Role of Vitamin K in Intestinal Health

Intestinal diseases, such as inflammatory bowel diseases (IBDs) and colorectal cancer (CRC) generally characterized by clinical symptoms, including malabsorption, intestinal dysfunction, injury, and microbiome imbalance, as well as certain secondary intestinal disease complications, continue to be serious public health problems worldwide. The role of vitamin K (VK) on intestinal health has drawn growing interest in recent years. In addition to its role in blood coagulation and bone health, several investigations continue to explore the role of VK as an emerging novel biological compound with the potential function of improving intestinal health. This study aims to present a thorough review on the bacterial sources, intestinal absorption, uptake of VK, and VK deficiency in patients with intestinal diseases, with emphasis on the effect of VK supplementation on immunity, anti-inflammation, intestinal microbes and its metabolites, antioxidation, and coagulation, and promoting epithelial development. Besides, VK-dependent proteins (VKDPs) are another crucial mechanism for VK to exert a gastroprotection role for their functions of anti-inflammation, immunomodulation, and anti-tumorigenesis. In summary, published studies preliminarily show that VK presents a beneficial effect on intestinal health and may be used as a therapeutic drug to prevent/treat intestinal diseases, but the specific mechanism of VK in intestinal health has yet to be elucidated.

TALPID3/KIAA0586 Regulates Multiple Aspects of Neuromuscular Patterning During Gastrointestinal Development in Animal Models and Human

TALPID3/KIAA0586 is an evolutionary conserved protein, which plays an essential role in protein trafficking. Its role during gastrointestinal (GI) and enteric nervous system (ENS) development has not been studied previously. Here, we analyzed chicken, mouse and human embryonic GI tissues with TALPID3 mutations. The GI tract of TALPID3 chicken embryos was shortened and malformed. Histologically, the gut smooth muscle was mispatterned and enteric neural crest cells were scattered throughout the gut wall. Analysis of the Hedgehog pathway and gut extracellular matrix provided causative reasons for these defects. Interestingly, chicken intra-species grafting experiments and a conditional knockout mouse model showed that ENS formation did not require TALPID3, but was dependent on correct environmental cues. Surprisingly, the lack of TALPID3 in enteric neural crest cells (ENCC) affected smooth muscle and epithelial development in a non-cell-autonomous manner. Analysis of human gut fetal tissues with a KIAA0586 mutation showed strikingly similar findings compared to the animal models demonstrating conservation of TALPID3 and its necessary role in human GI tract development and patterning.

A deep learning framework for quantitative analysis of actin microridges

Microridges are evolutionarily conserved actin-rich protrusions present on the apical surface of the squamous epithelial cells. In zebrafish epidermal cells, microridges form self-evolving patterns due to the underlying actomyosin network dynamics. However, their morphological and dynamic characteristics have remained poorly understood owing to lack of automated segmentation methods. We achieved ~97% pixel-level accuracy with the deep learning microridge segmentation strategy enabling quantitative insights into their bio-physical-mechanical characteristics. From the segmented images, we estimated an effective microridge persistence length as ~0.61μm. We discovered the presence of mechanical fluctuations and found relatively greater stresses stored within patterns of yolk than flank, indicating distinct regulation of their actomyosin networks. Furthermore, spontaneous formations and positional fluctuations of actin clusters within microridge influenced pattern rearrangements over short length/time-scales. Our framework allows large-scale spatiotemporal analysis of microridges during epithelial development and probing of their responses to chemical and genetic perturbations to unravel the underlying patterning mechanisms.

Oregano Essential Oils Promote Rumen Digestive Ability by Modulating Epithelial Development and Microbiota Composition in Beef Cattle

This study aimed to explore the effects of oregano essential oils (OEO) on the rumen digestive ability using multi-omics sequencing techniques. Twenty-seven castrated Pingliang red cattle were randomly separated into three groups (3 cattle/pen; n = 9) and fed on a daily basal diet supplemented with 0 (Con group), 130 mg (L group), and 260 mg (H group) OEO. The finishing trial lasted for 390 days, and all cattle were slaughtered to collect rumen tissue and content samples. We found that the rumen papillae length in the H group was higher than in the Con group. Amylase concentrations were decreased in the H group than the Con group, whereas the β-glucosidase and cellulase concentrations increased. Compared to the Con group, the relative abundance of propionate and butyrate in the H group was significantly higher. Higher relative abundance of Parabacteroides distasonis and Bacteroides thetaiotaomicron were observed with increasing OEO concentration. The function of rumen microbiota was enriched in the GH43_17 family, mainly encoding xylanase. Besides, metabolites, including heparin, pantetheine, sorbic acid, aspirin, and farnesene concentrations increased with increasing OEO dose. A positive correlation was observed between Parabacteroides distasonis, Bacteroides thetaiotaomicron, and β-glucosidase, cellulase and propionate. The abundance of Parabacteroides distasonis and Parabacteroides_sp._CAG:409 were positively correlated with sorbic acid and farnesene. In summary, OEO supplementation increased the rumen digestive ability by modulating epithelial development and microbiota composition in beef cattle. This study provides a comprehensive insight into the OEO application as an alternative strategy to improve ruminant health production.

Growth performances, gastrointestinal epithelium and bacteria responses of Yellow-feathered chickens to kudzu-leaf flavonoids supplement

The objective of this study was to investigate the effects of replacing antibiotics with Kudzu-leaf flavonoids (KLF) on the growth performances, gut epithelial development, and gastrointestinal bacteria diversities of Yellow-feathered broilers. For this purpose, total of 216 1-day-old male Yellow-feathered chickens with the similar birth weight (31.0 ± 1.0 g) were randomly divided into 3 treatments: the control treatment (CON), the kudzu-leaf flavonoids supplement treatment (KLF), and the antibiotics supplement treatment (AGP). All birds were provided with a 56 d-feeding procedure, followed by the measurement of production performances, immune organs, blood anti-oxidant parameters, intestine epithelium development, and cecal microbiota. Results showed the feed conversion ratio significantly decreased after KLF supplement compared with CON (P < 0.05). KLF supplement partly promoted the anti-oxidant capacity on account of the increased activity of Superoxide dismutase (SOD) and the decrease content of malondialdehyde (MDA). Further, as referred to the gastrointestinal development and bacteria, ratio of villus/crypt significantly increased of ileum in KLF treatment (P < 0.05) while a significant promition of bacterial diversity and partial representative probiotic bacteria (P < 0.05) after KLF supplementation. Moreover, correlation analysis indicated that probitics including Bifidobacterium, Butyricimonas, Lactobacillus and Streptococcus positively correlated with production performances. In conclusion, KLF supplement may promote feed efficiency and benefit the gastrointestinal health through improving gut bacterial diversity and probiotic bacteria. The KLF might be applied as a proper antibiotic alternative.

The Mechanism of Secretion and Metabolism of Gut-Derived 5-Hydroxytryptamine

Serotonin, also known as 5-hydroxytryptamine (5-HT), is a metabolite of tryptophan and is reported to modulate the development and neurogenesis of the enteric nervous system, gut motility, secretion, inflammation, sensation, and epithelial development. Approximately 95% of 5-HT in the body is synthesized and secreted by enterochromaffin (EC) cells, the most common type of neuroendocrine cells in the gastrointestinal (GI) tract, through sensing signals from the intestinal lumen and the circulatory system. Gut microbiota, nutrients, and hormones are the main factors that play a vital role in regulating 5-HT secretion by EC cells. Apart from being an important neurotransmitter and a paracrine signaling molecule in the gut, gut-derived 5-HT was also shown to exert other biological functions (in autism and depression) far beyond the gut. Moreover, studies conducted on the regulation of 5-HT in the immune system demonstrated that 5-HT exerts anti-inflammatory and proinflammatory effects on the gut by binding to different receptors under intestinal inflammatory conditions. Understanding the regulatory mechanisms through which 5-HT participates in cell metabolism and physiology can provide potential therapeutic strategies for treating intestinal diseases. Herein, we review recent evidence to recapitulate the mechanisms of synthesis, secretion, regulation, and biofunction of 5-HT to improve the nutrition and health of humans.

Source and Impact of the EGF Family of Ligands on Intestinal Stem Cells

Epidermal Growth Factor (EGF) has long been known for its role in promoting proliferation of intestinal epithelial cells. EGF is produced by epithelial niche cells at the base of crypts in vivo and is routinely added to the culture medium to support the growth of intestinal organoids ex vivo. The recent identification of diverse stromal cell populations that reside underneath intestinal crypts has enabled the characterization of key growth factor cues supplied by these cells. The nature of these signals and how they are delivered to drive intestinal epithelial development, daily homeostasis and tissue regeneration following injury are being investigated. It is clear that aside from EGF, other ligands of the family, including Neuregulin 1 (NRG1), have distinct roles in supporting the function of intestinal stem cells through the ErbB pathway.