Link between gut and type 1 diabetes

Scientists have found that targeting micro-organisms in the gut, known as microbiota, could have the potential to prevent type 1 diabetes. University of Queensland researcher Dr. Emma Hamilton-Williams investigated differences in the gut microbiota, comparing those susceptible to type 1diabetes to those protected against the autoimmune disease.

This research has shown there is a genetic component to microbiota and the immune response involved in regulating it, this means that changes in the microbiota in type 1 diabetes occur before symptoms develop, and are not just a side-effect of the disease. Therapies targeting the microbiota could therefore have the potential to help prevent type 1 diabetes in the future.

An immunotherapy targeting T-cells associated with type 1 diabetes resulted in dramatic changes in the gut biology and altered the microbiota in mice models. Genetic susceptibility and change in immune system function led to alterations in the microbiota. The implications are that a person's genetics contribute to an unhealthy microbiota as well as their diet.
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Effects of circadian rhythms on autoimmune disease

Circadian rhythms are generated by the body clock, allowing human to anticipate and respond to the 24-hour cycle of the planet. Maintaining a good body clock is generally believed to lead to good health for humans, and disrupting the circadian rhythm-or example, working night shifts has been associated with immune diseases such as multiple sclerosis; however, the underlying molecular links have been unclear.

Immune responses and regulation of autoimmunity are affected by the time of the day when the immune response is activated. Using mice as a model organism, they show that a master circadian gene, BMAL1, is responsible for sensing and acting on time-of-the-day cues to suppress inflammation.

Loss of BMAL1, or induction of autoimmunity at midday instead of midnight, causes more severe experimental autoimmune encephalomyelitis, which is essentially an analogue of multiple sclerosis in mice. Immune system is programmed to respond better to infection and insults encountered at different immune in the 24-hour clock.

This has significant implications for the treatment of immune-mediated diseases and suggests there may be important differences in time of day response to drugs used to treat autoimmune diseases such as multiple sclerosis. Disruption of human body clocks, which is quite common now given our 24/7 lifestyle and erratic eating and sleeping patterns, may have an impact on autoimmune conditions.
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Lupus increases the risk of dementia

Lupus is a chronic autoimmune disease that causes the body to attack its own healthy cells. It is thought to be caused by genetic and environmental factors. Environmental factors can trigger attacks or 'flare ups. 'Flare ups vary from person to person and are not the same each time. They can be marked by fatigue that can be mild or debilitating. Fatigue is often an early indicator that an attack is about to set in.

Attacks can cause joint and muscle pain and swelling, particularly at the wrists, hands, elbows, knees and ankles. Many people with lupus experience skin problems. The most distinctive marker of lupus is a butterfly-shaped rash on the face. Lupus may also cause light sensitivity, fever, changes in weight and swollen glands. People with lupus sometimes complain of a 'fog,' that can feel like depression or anxiety and sometimes causes them to have difficulty focusing and expressing themselves.

It causes the body’s immune system to break cells in parts of the body including the kidneys, lungs, skin and blood vessels. Lupus may impair memory and cognitive functions. Researchers analyzed data from more than 7,000 people and found that dementia was far more common among people with dementia than those without the disease. Lupus is best known for the damage it does to the kidneys, but its symptoms can be extremely varied, making it very difficult to diagnose.

Experts have identified numerous forms of the disease, including nineteen variations of neuropsychiatric lupus, which affects the central nervous system, including cognitive and memory functions and can even cause psychological and psychiatric symptoms. Some patients refer to a ‘lupus fog,’ a catchall description of the experience of difficulty concentrating, remembering facts, and expressing oneself.

The fog can also come with depression and anxiety, all of which may signal a lupus flare up. Patients who do not have a neuropsychiatric form of lupus are at a greater risk of dementia. Steroids are also associated with memory loss and cognitive impairment in lupus patients.
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New disease responsible for kidney failure

Reserchers have discovered an insidious new autoimmune disease that causes kidney failure. Anti-brush border antibody ABBA disease. Researchers identified ABBA after analyzing biopsied kidney tissue from different patients who had developed acute kidney injury, a sudden episode of kidney failure or damage that happens within a few hours or days.

The condition causes a build-up of waste products in the blood and makes it difficult for kidneys to maintain adequate balance of fluid in the body.
Researchers discovered that in the nephrons, the functional units of the kidneys, antibodies had coated a specialized part of cells called brush borders, which help reabsorb and process proteins.

Since it is an autoimmune disease, different approaches to suppress the immune system were used to treat the patients, but those efforts were unsuccessful, determining where on the protein megalin - which acts as a sponge to absorb proteins and other compounds that enter the nephron - the antibody binds is very important for key to treating the disease.
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Aging leads to an imbalance in gut bacteria

According to a new study in PLOS Pathogens, different changes to the microbial community of the stomach may be the reason why conditions are associated with different risk levels and types of gastric tumor. Autoimmune disease or infection with Helicobacter pylori bacteria can damage the stomach and reduce gastric acid secretion.

Despite their similar effects, each of these conditions is associated with higher risk of a different type of gastric tumor. Meanwhile, widely used medications known as proton pump inhibitors PPIs also reduce gastric acid secretion, but they do not increase cancer risk. Elderly people tend to have different gut bacteria profiles from younger people.

This new research suggests that this change in balance is linked to inflammaging, which is related to most late-onset diseases and disorders. Inflammaging is a catch-all term for the tendency of elderly people to have generalized inflammation. It is thought to be related to evolved changes that the immune system undergoes as a person gets older.

It isn’t clear whether aging causes inflammation or inflammation causes aging, but the two go hand-in-hand, and susceptibility to many diseases goes along with both of them. Researchers took samples from older mice – whose gut bacteria composition, like humans’, changes with age – and introduced them to the bodies of younger mice. After the procedure, the younger mice developed chronic inflammation, like the inflammaging that would normally have struck them later in life.

They also transplanted gut bacteria from one group of younger mice to another group of mice of around the same ages to see if the immune response was just to the introduction of foreign bacteria. The mice with transplanted gut bacteria from older ones developed inflammaging.

The differences in the responses suggested to the researchers that aging leads to an imbalance in gut bacteria, such that there are more ‘bad’ bacteria than good in the microbiome. The proliferation of the bad bacteria leaves the gut lining more permeable to toxins that can contaminate the bloodstream and lead to disorders like inflammatory bowel disease, obesity, diabetes, anxiety, autism and cancer.
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Activation of immune T cells changes behavior

Researchers have discovered that T cells immune cells that protect the body from infections and cancer change the body's metabolism when they are activated, and that this activation leads to changes in behavior.

It is currently known that individual T cells change their metabolism to meet their energy needs after being activated, but the systemic metabolic effect of sustained activation of the immune system has remained unexplored.

 To understand the systemic effects, the group looked at T cell activation in mice designed to lack a surface receptor called PD-1, which is necessary for inhibiting the activity of T cells. T cells remain activated in mice without the receptor, similar to those in the immune systems of people with certain types of autoimmune disease.

In these mice, they found that amino acids molecules that are used to build proteins were depleted in the blood, and that they were increased in the T cells themselves, implicating the T cells in the change. The team tracked and imaged amino acids in many organs, and found that the depletion of amino acids from the blood was taking place due to the accumulation of amino acids in activated T cells in the lymph nodes, showing that strong or long lasting immune responses can cause metabolic changes elsewhere in the body.

Researchers analyzed the biochemistry of the brain, they found that the systemic decrease in the amino acids tryptophan and tyrosine in blood led to lower amounts available in the brain, limiting production of the neurotransmitters serotonin and dopamine. These neurotransmitters affect emotions, motivation and fear.

Serotonin is often a target of drugs that combat depression. The researchers found that their depletion in mice without PD-1 resulted in behavioral changes dominated by anxiety and exacerbated fear responses, which could be remedied by providing a diet rich in an essential amino acid.
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Celiac disease after diabetes

Type 1 diabetes and celiac disease are closely related genetically, People with one disease tend to get the other. People who have type 1 diabetes autoantibodies should get screened for celiac autoantibodies. Type 1 diabetes is an autoimmune disease that causes the body's immune system to mistakenly attack the insulin-producing cells in the pancreas, insulin is a hormone that sends the sugar from foods into the body's cells to be used as fuel. Because the autoimmune attack leaves people with type 1 diabetes without enough insulin, they must replace the lost insulin through injections or an insulin pump with a temporary tube inserted under the skin.

Celiac disease is an autoimmune disease that causes the immune system to attack the lining of the small intestine when gluten is consumed, according to the Celiac Disease Foundation. Gluten is a protein found in wheat. Symptoms of celiac disease include stomach pain, bloating, diarrhea, vomiting, constipation, weight loss, fatigue, delayed growth and puberty.

Early diagnosis of celiac disease is important to initiate treatment with a gluten-free diet to prevent complications, particularly growth retardation in children. Other complications are iron-deficiency anemia, osteoporosis, skin rash lymphoma and carcinoma of the small intestine. Treatment for the disease is avoiding eating or drinking anything containing gluten.

The researchers carried out autoantibody test on many children and follow them up for 66 months. Autoantibodies linked to type 1 diabetes were found in some of the children while some have autoantibodies linked to celiac disease. Some of the children have both, the results showed the link between the two diseases, type 1 diabetes mellitus is a risk factor for the development of celiac disease.
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New blood cell indicates autoimmunity

Sjögren syndrome is an autoimmune disease that affects the mucous membranes and moisture-secreting glands of the eyes and mouth. Other symptoms are- dry skin, a chronic cough, vaginal dryness, numbness in the arms and legs, fatigue, muscle and joint pains and thyroid problems.

Patients with these syndrome have a significant increase in T follicular regulatory cells Tfr. These cells are usually found in lymphoid tissues, where they regulate antibody production.

 Their is an increase of this type of cell in patients with excessive antibody production. Researchers compared Tfr cells in the blood and in the tissues where antibodies are produced (tonsils obtained from pediatric tonsillectomies), provided evidence that blood Tfr cells are immature, not able to fully suppress antibody production.

Such immaturity was confirmed by studying blood samples from other patients with genetic defects. Exposure of healthy volunteers to flu vaccine led to an increase in blood Tfr cells, in line with their generation during immune responses with antibody production.

Blood circulating Tfr cells are distinguished from other circulating lymphocytes by two molecular markers, CXCR5 and FOXP3, the first of which endows these cells with the ability to migrate into specific zones of lymph nodes, where they may complete maturation and regulate antibody production.
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How to rearrange immune system cells

Immune system imbalanced due to overly-active cells or cells that suppress its function can cause different diseases. Manipulating the function of  T cells, could restore the immune system's balance and create new treatments for any diseases.

Pro-inflammatory cells that boost the immune system can be rearrange into anti-inflammatory cells that suppress disease. Effector T cells activate the immune system to defend human body against different pathogens while regulatory T cells control the immune system and prevent it from attacking healthy parts of its cells.

This rearrangement can be used in the treatment of autoimmune diseases and immuno-oncology therapies. The use of molecule drug that can rearrange effector T cells into regulatory T cells is very important for strengthening  immune systems. This metabolic mechanism changes one cell type into another.

In autoimmune disease, effector T cells are activated and cause damage to the body. Changing these cells into regulatory T cells could reduce the hyperactivity and return balance to the immune system. This rearrangement could improve therapies using stem cells, promotes immune tolerance and prevents the body from rejecting newly-transplanted cells.

Some cancers control regulatory T cells to suppress the immune system and allowing tumors to grow without detection. This process can activate the immune system, recognize cancer cells and attack them.
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Links between diabetes and prednisone

Prednisone is a steroid, steroids are used to treat different conditions like autoimmune disorder and inflammation.

Steroids reduce the activity of the body's immune system and inflammation, it can also prevents tissue damage and how the body reacts to insulin.

Diabetes is a metabolic condition of having higher than normal blood sugar levels.

Type 1-damage pancreatic cells; when pancreas cannot produce insulin.
Types2-when pancreas cannot produce enough insulin.

Steroid-induced diabetes is similar to type 2 diabetes, risk of developing steroid-induced type 2 diabetes are: being overweight, having impaired glucose tolerance, having family history of type 2 diabetes.