nature: unprecedented look at the human small intestine reveals secrets of absorbing nutrients and avoiding infection
2024-09-03
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the small intestine is an important organ for absorbing nutrients in the human body. its average length can reach 6 meters. millions of villus-like protrusions are formed on the inner wall, which greatly increases the surface area of this section of the digestive tract.each intestinal villus is only 0.5 to 1.5 mm long, but from the crypts at the root close to the inner wall to the protruding villus tip, both gene expression and metabolic function are very different.in a paper recently published in the journal nature, scientists from the weizmann institute of science in israel constructed a comprehensive spatial expression map that clearly showsspatial heterogeneity of small intestinal villi in adults。professor shalev itzkovitz, the corresponding author of the study, had previously analyzed the small intestine of mice in detail and found that cells with different relative positions on the villi of the small intestine perform different functions.analyzing the human gut is much more difficult, primarily because samples are difficult to obtain.。in this study, scientists worked with surgeons to obtain human intestinal tissue removed during surgery. the patients who provided the samples underwent a whipple procedure for diseases such as pancreatic cancer. in addition to the diseased head of the pancreas, the first part of the small intestine, the duodenum, also needed to be removed. the researchers were able to analyze this section of healthy intestinal tissue.using spatial transcriptomics, spatial proteomics, and single-molecule fluorescence in situ hybridization techniques, the authors reconstructed a comprehensive spatial expression map of the duodenum and analyzed the gene expression characteristics of cells in different regions at a resolution of 50 microns.▲fluorescence imaging of human small intestine tissue samples, with different proteins labeled in different colors(image source: reference [1])according to this map, the researchersa puzzle about fat absorption in the small intestineprovides an answer. scientists have long discovered that fat in food is not absorbed into the blood quickly, sometimes with a delay of up to two days. this study found that the small intestinal epithelial cells have an "assembly line" when absorbing lipids. when they are located at the root of the villi, they are responsible for assembling lipid droplets. these cells then gradually migrate along the villi until they reach the tip, where they synthesize chylomicrons and transport cholesterol from food from the epithelial cells through the lymphatic vessels into the blood circulation.similarly, these migratory epithelial cells also take up iron at the roots and release it into the blood when they reach the tips. in addition, many enzymes required for digestion of nutrients such as amino acids, peptides, and sugars are mostly absorbed or produced at the tips of the villi, while cells that absorb vitamins and minerals are concentrated at the roots of the villi.▲the characteristic proteins expressed in different regions of the villi from the root to the tip(image source: reference [1])in addition to how the small intestine absorbs nutrients, the atlas also reveals characteristics of the small intestine's ability to resist infection. the researchers found that some cells at the tips of the villi secrete antimicrobial proteins that can either attack bacteria directly or send a distress signal to the immune system, therebyrecruitment of pro-inflammatory immune cells such as macrophages to the tip。while compiling this intestinal cell atlas, the researchers also unexpectedly discovered an anatomical structure that was different from what they had previously known. usually in anatomy textbooks, the villi of the small intestine of a healthy human body are described as straight finger-like protrusions, and only in the case of cancer will the villi have many branches. in this study, in order to record the spatial structure of the tissue in three dimensions without destroying the integrity of the tissue, the researchers used a new technical method and found thathuman small intestinal villi contain abundant serrated and branched villi, which are concentrated at the top of the circular folds., which helps to further increase the surface area of the small intestine and improve absorption.as the authors note in the paper abstract, "this study provides a detailed resource for understanding the biology of the adult small intestine. our atlas provides answers to basic questions and can be applied to clinical problems." professor shalev itzkovitz, the corresponding author of the study, said, "now that we have mapped the healthy small intestine, we can further understand the changes that the small intestine undergoes in disease, aging, taking certain medications or eating a specific diet."
