensal intestinal microflora participate in the degradation of nutrients, the growth and differentiation of intestinal epithelium cells, local peristalsis, resistance to colonization by an elimination of pathogens, and also affects the maturation of the immune system

The gut microbiota is considered an organ with the level of complexity comparable to that of any other organ system.

Gut microbiota comprises approximately 3×10 to the 13th bacterial cells and generally exhibit commensalism with the host and are critical to health.

Gut microbiota influences physiological functions, local mucosal homeostasis, inflammation, and immunity.

Its flora can produce a range of neuroactive molecules, such as acetylcholine, catecholamines, γ-aminobutyric acid, histamine, melatonin, and serotonin, which are essential for regulating peristalsis and sensation in the gut.

Alterations of the gut flora composition related to diet, disease, or drugs can change the level of circulating cytokines, some of which can affect the brain.

Biochemical signaling takes place between the gastrointestinal tract and the central nervous system.
The gut microbiome varies between individual parts of the intestine and is an important factor in maintaining the homeostasis of the body.

Excessive macronutrient intake contributes to gut inflammation and perturbation of homeostasis, and micronutrients may also be involved.

The intestine is the largest immune system compartment, it ensures tolerance to foreign antigens, such as food and commensal bacteria.

The microbiome is responsible for creating the right immune cells and cell responses to different threats, maintaining the integrity of the intestinal wall, and producing the right nutrients to maintain homeostasis in the gut. 

The gut is populated with more than 800 species of microbes, the majority of which are excreted in feces, and a number of which are well equipped to be pathogenic.

Has a role in the pathophysiology of obesity by influencing the host energy metabolism, adiposity, neuroendocrine signaling, and insulin sensitivity.

The same meal can have a variable effect on blood glucose in different nondiabetic individuals depending, in part, on the make up of the gut microbiota.

A diminished microbial ecosystem affects allergies and inflammation, metabolic diseases like diabetes and obesity, and even mental health conditions like depression and anxiety.

After only 10 days of treatment with systemic antibiotics, the gut microbiota can be altered for up to 1 year.

Inappropriate antibiotic exposure may be linked to an increased risk of colon cancer by alterations in the microbiome.

Probiotic based fecal microbiota transplantation has improved the prognosis in certain cancer patients.

Some live bacterial species play key roles in cancer remediation, influence anti-inflammatory cytokine levels, detect and degrade potential carcinogens, and activate phagocytes for eliminating early stage cancer cells.

90% of the bacteria inhabiting the intestine are from the Bacteroidetes and Firmicutes phyla. 

Bifidobacterium and Lactobacillus are associated with reduced incidence of cancer and are known to induce other health benefits as well as their immunomodulation roles.

Dysbiosis and loss of microbial diversity during a hematopoetic stem cell transplant, correlates with shortened survival and higher transplant related mortality rate and high degree of graft versus host disease.

Cancer therapy may affect the gut microbiome.

The gut flora is established at one to two years after birth.

By 1-2 years the intestinal epithelium and the intestinal mucosal barrier that it secretes have co-developed in a way that is tolerant to, and even supportive of, the gut flora and that also provides a barrier to pathogenic organisms.

Higher gut microbial diversity is associated with improved survival in patients undergoing hematopoeticpoetic stem cell transplantation:microbiome health is associated with transplant related mortality, acute, graft versus host disease, and graft versus host disease lethality.

Dysbiosis of the microbiome is more pronounced among patients with gut graft versus host disease compared with patients who did not have graft vs. host disease.

Patients with hematologic malignancies, are at  increased risk for injury to the microbiome, owing to exposure to chemotherapy that may cause mucositis and prevent patients from eating, and the use of broad-spectrum antibiotics that affects gut microbiota commensals.

Much of the composition of the microbiome is established early in life, influenced by genetics and whether you were breast-fed or bottle-fed.

Microbial diversity is undermined by the American diet, rich in sugar, meats and processed foods.

A diet containing a variety of plant-based foods may be crucial to achieving a healthier microbiome.

The ecosystem in the gut determines how it absorbs and processes nutrients.

Alterations in the intestinal microbiota may influence NAFLD increase the permeability of intestinal tissue, facilitating increased liver exposure to harmful substances such as translocated bacteria, bacterial toxins, and inflammatory chemical signals.

The nutritional value of food is influenced in part by the microbial community that encounters that food.

Calorie-restricted patients have a richer and more diverse microbial community in the gut than those eating a typical American diet.

Calorie-restricted patients carry several strains bacteria that promote health, unique to a plant-based diet.

Diet alterations can induce persistent changes in a gut microbial community.

Microbiota may also play a role as Enterobacteriaceae was found in significantly high levels in patients with diverticular disease.

Depletion of Clostridium cluster IV, Clostridium cluster IX, Fusobacterium, and Lactobacillaceae are found in patients with symptomatic diverticula disease.

When the intestinal ecology is altered, commensal bacteria such as Clostridium difficile and vancomycin resistant enterococcus may expand and become pathogenic and exert pathobiologic effects.

Chemotherapy can lead to altered gut micribiome and promote CDI even in the absence of antibiotic drug exposure.

Spouses who live together will develop microbial communities that are similar to each other.

Dysbiosis of gut microbiome with loss of microbial diversity, expansion of enteropathogens, and altered vitamin B12 biosynthesis is correlated with biological age rather than chronological age.

To improve the micrbiotome, a plant-based diet high in fiber is recommended.

Such a diet provides genetic diversity, healthier species and fewer pathogenic bacteria living in the gut

Patients with a high microbiota metabotype have an elevated risk for irinotecan dependent adverse drug responses.

PD-1 inhibitor responses in melanoma are related to gut microbiome, with response rate much higher in patients with a diversity of of bacteria in their gut and a different composition of gut bacteria with more Faecalibacterium, Ruminococcacaceae and Clostridiales.

Patients with melanoma treated with PD-1 inhibitors and who failed to respond to therapy had a higher level of Bacteroides.

There is a relationship between the gut microbiota and antibiotics, and the response to checkpoint inhibitors: antibiotics delivered before treatment may diminish benefits in response rates and duration of responses.

Certain species of bacteria enhance the effects of checkpoint inhibitors, and can increase activation of T cells.

Gut  microorganisms benefit the host by collecting the energy from the fermentation of undigested carbohydrates and the subsequent absorption of short-chain fatty acids (SCFAs), acetate, butyrate, and propionate.

 

Intestinal bacteria help synthesize vitamin B and vitamin K as well as metabolizing bile acids, sterols, and xenobiotics.

The short chain fatty acids absorbed, and other compounds they produce are like hormones suggest the gut flora itself appears to function like an endocrine organ.

 

The dysregulation of the gut flora is correlated with a host of inflammatory and autoimmune conditions.

 

The microbial content of the gut in healthy people consists of 2 basic groups: Firmicutes and Bacteroidetes which represent approximately 90% of the micro organisms.
Microbiome can cooperate with the host, support the body, contribute to the development and progression of disease.

The bacterial density increases with a positive gradient from the proximal tract to the distal.

The gastrointestinal tract is sensitive to emotion. 

Stress, depression or other psychological factors can affect movement and contractions of the GI tract.

Many people with functional GI disorders perceive pain more acutely than other people do because their brains are more responsive to pain signals from the GI tract.

 

Stress can make the existing pain seem worse.

 

Psychologically based approaches lead to greater improvement in digestive symptoms compared with only conventional medical treatment.

 

Emotional and psychosocial factors play a role in functional gastrointestinal disorders.

 

Emotions cause genuine chemical and physical responses in the body that can result in pain and discomfort.

 

The colonic microbiota ecosystem acts symbiotically with the host to sculpt a robust immune response.

 

Commensal bacteria and their products have an essential role in the normal development and functioning of the immune system. 

 

When the integrity of the mucosal barrier is compromised, normally innocuous commensal bacteria can become pathogenic by crossing the epithelium and eliciting an immune response and intestinal inflammation.

When the balance of bacteria in the gut becomes disrupted, a less verse, less stable, and often more pathogenic microbiota result, contributing to various disease pathologies by negatively influencing  either host metabolism oh host immune responses and functions.

Dysbiosis of the gut microbiome is associated with tumorigenesis.

The presence of commensal bacteria interferes with the ability of pathogens to colonize and invade the gut, in part because of competition for space and nutrients. 

 

The bacterial communities colonizing the human body play essential roles in the development of host immunity, metabolism, and behavior.

 

There are qualitative and quantitative differences of commensal bacteria between the right and left colon cancers, which induce epigenetic changes in the intestinal epithelial cells and the the resident immune population.

 

Studies  have shown an association between antibiotic use and an increased risk for colon cancer.

There are three primary ways by which bacteria fwdoster the initiation and progression of tumor formation: secretion of microbial products, inducing toxic molecules and reactive oxidative stress, direct contact and interaction with host cells through attachment, invasion and translocation and modification of the host genome and signaling pathway.

A Swedish population study from more than 40,000 colorectal cancer patients and 200,000 cancer-free control persons, found that moderate use of antibitotics increased the risk for proximal colon cancer by 9% and that very high antibiotic use increased the risk by 17%.

 

Innate immune cells, which express invariant receptors that detect microbial products or patterns, include granulocytes, macrophages, and dendritic cells.

 

Adaptive immune cells include B cells and T cells, which express highly variable receptors that recognize specific antigens, and mucosal-associated invariant T cells, which express antigen receptors with more limited diversity. 

 

The mucosal immune system represents the largest component of the immune system, containing approximately 75% of all lymphocytes and producing the majority of immunoglobulin in healthy persons.

 

The mucosal immunity must simultaneously balance the opposing demands of providing protective immunity against pathogens while preventing excessive immune responses against innocuous food antigens and commensal microbes.

 

There is a close interreaction between host gut microbiome, tumor genome, and tumor immune microenvironment.

 

Gut microbiota and oral probiotics have been found to influence systemic inflammation, oxidative stress, glycemic control, tissue lipid content, and mood.

 

Gut flora can produce noradrenalin, and serotonin, that might affect anxiety.

 

There is a link between the gut microbiome, mood disorders and anxiety, and sleep. 

 

The microbiome changes depending on the time of day, meaning that throughout the day, the gut is exposed to varying metabolites produced by the microbes active during that time. 

 

Microbial changes are associated with differences in the transcription of circadian clock genes involved in circadian rhythm. 

 

Stress and sleep disturbances can lead to greater gut mucosal permeability via activation of the HPA axis, and  this causes immune inflammatory responses that contribute to the development of illnesses that cause depression and anxiety.

 

Around 70% of people with autism also have gastrointestinal problems, and autism is often diagnosed at the time that the gut flora becomes established, indicating that there may be a connection between autism and gut flora.

 

Colorectal cancer there is a relative abundance of species in metabolites that differ from the healthy bowel: and enriched bacteria in fecal samples for patients with colorectal cancer is most consistently is Fusobacterium nucleatum.

Diet influences the composition of the gut microbiome,  and a western diet and obesity can lead to gut dysbiosis and chronic intestinal inflammation, which can promote colorectal tumorigenesis.

Microbiota dysbiosis, or an imbalance in gut microbes, can stimulate food intake and contribute to weight gain and development of obesity.

A Western style diet is associated with excess sulfur metabolizing bacteria in feces,and is associated with an increased risk of colorectal cancer.

Antibiotics substantially alter the gut microbiome and prolonged use may be a risk factor for early onset colorectal cancer.

In obese people, the relative proportion of Gram-positive bacteria in gut microbiota is increased resulting in greater conversion of the non-genotoxic primary bile acid, cholic acid, to carcinogenic deoxycholate.

 

Fusobacterium nucleatum levels are correlated with microsatellite instability and poor prognosis.

 

Anger, anxiety, sadness, elation and other feelings can trigger symptoms in the gut.

 

 

The brain has a direct effect on the stomach and intestines: the thought of eating can release the stomach’s juices before food gets there. 

This connection goes both ways: a troubled intestine can send signals to the brain, just as a troubled brain can send signals to the gut. 

A stomach or intestinal distress can be the cause or the product of anxiety, stress, or depression. 

The gut-brain axis includes: the CNS, neuroendocrine and neuroimmune systems, including the hypothalamic-pituitary-adrenal axis (HPA axis), sympathetic and parasympathetic arms of the autonomic nervous system, including the enteric nervous system and the vagus nerve, and the gut microbiota.

The gut flora is established at one to two years after birth.

Gut microorganisms benefit the host by collecting the energy from the fermentation of undigested carbohydrates and the subsequent absorption of short-chain fatty acids, acetate, butyrate, and propionate.

Intestinal bacteria play a role in synthesizing vitamin B and vitamin K as well as metabolizing bile acids, and sterols.

Gut microbes produce essential components such as vitamin K, an important cofactor in blood clotting, and short-chain fatty acids, an energy source for colonic epithelial cells. 

The gut flora itself appears to function like an endocrine organ.

Dysregulation of the gut flora has been correlated with a host of inflammatory and autoimmune conditions.

Malnutrition in children is associated with defects in gut microbiome with microbial communities that appear to be younger than those of their healthy counterparts.

Children with a higher ratio of Firmicutes to Bacteroidetes will absorb more calories and be more likely to gain weight.

The composition of microorganisms in the gut can affect nutrient absorption and energy regulation, thus influencing the development of obesity.

The gut flora composition changes over time, when the diet changes, and as overall health changes.

Indole is produced from tryptophan by various bacteria.

Indole and subsequently 3-indolepropionic acid (IPA),is a highly potent neuroprotective antioxidant that scavenges hydroxyl radicals.

IPA promotes a neuroprotective effect against cerebral ischemia and Alzheimer�s disease.

Lactobacillus species metabolize tryptophan into metabolites that act on intestinal immune cells, resulting in increased interleukin-22 production.

Indole itself triggers the secretion of glucagon-like peptide-1 (GLP-1) in intestinal cells.

Indole can also be metabolized by the liver into indoxyl sulfate, a compound that is toxic in high concentrations and associated with vascular disease and renal dysfunction.

Activated charcoal. an oral intestinal sorbent, adsorbs indole, in turn decreasing the concentration of indoxyl sulfate in blood plasma.

The enteric nervous system is one of the main divisions of the nervous system.

The enteric nervous system consists of a system of neurons that governs the function of the gastrointestinal system.

As the enteric nervous system can operate autonomously and normally communicates with the CNS through the parasympathetic and sympathetic nervous systems.

Communication occurs between the gastrointestinal system and the parasympathetic system via the vagus nerve.

Communication occurs between the gastrointestinal system and the sympathetic nervous system via the prevertebral ganglia.

The enteric nervous system includes efferent neurons, afferent neurons, and interneurons.

The enteric nervous system capable of carrying reflexes in the absence of CNS input.

The sensory neurons of the enteric nervous system can report on mechanical and chemical conditions in the G.I. tract.

The motor neurons in the enteric nervous system control muscle peristalsis and churning of intestinal contents.

Other neurons of the enteric nervous system control the secretion of enzymes.

The enteric nervous system uses more than 30 neurotransmitters.

These enteric nervous system neurotransmitter, are mostly identical to the ones found in CNS, such as acetylcholine, dopamine, and serotonin.

More than 90% of the body’s serotonin lies in the gut.

About 50% of the body’s dopamine resides in the gut.

The gut-brain interaction is demonstrated between the sight and smell of food and the release of gastric secretions, known as the cephalic phase, or cephalic response of digestion.

This gut-brain axis, is a bidirectional neurohumoral communication system.

The gut-brain axis is important for maintaining homeostasis and is regulated through the central and enteric nervous systems via its neural, endocrine, immune, metabolic, hypothalamic-pituitary-adrenal axis, and the microbiome-gut-brain axis pathways.

The intestinal flora can produce neuroactive molecules, such as acetylcholine, catecholamines, ?-aminobutyric acid, histamine, melatonin, and serotonin, which are essential for regulating peristalsis and sensation in the gut.

Alterations of the gut flora composition related to diet, disease, or drugs can change the level of circulating cytokines, some of which can affect the brain.

Gut flora release substances that can activate the vagus nerve, which transmits information about the state of the intestines to the brain.

Activation of the hypothalamus-pituitary-adrenal axis by stress causes gut flora changes, as well as intestinal epithelial alterations with probable systemic effects.

The cholinergic anti-inflammatory pathway, signaling through the vagus nerve, affects the gut epithelium and flora.

IBD accelerates hypermethylation, chromosomal and microsatellite instabilities, and quantitative and qualitative changes in the intestinal microbiome.
Intestinal dysfunction causes the loss of intestinal epithelial barrier function, contributing to increased severity of IBD mainly within the colon, and as a result to the development of colorectal cancer.

Crohn’s disease and ulcerative colitis are associated with reduced total number, and diversity of microbial species. 

Hunger and satiety are integrated in the brain.

The gut microbiome  has both oncogenic and tumor suppressive activity.
Several carcinogenic microbes are associated with oncogenesis through signaling pathways they promote direct double-stranded DNA damage, increased reactive oxygen species, and amplification of nuclear Kappa-like chain enhancer of activated B cell signaling.
Toxins released by bacterial pathogens possess DNAase activity that contributes to genomic instability that ultimate leads to tumor formation and progression.
Conversely the gut microbiome provides competition that selects against carcinogenic pathogens reducing the ability of these pathogens to populate a host.
Pathogenic bacteria such as Shigella and Bacteroides species could lead to accumulation of DNA damage and genomic variations by host DNA damage response interference or oxidative stress generation.
Certain bacterial species can assist cancer genesis by inhibiting host antitumor immune responses as in the case of Fusobacterium nucleatum that arrest the ability of NK cells to attack tumor cells.
Gut bacteria are associated with gastric, colorectal, and biliary cancers, and speculation exists for the development of breast cancers and brain tumors causing changes in phytoestrogens and estrogen‘s and altering the gut brain access.

The presence or absence of food in the gut and types of food present affect the composition and activity of gut flora.

Strains of probiotic bacteria found that certain species of the Bifidobacterium and Lactobacillus genera have potential to be useful for certain central nervous system disorders.

Around 70% of people with autism also have gastrointestinal problems, and autism is often diagnosed at the time that the gut flora becomes established.

The gastrointestinal tract is sensitive to emotion, as anger, anxiety, sadness, elation can trigger symptoms in the gut.

The brain has a direct effect on the stomach and intestines, and vice versa.

A person may experience gastrointestinal upset with no obvious physical cause: functional GI disorders.

Psychosocial factors influence the actual physiology of the gut, as well as symptoms.

Some people with functional GI disorders perceive pain more acutely than other people do because their brains are more responsive to pain signals from the GI tract.

Stress can make the existing pain seem even worse.

Some patients with functional GI conditions might improve with therapy to reduce stress or treat anxiety or depression.

Patients who try psychologically based approaches had greater improvement in their digestive symptoms compared with patients who received only conventional medical treatment.

Signs of stress:

Stiff or tense muscles, especially in the neck and shoulders

Headaches

Sleep problems

Shakiness or tremors

Recent loss of interest in sex

Weight loss or gain

Restlessness

Behavioral symptoms

Procrastination

Grinding teeth

Difficulty completing work assignments

Changes in the amount of alcohol or food consumed

Taking up smoking, or smoking more than usual

Increased desire to be with or withdraw from others

Rumination

Emotional symptoms

Crying

Overwhelming sense of tension or pressure

Trouble relaxing

Nervousness

Quick temper

Depression

Poor concentration

Trouble remembering things

Loss of sense of humor

Indecisiveness

Emotions cause genuine chemical and physical responses in the body that can result in pain and discomfort.

The microbiome can promote or inhibit the anti-cancer effects of chemotherapy agents and immunotherapy.

Bacterial enzymes have conferred resistance through induction of autophagy.

Evidence exists that the gut microbiome affects the development of cardiovascular disease, and heart failure in particular.

Excessive consumption of alcohol increases the permeability of tight intestinal epithelial junctions, and indices profound changes in the microbiome, including increasing increased pathogenic bacteria.

Elevated levels of phenylacetylglutamine (PAG), a byproduct created when microbes in the gut break down dietary protein, is linked to increased heart failure risk and severity. 

Studies show linked increased PAG levels to a higher risk of myocardial infarction (MI), stroke, and death.

A microbiome that is predisposed towards making PAG is at higher risk of cardiovascular disease, especially heart failure.

Excessive alcohol consumption increases gut permeability, and disrupts intestinal epithelial cell junctions and induces profound changes in the microbiome, including increased pathological bacteria.

 

 

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