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Washington, D.C., So far, microbiome research is a lot like the fable of the blind men and the elephant. How much can you learn about an elephant by only looking at its tail? Researchers have studied what's most readily available — feces collected from toilets — but missed the microbial masterminds upstream of the small intestine. Until recently.
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Some scientists liken the microbiome to another human organ; the microbiome is the collective name for the tens of trillions of interconnected microorganisms that live in and on our bodies. They act as miniature sentinels that protect our surfaces from invading pathogens. In the upper intestine, different microbial populations help with digestion, metabolism, and even immunity.
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I am a gastroenterologist who has spent the past 20 years studying the role of the microbiome in health and disease. Advances in technology are enabling scientists to study the small intestinal microbiome, potentially improving our understanding and treating many diseases.
Big changes come from small things
Certain members of the small intestinal microbiota are associated with obesity and overweight, while others are associated with a healthy metabolic state. Indeed, the microbes in the small intestine aid digestion by converting certain simple carbohydrates into molecular building blocks for a healthy gut and body.
Although small intestinal metabolites are similar in function to those in the colon, they are quite different from the fiber-derived metabolites of the large intestinal microbiota. Some small intestinal metabolites help regulate the upper intestinal production of GIP, a sister molecule to the lower intestinal hormone GLP-1, which constitutes the weight loss and type 2 diabetes drugs Wegovy and Ozempic. Along with another lower intestinal hormone called PYY, these three are important in orchestrating the body's response to food by regulating appetite and blood sugar levels.
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Monjaro has an incrementally more potent combination of GIP and GLP-1 compared to Wegovy and Ozempic. Full replacement of these hormones is naturally stimulated by the breakdown of their products from the microbiota in both the large and small intestine.
Research has linked disruptions to the small intestinal microbiome to a range of intestinal disorders, including irritable bowel syndrome, small intestinal bacterial overgrowth, Crohn's disease and celiac disease.
These diseases are thought to arise in part from disruptions in how the microbiome breaks down food. For example, celiac disease is associated with a reduced ability of the small intestinal microbiome to digest gluten. IBS and SIBO are associated with the reverse – the ability of the small intestinal microbiome to over-ferment fiber and sugars.
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Foods high in FODM (fermentable short chain carbohydrates), such as wheat, garlic, onions, legumes, and certain processed foods, have been found to contribute to symptoms in people with SIBO and IBS. Dairy products, high in lactose, are a high FODM food group that are linked to lactose intolerance and are associated with an overactive small intestinal microbiota.
Diseases associated with the small intestinal microbiota are not just metabolic or gut-related: the intestinal lining houses a virtual embassy of immune cells that are constantly vigilantly monitoring the motley flow of microbial and nutritional antigens passing through the intestine.
Faults in the security system that isolates waste from the rest of the body, and in the process that suppresses the immune response, are suspected to be behind a range of autoimmune diseases in which the body becomes confused about who is friend and who is foe.
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Research has shown that inflammatory changes in the small intestinal microbiome are associated with extraintestinal manifestations of type 1 diabetes, in which circulating immune cells attack insulin-producing cells in the pancreas, and celiac disease, in which immune cells can trigger destructive processes in the eyes, skin, and joints of the body.
Until very recently, research into the small intestine has progressed slowly, relying on upper endoscopies, in which a sedated patient is given a tube the size of a pinkie, equipped with a tiny camera on the end, inserted through the mouth into the first part of the small intestine.
One of the few alternatives to endoscopy involves studying patients who have had intestinal surgery that involves cutting a hole in the abdominal wall, leaving a direct access to the small intestine.
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Newly developed techniques are helping scientists obtain samples from the deepest parts of the gut, without the need for sedation or special anatomical conditions. These techniques include camera capsules tethered to strings the size of angel hair, and other more streamlined devices that create a minimally invasive, direct-access line into the small intestine. Researchers have also developed capsules with sample compartments that open when a certain acidity level is reached in the body.
These new sampling techniques allow unprecedented access to the upper intestine, paving the way for new insights and treatments. In a real-world rendition of the childhood favorite, “Magic School Bus Inside the Body,” researchers can now navigate the gut just like Ms. Frizzle and her classmates, shedding light on the microbial secrets that lie hidden within our gut.
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Therapies based on our nascent understanding of the gut microbiome include approaches ranging from probiotics to fecal transplants, prebiotics to fermented foods.
However, new therapies for gut health are still in their infancy. Studying the small intestine may provide insights to improve the development of treatments. Promising future possibilities include pairing small intestinal bacteria with their preferred prebiotics, or personalized combinations of low-FODM prebiotics designed to avoid small intestinal fermentation.
Combining food and microbiome therapy is likely a harbinger of what is to come in the rapidly developing field of microbiome medicine. Research into the small intestine, not just the distal intestine, may be the most pioneering upstream start to microbiome medicine. RUP
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News / Science / Feces is a great target for microbiome research, but a look into the small intestine reveals new ways to improve gut health
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