Volvulus of Midgut

New research has found a better education has a strong genetic correlation and a protective causal association with several gut disorders. We've long known education is important for many aspects of life, but now a new benefit has been discovered: it can look after your gut health. Landmark Edith Cowan University (ECU) research has found a better education has a strong genetic correlation and a protective causal association with several gut disorders. A previous study from ECU's Centre for Precision Health (CPH) discovered a genetic link between gut health and Alzheimer's Disease (AD) but couldn't conclude whether one caused the other. This study breaks new ground by finding that a higher level of education protects against gut disorders. CPH Director and study supervisor Professor Simon Laws said these findings build upon the centre's previous work to provide further evidence of the strong links between the brain and gut, known as the gut-brain axis. "Gut disorders and Alzheimer's may not only share a common genetic predisposition but may be similarly influenced by genetic variations underpinning educational attainment," Professor Laws said. This large-scale study examined the genetic information of more than 766,000 individuals, with an emphasis on AD, cognitive traits and gut disorders, including peptic ulcer disease (PUD), gastritis-duodenitis, gastroesophageal reflux disease (GERD), irritable bowel syndrome, diverticulosis and inflammatory bowel disease (IBD). It found higher levels of education and cognitive functioning reduced the risk of gut disorders. Lead researcher Dr Emmanuel Adewuyi said the findings have significant implications. "The results support education as a possible avenue for reducing the risk of gut disorders by, for example, encouraging higher educational attainment or a possible increase in the length of schooling," he said. "Hence, policy efforts aimed at increasing educational attainment or cognitive training may contribute to a higher level of intelligence, which could lead to better health outcomes including a reduced risk of gut disorders." It goes both ways ECU's study further revealed the gut may also influence the brain. GERD showed evidence of causing a decline in cognitive function across a number of cognitive traits assessed in the study, such as intelligence, cognitive performance, educational attainment and educational qualification. Although this is the first study to report this finding, the results support recent research reporting an increased incidence of dementia and GERD, which Dr Adewuyi said could help with earlier diagnoses and potential treatments. "GERD may be a risk factor for cognitive impairment, so it's important for health workers to look for signs or symptoms of cognitive dysfunction in patients presenting with the gut disorder," he said. "This could lead to earlier detection of cognitive decline and therefore earlier interventions aimed at reducing the rate of cognitive decline. "More studies are needed to investigate whether treatment for, cure or remission of GERD can contribute to a reduced risk of cognitive decline." The curious case of IBD Interestingly, higher levels of education and cognitive function protecting against gut disorders was true of all the disorders examined in the study -- but largely with the exception of inflammatory bowel disease. Further analysis reveals different effects of IBD on cognitive traits and AD at different genomic locations, indicating its relationship depend on effects at specific locations across the genome. This new understanding may explain the lack of significant genetic correlation of IBD with cognitive traits and AD, and the inconsistency reported in previous observational studies. Dr Adewuyi said this finding was also important, as it brings a new insight into the relationship of IBD with cognitive traits (and AD), which may shape the direction of future studies. "For example, some risk genes for AD may be protective against IBD, and vice versa," he said. 'Relationship of cognition and Alzheimer's disease with gastrointestinal tract disorders: a large-scale genetic overlap and Mendelian randomisation analysis' was published in the International Journal of Molecular Sciences.

A new paper looks outside this brain region and reviews the various brain pathways that meet in the brain stem to control feeding behavior, using a technique that offers an unbiased look at the neurons involved, which could offer targets for better obesity drugs. Every meal you sit-down-to makes an impression, with foods filed away as something delicious to be sought out again, or to be avoided in disgust if we associate the flavor with gut malaise. How this decision is made turns out to be so fundamental to our wellbeing -- determining what foods to seek and avoid -- that the signals are coordinated within the most primitive parts of our brains, the brain stem or hindbrain. This brain region also helps us decide when we are "full" and should stop eating. To date, scientists interested in how and why people gain weight and the diseases that can result from overeating and obesity have focused on a part of the brain called the hypothalamus, following discoveries of two intertwined systems that play important roles in controlling energy balance, the leptin and melanocortin systems. A paper in the journal Nature Metabolism looks outside this brain region and reviews the various brain pathways that meet in the brain stem to control feeding behavior, using a technique that offers an unbiased look at the neurons involved. "Everything the hypothalamus does ends up converging in the brainstem. The brain stem is super important in the control of feeding because it takes all sorts of information from your gut, including whether the stomach is distended and whether nutrients have been ingested, and integrates this with information from the hypothalamus about nutritional needs before passing it all on to the rhythmic pattern generators that control food intake," said Martin Myers, Jr., M.D., Ph.D., professor of internal medicine and Molecular & Integrative Physiology and director of the Elizabeth Weiser Caswell Diabetes Institute. The recent review builds on recent findings in mice from the Myers lab that revealed the existence of two different food intake-suppressing brain stem circuits- one that causes nausea and disgust, and one that does not, as well as from collaborations with colleague Tune Pers, Ph.D., of the University of Copenhagen. Pers and his group used single cell mapping of brain cells within the dorsal vagal complex, a region in the brain stem that mediates a host of unconscious processes, including feelings of satiety (or sickness) after eating. The new review paper, from first author Wenwen Cheng, Ph.D., Myers, Pers, and their colleagues, integrates these findings with other recent discoveries to build a new model of brainstem neuronal circuits and how they control food intake and nausea. "Taking all of this information together allows us to predict which set of neurons control this or that function," said Myers. He notes that many of these cell populations are targets for new and effective anti-obesity drugs -- for example, a class of drugs for diabetes called GLP1 receptor agonists that can lower blood sugar and help you eat less. "There is a population of GLP1 neurons in the brain stem which, if you turn them on, will stop food intake but cause violent illness, but there may be another population of neurons that stops eating without making you feel badly." Having a detailed map of these neurons and understanding the effects of modifying these cell targets, Myers explains, can assist in making drugs with fewer negative side effects.

Alzheimer’s disease (AD) is not totally understood. The abnormal accumulation of proteins in the brain, such as beta-amyloid and tau, is involved with the disease, as is neuroinflammation. But other factors are also associated with this disease, including gut disorders. For that and more research news, continue reading. A Link Between Gut Disorders and Alzheimer’s Disease People with certain disorders of the gut may be at greater risk of developing Alzheimer’s disease, and a study from Edith Cowan University confirmed the association. The latest research analyzed large genetic data sets from AD and several gut-disorder studies of approximately 400,000 people. Their analysis found that people with AD and gut disorders have genes in common. Although the study didn’t conclude that gut disorders cause AD or vice versa, they do support the concept of the so-called “gut-brain” axis, a two-way relationship between the brain’s cognitive and emotional centers and the functioning of the intestines. The research was published in the journal Communications Biology. In addition, they found that abnormal cholesterol levels were a risk for both AD and gut disorders. “Looking at the genetic and biological characteristics common to AD and these gut disorders suggests a strong role for lipids metabolism, the immune system, and cholesterol-lowering medications,” Emmanuel Adewuyi, Ph.D., research lead of the study, said. “Whilst further study is needed into the shared mechanisms between the conditions, there is evidence high cholesterol can transfer into the central nervous system, resulting in abnormal cholesterol metabolism in the brain. There is also evidence suggesting abnormal blood lipids may be caused or made worse by gut bacteria (H.pylori), all of which support the potential roles of abnormal lipids in AD and gut disorders. For example, elevated cholesterol in the brain has been linked to brain degeneration and subsequent cognitive impairment.” The research also supports the theory that some cholesterol-lowering drugs, such as statins might be beneficial in treating both AD and gut disorders. More research is needed. A New Approach to Treating Cystic Fibrosis Researchers at Cold Spring Harbor Laboratory discovered how antisense oligonucleotides (ASOs) could create a protein missing in cystic fibrosis (CF) patients. ASOs are molecules that can be leveraged to control cellular protein levels. CF is caused by any one of hundreds of mutations in the gene that encodes for a protein called CFTR. The research group found a new way to use ASOs to make more of a functional, although not perfect, version of CFTR. The imperfect CFTR protein is caused by a gene mutation, which results in cells receiving the wrong instructions for making the CFTR protein. The mistaken instructions are eliminated, and the protein isn’t made. But what the research did was trick the cells into using the imperfect instructions and making the slightly abnormal CFTR protein. In CF, they found that an imperfect CFTR protein is better than none. This approach improved lung cell function. A Better Understanding of How Melanoma Spreads in the Brain Investigators with Columbia University Irving Medical Center completed what is believed to be one of the most comprehensive studies of the cells inside melanoma brain metastases. It’s not well understood why melanoma, a kind of skin cancer, spreads to the brain and generally has lower response rates to many treatments. The researchers invented new techniques for analyzing single-cell genetics of frozen brain samples, which allowed them to analyze tissue from patients who had not been treated. They analyzed the genes expressed in more than 100,000 individual cells. They found that melanoma brain metastases are more chromosomally unstable than melanoma metastases in other body parts. This, in turn, triggers signaling pathways that increase the likelihood of metastases and the ability of the cancer cells to suppress the immune system. They believe these newfound pathways could be potential targets for new therapies. How Belly Fat Increases Risk of Metabolic Disease Researchers with King’s College London studied data from TwinsUK to learn more about how belly fat increases the risk of metabolic disease. They leveraged samples from 538 participants that combined genetic, gene function, diet, and health data. Their particular focus was epigenetic markers. These are like molecular switches that turn genes on or off based on different environmental factors. One was a gene where the identified epigenetic changes were known to be a potential mechanism where diet affects belly fat accumulation. Others were epigenetic markers that have effects on metabolic health. They were able to develop an epigenetic predictor of insulin resistance associated with their findings of elevated belly fat. After controlling for BMI, the SAT methylome showed a distinct epigenetic signature linked with visceral fat. Booster Shots Help Battle Omicron The Omicron subvariants of COVID-19 are particularly adept at evading immunity caused by previous infection and vaccines. However, a new study out of the University of Washington School of Medicine/UW Medicine evaluated a panel of vaccines available in the U.S. and globally and found that booster shots offset some of these variants’ immune evasion tactics. The research supported earlier evidence that a third vaccine dose expands existing memory B cells specific to the viral spike protein as well as stimulating new memory B cells. This causes the production of antibodies with enhanced potency against the Omicron subvariants. Their research also showed that the Omicron BA.5, which along with BA.4, is now the dominant strain globally, has an ability to bind with its host ACE2 receptor that is six times stronger than the ancestral SARS-CoV-2 (Wuhan) strain. However, they’re all slower at the next step, fusing with the membrane on the host cell. They evaluated vaccines produced by Moderna, Pfizer-BioNTech, Novavax, Janssen (J&J), AstraZeneca, Sinopharm and Sputnik V. The authors wrote, “The marked improvement in plasma neutralizing activity for subjects that received a booster dose over those that did not highlights the importance of vaccine boosters for eliciting potent neutralizing antibody responses against Omicron sublineages.”