Macrophage LRRK2 hyperactivity impairs autophagy and induces Paneth cell dysfunction.

polymorphisms (G2019S/N2081D) that increase susceptibility to Parkinson's disease and Crohn's disease (CD) lead to LRRK2 kinase hyperactivity and suppress autophagy. This connection suggests that LRRK2 kinase inhibition, a therapeutic strategy being explored for Parkinson's disease, may also benefit patients with CD. Paneth cell homeostasis is tightly regulated by autophagy, and their dysfunction is a precursor to gut inflammation in CD.

Influence of Early Life Factors, including breast milk Composition, on the Microbiome of Infants Born to Mothers with and without Inflammatory Bowel Disease.

Background And Aims: Herein we analysed the influence of early life factors, including breast milk composition, on the development of the intestinal microbiota of infants born to mothers with and without IBD.

Methods: The MECONIUM [Exploring MEChanisms Of disease traNsmission In Utero through the Microbiome] study is a prospective cohort study consisting of pregnant women with or without IBD and their infants. Longitudinal stool samples were collected from babies and analysed using 16s rRNA sequencing and faecal calprotectin.

Long-Term Outcomes of the Excluded Rectum in Crohn's Disease: A Multicenter International Study.

Background: Many patients with Crohn's disease (CD) require fecal diversion. To understand the long-term outcomes, we performed a multicenter review of the experience with retained excluded rectums.

Methods: We reviewed the medical records of all CD patients between 1990 and 2014 who had undergone diversionary surgery with retention of the excluded rectum for at least 6 months and who had at least 2 years of postoperative follow-up.

Breastfeeding Is Associated with Lower Likelihood of Helicobacter Pylori Colonization in Babies, Based on a Prospective USA Maternal-Infant Cohort.

Background: Mother-to-child transmission of Helicobacter pylori (H. pylori) is the primary source of intrafamilial spread in early childhood in regions of high H. pylori prevalence.

Chronic Exposure to Palmitic Acid Down-Regulates AKT in Beta-Cells through Activation of mTOR.

High circulating lipids occurring in obese individuals and insulin-resistant patients are considered a contributing factor to type 2 diabetes. Exposure to high lipid concentration is proposed to both protect and damage beta-cells under different circumstances. Here, by feeding mice a high-fat diet (HFD) for 2 weeks to up to 14 months, the study showed that HFD initially causes the beta-cells to expand in population, whereas long-term exposure to HFD is associated with failure of beta-cells and the inability of animals to respond to glucose challenge.

Transformation of SOX9 cells by Pten deletion synergizes with steatotic liver injury to drive development of hepatocellular and cholangiocarcinoma.

SOX9 (Sex-determining region Y Box 9) is a well-characterized transcription factor that is a marker for progenitor cells in various tissues. In the liver, cells delineated by SOX9 are responsible for regenerating liver parenchyma when cell proliferation is impaired following chronic injury. However, whether these SOX9 cells play a role in liver carcinogenesis has not been fully understood, although high SOX9 expression has been linked to poor survival outcome in liver cancer patients.

Longitudinal Changes in Fecal Calprotectin Levels Among Pregnant Women With and Without Inflammatory Bowel Disease and Their Babies.

Background & Aims: The effect of pregnancy on inflammatory bowel disease (IBD) remains poorly understood. We aimed to monitor intestinal inflammation using fecal calprotectin (FC) in pregnant women and their babies during early life.

Methods: Pregnant women with or without IBD and their infants were prospectively enrolled.

A dietary intervention to improve the microbiome composition of pregnant women with Crohn's disease and their offspring: The MELODY (Modulating Early Life Microbiome through Dietary Intervention in Pregnancy) trial design.

Crohn's disease (CD), a type of inflammatory bowel disease (IBD), is a chronic condition of the gastrointestinal tract that is caused by the loss of mucosal tolerance towards the commensal bacteria resulting in inflammatory responses. It has long been postulated that the gut microbiota, a complex and dynamic population of microorganisms, plays a key role in the pathogenesis of IBD. Maternal diagnosis of IBD has been identified as the greatest risk factor for IBD in offspring increasing the odds of developing the disease >4.

AKT1 Regulates Endoplasmic Reticulum Stress and Mediates the Adaptive Response of Pancreatic β Cells.

Isoforms of protein kinase B (also known as AKT) play important roles in mediating insulin and growth factor signals. Previous studies have suggested that the AKT2 isoform is critical for insulin-regulated glucose metabolism, while the role of the AKT1 isoform remains less clear. This study focuses on the effects of AKT1 on the adaptive response of pancreatic β cells.