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Cell Aug 2023The gastrointestinal tract is in a state of constant motion. These movements are tightly regulated by the presence of food and help digestion by mechanically breaking...
The gastrointestinal tract is in a state of constant motion. These movements are tightly regulated by the presence of food and help digestion by mechanically breaking down and propelling gut content. Mechanical sensing in the gut is thought to be essential for regulating motility; however, the identity of the neuronal populations, the molecules involved, and the functional consequences of this sensation are unknown. Here, we show that humans lacking PIEZO2 exhibit impaired bowel sensation and motility. Piezo2 in mouse dorsal root, but not nodose ganglia is required to sense gut content, and this activity slows down food transit rates in the stomach, small intestine, and colon. Indeed, Piezo2 is directly required to detect colon distension in vivo. Our study unveils the mechanosensory mechanisms that regulate the transit of luminal contents throughout the gut, which is a critical process to ensure proper digestion, nutrient absorption, and waste removal.
Topics: Animals; Humans; Mice; Digestion; Gastrointestinal Transit; Ion Channels; Mechanotransduction, Cellular; Neurons
PubMed: 37541196
DOI: 10.1016/j.cell.2023.07.006 -
Nature Communications Jul 2023Mitochondria are the key organelles for sensing oxygen, which is consumed by oxidative phosphorylation to generate ATP. Lysosomes contain hydrolytic enzymes that degrade...
Mitochondria are the key organelles for sensing oxygen, which is consumed by oxidative phosphorylation to generate ATP. Lysosomes contain hydrolytic enzymes that degrade misfolded proteins and damaged organelles to maintain cellular homeostasis. Mitochondria physically and functionally interact with lysosomes to regulate cellular metabolism. However, the mode and biological functions of mitochondria-lysosome communication remain largely unknown. Here, we show that hypoxia remodels normal tubular mitochondria into megamitochondria by inducing broad inter-mitochondria contacts and subsequent fusion. Importantly, under hypoxia, mitochondria-lysosome contacts are promoted, and certain lysosomes are engulfed by megamitochondria, in a process we term megamitochondria engulfing lysosome (MMEL). Both megamitochondria and mature lysosomes are required for MMEL. Moreover, the STX17-SNAP29-VAMP7 complex contributes to mitochondria-lysosome contacts and MMEL under hypoxia. Intriguingly, MMEL mediates a mode of mitochondrial degradation, which we termed mitochondrial self-digestion (MSD). Moreover, MSD increases mitochondrial ROS production. Our results reveal a mode of crosstalk between mitochondria and lysosomes and uncover an additional pathway for mitochondrial degradation.
Topics: Humans; Lysosomes; Mitochondria; Hypoxia; Oxygen; Digestion
PubMed: 37433770
DOI: 10.1038/s41467-023-39811-9 -
Science (New York, N.Y.) Sep 2023Dietary fiber improves metabolic health, but host-encoded mechanisms for digesting fibrous polysaccharides are unclear. In this work, we describe a mammalian adaptation...
Dietary fiber improves metabolic health, but host-encoded mechanisms for digesting fibrous polysaccharides are unclear. In this work, we describe a mammalian adaptation to dietary chitin that is coordinated by gastric innate immune activation and acidic mammalian chitinase (AMCase). Chitin consumption causes gastric distension and cytokine production by stomach tuft cells and group 2 innate lymphoid cells (ILC2s) in mice, which drives the expansion of AMCase-expressing zymogenic chief cells that facilitate chitin digestion. Although chitin influences gut microbial composition, ILC2-mediated tissue adaptation and gastrointestinal responses are preserved in germ-free mice. In the absence of AMCase, sustained chitin intake leads to heightened basal type 2 immunity, reduced adiposity, and resistance to obesity. These data define an endogenous metabolic circuit that enables nutrient extraction from an insoluble dietary constituent by enhancing digestive function.
Topics: Animals; Mice; Chitin; Immunity, Innate; Lymphocytes; Obesity; Stomach; Adaptation, Physiological; Dietary Fiber; Chitinases; Digestion
PubMed: 37676935
DOI: 10.1126/science.add5649 -
Veterinary Medicine and Science Mar 2024Forages are widely used in horse diets. Different in vitro techniques are being tried to determine the fermentation levels of forages in the horse digestive tract.
BACKGROUND
Forages are widely used in horse diets. Different in vitro techniques are being tried to determine the fermentation levels of forages in the horse digestive tract.
OBJECTIVES
This study aimed to evaluate the digestion levels of four dry forages commonly used in horse nutrition: alfalfa herbage, meadow hay, wheat straw, and Italian ryegrass. In vitro total digestion (TDT), in vitro Sunvold-large intestine digestion (SDT) and in vitro Menke-large intestine digestion (MDT) techniques were compared.
METHODS
The study determined in vitro true dry matter digestion (T-DMD), in vitro true organic matter digestion (T-OMD) and in vitro true neutral detergent fibre digestion (T-NDFD). Additionally, concentrations of straight short-chain fatty acids (SCFAs; acetic acid - AA, propionic acid , butyric acid, and valeric acid ) and branched short-chain fatty acids (BSCFA) were assessed.
RESULTS
The highest in vitro T-DMD, T-OMD and T-NDFD values were determined by the in vitro TDT for the four forages (p < 0.05). In vitro T-DMD and T-OMD values of alfalfa herbage were higher than those of Italian ryegrass, meadow hay and wheat straw in the in vitro TDT (p < 0.001). In addition, in vitro T-DMD and T-OMD values of alfalfa herbage in the in vitro SDT were higher than those of meadow hay and wheat straw (p < 0.001). In the in vitro TDT, the molarity of AA, total SCFA and BSCFA in the digestion fluid of alfalfa herbage was higher than those of other forages (p < 0.05).
CONCLUSION
The in vitro total enzymatic + fermentative digestion technique for horse forages revealed higher values than the in vitro fermentative digestion techniques. In general, the higher the non-structural carbohydrate and crude protein contents in the forage, the higher the results of the in vitro TDT compared to the other techniques.
Topics: Animals; Horses; Animal Feed; Digestion; Diet; Triticum; Fatty Acids, Volatile; In Vitro Techniques
PubMed: 38369823
DOI: 10.1002/vms3.1373 -
BMC Immunology Oct 2023Digestive autoimmune conditions are a growing challenge to global health. Risk factors associated with autoimmune digestive diseases are complex, including genetic...
Digestive autoimmune conditions are a growing challenge to global health. Risk factors associated with autoimmune digestive diseases are complex, including genetic variation, immunological dysfunction, and various environmental factors. To improve our understanding of the mechanisms behind digestive autoimmune conditions, including factors causing gastrointestinal manifestations and pathogenesis, BMC Immunology has launched a new Collection "The digestive system and autoimmunity".
Topics: Humans; Autoimmunity; Autoimmune Diseases; Digestive System
PubMed: 37794375
DOI: 10.1186/s12865-023-00561-4 -
International Journal of Molecular... Aug 2023Piezo1, a non-selective cation channel directly activated by mechanical forces, is widely expressed in the digestive system and participates in biological functions... (Review)
Review
Piezo1, a non-selective cation channel directly activated by mechanical forces, is widely expressed in the digestive system and participates in biological functions physiologically and pathologically. In this review, we summarized the latest insights on Piezo1's cellular effect across the entire digestive system, and discussed the role of Piezo1 in various aspects including ingestion and digestion, material metabolism, enteric nervous system, intestinal barrier, and inflammatory response within digestive system. The goal of this comprehensive review is to provide a solid foundation for future research about Piezo1 in digestive system physiologically and pathologically.
Topics: Enteric Nervous System; Humans; Ion Channels; Digestive System; Mechanotransduction, Cellular; Animals
PubMed: 37629134
DOI: 10.3390/ijms241612953 -
Digestion 2024Functional endoscopy signifies a significant advancement in gastrointestinal examination, integrating motor function assessments alongside routine endoscopy findings.... (Review)
Review
BACKGROUND
Functional endoscopy signifies a significant advancement in gastrointestinal examination, integrating motor function assessments alongside routine endoscopy findings. Traditional gastrointestinal endoscopy primarily focuses on the detection of early-stage cancer by identifying morphological changes within the gastrointestinal tract. These alterations include modifications in lumen structure, color tone, and surface patterns, which can be diagnosed using endoscopic images that assess these morphological changes. In contrast, functional endoscopy aims to dynamically evaluate the peristaltic movements of the digestive tract and the presence or movement of reflux of digestive fluids during the endoscopic procedure. It also seeks to identify morphological changes such as hiatal hernias, as observed in conventional endoscopy. Consequently, relying solely on endoscopic images proves inadequate for diagnosis, necessitating continuous observation of these dynamic movements.
SUMMARY
The endoscopic pressure study integrated system (EPSIS) serves as an exemplar of functional endoscopy. It incorporates a stress test to assess the functionality of the lower esophageal sphincter (LES) through intragastric insufflation. A crucial element of EPSIS evaluation is the identification of the scope holding sign (SHS), which signifies LES contraction. EPSIS also encompasses the observation of esophageal peristaltic waves and the auditory detection of burping, providing a comprehensive diagnostic approach while observing the sphincter from a retroflex view on the stomach side. By integrating these dynamic findings, functional endoscopy offers an efficient method for diagnosing functional gastrointestinal diseases, such as gastroesophageal reflux disease (GERD).
KEY MESSAGES
Functional endoscopy combines motor function assessments with traditional endoscopy, enhancing the diagnostic capabilities of gastrointestinal examinations. Traditional endoscopy focuses on identifying morphological changes, while functional endoscopy evaluates dynamic movements, reflux, and sphincter functionality. EPSIS exemplifies functional endoscopy, featuring a stress test and the SHS for LES contraction assessment. EPSIS provides a comprehensive approach to diagnose GERD by integrating dynamic observations.
Topics: Humans; Gastroesophageal Reflux; Endoscopy, Gastrointestinal; Esophageal Sphincter, Lower; Hernia, Hiatal; Manometry
PubMed: 38008079
DOI: 10.1159/000534831