Authors: Rachel K Zwick, Petr Kasparek, Brisa Palikuqi...

A key aspect of nutrient absorption is the exquisite division of labour across the length of the small intestine, with individual nutrients taken up at different proximal:distal positions. For millennia, the small intestine was thought to comprise three segments with indefinite borders: the duodenum, jejunum and ileum. By examining the fine-scale longitudinal transcriptional patterns that span the mouse and human small intestine, we instead identified five domains of nutrient absorption that mount distinct responses to dietary changes, and three regional stem cell populations. Molecular domain identity can be detected with machine learning, which provides a systematic method to computationally identify intestinal domains in mice. We generated a predictive model of transcriptional control of domain identity and validated the roles of Ppar-δ and Cdx1 in patterning lipid metabolism-associated genes. These findings represent a foundational framework for the zonation of absorption across the mammalian small intestine.

Topics: Humans; Mice; Animals; Intestine, Small; Duodenum; Intestines; Jejunum; Ileum; Mammals

PubMed: 38321203
DOI: 10.1038/s41556-023-01337-z

Authors: Kristina Martinez-Guryn, Nathaniel Hubert, Katya Frazier...

The gut microbiota play important roles in lipid metabolism and absorption. However, the contribution of the small bowel microbiota of mammals to these diet-microbe interactions remains unclear. We determine that germ-free (GF) mice are resistant to diet-induced obesity and malabsorb fat with specifically impaired lipid digestion and absorption within the small intestine. Small bowel microbes are essential for host adaptation to dietary lipid changes by regulating gut epithelial processes involved in their digestion and absorption. In addition, GF mice conventionalized with high-fat diet-induced jejunal microbiota exhibit increased lipid absorption even when fed a low-fat diet. Conditioned media from specific bacterial strains directly upregulate lipid absorption genes in murine proximal small intestinal epithelial organoids. These findings indicate that proximal gut microbiota play key roles in host adaptability to dietary lipid variations through mechanisms involving both the digestive and absorptive phases and that these functions may contribute to conditions of over- and undernutrition.

Topics: Animals; Diet; Gastrointestinal Microbiome; Intestine, Small; Lipid Metabolism; Mice

PubMed: 29649441
DOI: 10.1016/j.chom.2018.03.011

Review

Authors: Giuseppe Losurdo, Fulvio Salvatore D'Abramo, Giuseppe Indellicati...

Small intestinal bacterial overgrowth (SIBO) is a condition hallmarked by an increase in the concentration of colonic-type bacteria in the small bowel. Watery diarrhea, bloating, abdominal pain and distension are the most common clinical manifestations. Additionally, malnutrition and vitamin (B12, D, A, and E) as well as minerals (iron and calcium) deficiency may be present. SIBO may mask or worsen the history of some diseases (celiac disease, irritable bowel disease), may be more common in some extra-intestinal disorders (scleroderma, obesity), or could even represent a pathogenetic link with some diseases, in which a perturbation of intestinal microbiota may be involved. On these bases, we performed a review to explore the multiple links between SIBO and digestive and extra-intestinal diseases.

Topics: Animals; Blind Loop Syndrome; Disease; Humans; Intestine, Small

PubMed: 32429454
DOI: 10.3390/ijms21103531

Authors: Seungil Kim, Yun-Chan Shin, Tae-Young Kim...

Mucin-degrading bacteria are densely populated in the intestinal epithelium; however, their interaction with intestinal stem cells (ISCs) and their progeny have not been elucidated. To determine whether mucin-degrading bacteria play a role in gut homeostasis, mice were treated with , a specialized species that degrades mucin. Administration of for 4 weeks accelerated the proliferation of Lgr5 ISCs and promoted the differentiation of Paneth cells and goblet cells in the small intestine (SI). We found similar effects of in the colon. The levels of acetic and propionic acids were higher in the cecal contents of -treated mice than in PBS-treated mice. SI organoids treated with cecal contents obtained from -treated mice were larger and could be diminished by treatment with G protein-coupled receptor (Gpr) 41/43 antagonists. Pre-treatment of mice with reduced gut damage caused by radiation and methotrexate. Further, a novel isotype of the strain was isolated from heathy human feces that showed enhanced function in intestinal epithelial regeneration. These findings suggest that mucin-degrading bacteria (e.g., ) may play a crucial role in promoting ISC-mediated epithelial development and contribute to intestinal homeostasis maintenance.

Topics: Akkermansia; Animals; Cell Differentiation; Cell Proliferation; Epithelial Cells; Fatty Acids, Volatile; Feces; Female; Gastrointestinal Microbiome; Homeostasis; Humans; Intestinal Mucosa; Intestine, Small; Methotrexate; Mice; Mice, Inbred C57BL; Mucins; Stem Cells; Wnt Signaling Pathway

PubMed: 33678130
DOI: 10.1080/19490976.2021.1892441

Review

Authors: M Y Beg, L Bains, P Lal...

INTRODUCTION

Intertwining of bowel loops to form a knot is very rare cause of intestinal obstruction. Among intestinal knots, ileoileal knotting is the most rare, with only a handful of cases reported in literature. We present a rare case of ileoileal knotting and review of small bowel knots. The aim of this review was to summarise the existing evidence on small bowel knots and to postulate the possible mechanisms for knotting.

METHODS

A systematic search was conducted for literature published up to December 2019 using MEDLINE, PubMed and Google Scholar databases, together with the references of the full-text articles retrieved. Papers with case reports of small bowel knots were considered to be eligible for inclusion in the review.

FINDINGS

A total of 14 case reports were evaluated. There was no clear predilection for age or sex. Mostly cases were from Asia and Africa with no cases from the West. The presenting complaints were abdominal pain (93%), vomiting (64%), abdominal distention (57 %) and obstipation (43%). The bowel was gangrenous in 78% of cases. All underwent exploration, with the majority requiring resection and anastomosis of the involved segment.

CONCLUSION

Ileoileal knotting is a very rare cause of intestinal obstruction. Possible mechanisms include loaded bowel with longer mesentery, vigorous peristalsis, single bulky meal, pregnancy and intussusception. The condition is extremely difficult to diagnose preoperatively and it is usually diagnosed intraoperatively. The standard of treatment is resection of gangrenous part and anastomosis.

Topics: Abdominal Pain; Adult; Aged; Aged, 80 and over; Female; Gangrene; Humans; Infant; Intestinal Obstruction; Intestinal Volvulus; Intestine, Small; Intussusception; Male; Middle Aged; Vomiting; Young Adult

PubMed: 32538120
DOI: 10.1308/rcsann.2020.0122

Review

Authors: Hugh James Freeman

Spontaneous free perforation of the small intestine is uncommon, especially if there is no prior history of visceral trauma. However, free, even recurrent, perforation may complicate a defined and established clinical disorder, such as Crohn's disease. In addition, free perforation may be the initial clinical presentation of an occult intestinal disorder, such as a lymphoma complicating celiac disease, causing diffuse peritonitis and an acute abdomen. Initial diagnosis of the precise cause may be difficult, but now has been aided by computerized tomographic imaging. The site of perforation may be helpful in defining a cause (e.g., ileal perforation in Crohn's disease, jejunal perforation in celiac disease, complicated by lymphoma or collagenous sprue). Urgent surgical intervention, however, is usually required for precise diagnosis and treatment. During evaluation, an expanding list of other possible causes should be considered, even after surgery, as subsequent management may be affected. Free perforation may not only complicate an established intestinal disorder, but also a new acute process (e.g., caused by different infectious agents) or a longstanding and unrecognized disorder (e.g., congenital, metabolic and vascular causes). Moreover, new endoscopic therapeutic and medical therapies, including use of emerging novel biological agents, have been complicated by intestinal perforation. Recent studies also support the hypothesis that perforation of the small intestine may be genetically-based with different mutations causing altered connective tissue structure, synthesis and repair.

Topics: Adult; Humans; Intestinal Perforation; Intestine, Small; Predictive Value of Tests; Prognosis; Recurrence; Risk Factors; Rupture, Spontaneous

PubMed: 25110427
DOI: 10.3748/wjg.v20.i29.9990

Authors: Steven Timmermans, Charlotte Wallaeys, Natalia Garcia-Gonzalez...

The small intestinal crypts harbor secretory Paneth cells (PCs) which express bactericidal peptides that are crucial for maintaining intestinal homeostasis. Considering the diverse environmental conditions throughout the course of the small intestine, multiple subtypes of PCs are expected to exist. We applied single-cell RNA-sequencing of PCs combined with deep bulk RNA-sequencing on PC populations of different small intestinal locations and discovered several expression-based PC clusters. Some of these are discrete and resemble tuft cell-like PCs, goblet cell (GC)-like PCs, PCs expressing stem cell markers, and atypical PCs. Other clusters are less discrete but appear to be derived from different locations along the intestinal tract and have environment-dictated functions such as food digestion and antimicrobial peptide production. A comprehensive spatial analysis using Resolve Bioscience was conducted, leading to the identification of different PC's transcriptomic identities along the different compartments of the intestine, but not between PCs in the crypts themselves.

Topics: Paneth Cells; Animals; Intestine, Small; Mice; Mice, Inbred C57BL; Transcriptome; Single-Cell Analysis

PubMed: 39273007
DOI: 10.3390/cells13171435

Review

Authors: Shiloh R Lueschow, Steven J McElroy

Paneth cells were first described in the late 19th century by Gustav Schwalbe and Josef Paneth as columnar epithelial cells possessing prominent eosinophilic granules in their cytoplasm. Decades later there is continued interest in Paneth cells as they play an integral role in maintaining intestinal homeostasis and modulating the physiology of the small intestine and its associated microbial flora. Paneth cells are highly specialized secretory epithelial cells located in the small intestinal crypts of Lieberkühn. The dense granules produced by Paneth cells contain an abundance of antimicrobial peptides and immunomodulating proteins that function to regulate the composition of the intestinal flora. This in turn plays a significant role in secondary regulation of the host microvasculature, the normal injury and repair mechanisms of the intestinal epithelial layer, and the levels of intestinal inflammation. These critical functions may have even more importance in the immature intestine of premature infants. While Paneth cells begin to develop in the middle of human gestation, they do not become immune competent or reach their adult density until closer to term gestation. This leaves preterm infants deficient in normal Paneth cell biology during the greatest window of susceptibility to develop intestinal pathology such as necrotizing enterocolitis (NEC). As 10% of infants worldwide are currently born prematurely, there is a significant population of infants contending with an inadequate cohort of Paneth cells. Infants who have developed NEC have decreased Paneth cell numbers compared to age-matched controls, and ablation of murine Paneth cells results in a NEC-like phenotype suggesting again that Paneth cell function is critical to homeostasis to the immature intestine. This review will provide an up to date and comprehensive look at Paneth cell ontogeny, the impact Paneth cells have on the host-microbial axis in the immature intestine, and the repercussions of Paneth cell dysfunction or loss on injury and repair mechanisms in the immature gut.

Topics: Animals; Enterocolitis, Necrotizing; Humans; Infant, Newborn; Infant, Premature; Intestine, Small; Paneth Cells

PubMed: 32308658
DOI: 10.3389/fimmu.2020.00587

Review

Authors: Asadullah Madni, Sadia Rehman, Humaira Sultan...

Targeting the small intestine employing nanotechnology has proved to be a more effective way for site-specific drug delivery. The drug targeting to the small intestine can be achieved via nanoparticles for its optimum bioavailability within the systemic circulation. The small intestine is a remarkable candidate for localized drug delivery. The intestine has its unique properties. It has a less harsh environment than the stomach, provides comparatively more retention time, and possesses a greater surface area than other parts of the gastrointestinal tract. This review focuses on elaborating the intestinal barriers and approaches to overcome these barriers for internalizing nanoparticles and adopting different cellular trafficking pathways. We have discussed various factors that contribute to nanocarriers' cellular uptake, including their surface chemistry, surface morphology, and functionalization of nanoparticles. Furthermore, the fate of nanoparticles after their uptake at cellular and subcellular levels is also briefly explained. Finally, we have delineated the strategies that are adopted to determine the cytotoxicity of nanoparticles.

Topics: Animals; Biological Availability; Biological Transport; Drug Carriers; Drug Delivery Systems; Humans; Intestine, Small; Nanoparticles; Subcellular Fractions

PubMed: 33221968
DOI: 10.1208/s12249-020-01873-z

Review

Authors: Yogi A Patel, Pankaj J Pasricha

The small intestine is the longest organ in the human body, spanning a length of ∼5 m and compartmentalized into three distinct regions with specific roles in maintenance of comprehensive homeostasis. Along its length exists as a unique and independent system-called the enteric nervous system (ENS)-which coordinates the multitude of functions continuously around the clock. Yet, with so many vital roles played, the functions, relationships, and roles of the small intestine and ENS remain largely elusive. This fundamental hole in the physiology of the small intestine and ENS introduces a substantial number of challenges when attempting to create bioelectronic approaches for treatment of various disorders originating in the small intestine. Here, we review existing therapeutic options for modulating the small intestine, discuss fundamental gaps that must be addressed, and highlight novel methods and approaches to consider for development of bioelectronic approaches aiming to modulate the small intestine.

Topics: Animals; Enteric Nervous System; Gastrointestinal Microbiome; Homeostasis; Humans; Intestine, Small

PubMed: 30858329
DOI: 10.1101/cshperspect.a034355