Genetic and observational associations of lung function with gastrointestinal tract diseases: pleiotropic and mendelian randomization analysis.

BACKGROUND: The two-way communications along the gut-lung axis influence the immune function in both gut and lung. However, the shared genetic characteristics of lung function with gastrointestinal tract (GIT) diseases remain to be investigated. METHODS: We first investigated the genetic correlations between three lung function traits and four GIT diseases. Second, we illustrated the genetic overlap by genome-wide pleiotropic analysis (PLACO) and further pinpointed the relevant tissue and cell types by partitioning heritability. Furthermore, we proposed pleiotropic genes as potential drug targets by drug database mining. Finally, we evaluated the causal relationships by epidemiologic observational study and Mendelian randomization (MR) analysis. RESULTS: We found lung function and GIT diseases were genetically correlated. We identified 258 pleiotropic loci, which were enriched in gut- and lung-specific regions marked by H3K4me1. Among these, 16 pleiotropic genes were targets of drugs, such as tofacitinib and baricitinib targeting TYK2 for the treatment of ulcer colitis and COVID-19, respectively. We identified a missense variant in TYK2, exhibiting a shared causal effect on FEV1/FVC and inflammatory bowel disease (rs12720356, PPLACO=1.38 × 10- 8). These findings suggested TYK2 as a promising drug target. Although the epidemiologic observational study suggested the protective role of lung function in the development of GIT diseases, no causalities were found by MR analysis. CONCLUSIONS: Our study suggested the shared genetic characteristics between lung function and GIT diseases. The pleiotropic variants could exert their effects by modulating gene expression marked by histone modifications. Finally, we highlighted the potential of pleiotropic analyses in drug repurposing.

Factors affecting gastrointestinal function recovery after cesarean section among Chinese mothers: A cross-sectional study.

This study was conducted to explore the influencing factors of gastrointestinal function recovery after cesarean section (CS), which could provide a reference for the enhanced recovery after surgery in obstetrics. This is a cross-sectional survey on Chinese mothers receiving CS. The participants's socio-demographic characteristics, perioperative diet, medical condition and gastrointestinal function after surgery were collected by a self-designed questionnaire. Binary logistic regression analysis was employed to explore the influencing factors of gastrointestinal function recovery after CS. A total of 1501 (94.76%) valid questionnaires were collected. The first borborygmus was 2.21 ± 0.63 hours, and the first anal exhaust was 35.73 ± 14.85 hours after the CS. The incidence of abdominal distension and intestinal obstruction were 15.1% and 0.7%, respectively. The parity, type of CS, 2-hours bleeding after surgery, time of first meal after surgery, whether taking peppermint water after surgery were the independent influencing factors for gastrointestinal function recovery after CS. We should pay more attention to the mothers with scarred uterus, manage the labor process strictly, and reduce 2-hours bleeding after surgery. The mothers with CS should also be encouraged to eat early and take peppermint water to promote intestinal peristalsis actively.

Microbiota intestinal y cólicos infantiles: ¿hay lugar para los prebióticos, probióticos y posbióticos? / Gut Microbiota and Infant Colic: is there a Place for Prebiotics, Probiotics, and Postbiotics?

El consumo de probióticos, prebióticos y posbióticos, o su combinación, puede contribuir a mantener una microbiota intestinal saludable ya que permite la regulación de su disbiosis en el caso de algunas enfermedades o trastornos, principalmente en los trastornos gastrointestinales funcionales (TGIF). El microbioma intestinal es protagonista esencial en la fisiopatología de los TGIF a través de sus funciones metabólicas y nutricionales, el mantenimiento de la integridad de la mucosa intestinal y la regulación de la respuesta inmunitaria. Las investigaciones realizadas hasta la fecha indican que los probióticos, prebióticos y posbióticos pueden tener efectos inmunomoduladores directos y clínicamente relevantes. Existen pruebas del uso de esta familia de bióticos en individuos sanos para mejorar la salud general y aliviar los síntomas en una serie de enfermedades como los cólicos infantiles. La colonización y establecimiento de la microbiota comienza en el momento del nacimiento; los primeros 2-3 años de vida son fundamentales para el desarrollo de una comunidad microbiana abundante y diversa. Diversos estudios científicos realizados mediante técnicas tradicionales dependientes de cultivo y más recientemente por técnicas moleculares han observado diferencias en las poblaciones bacterianas de bebés sanos y aquellos que sufren TGIF, estos últimos caracterizados por un aumento de especies patógenas y una menor población de bifidobacterias y lactobacilos, en comparación con los primeros. En tal contexto, se considera que la microbiota intestinal como protagonista en el desarrollo de esos trastornos, entre ellos los cólicos infantiles, a través de sus funciones metabólicas, nutricionales, de mantenimiento de la integridad de la mucosa intestinal y regulación de la respuesta inmunitaria. Esto ha abierto la puerta al estudio de la utilización de prebióticos, probióticos y posbióticos en el tratamiento y/o prevención de los TGIF infantiles. El parto vaginal y de término así como la lactancia son fundamentales en la constitución de una microbiota saludable. Como herramientas de apoyo, existen estudios de eficacia que sustentan la administración de esta familia de bióticos, principalmente en los casos en que la lactancia no sea posible o esté limitada. (AU)

The consumption of probiotics, prebiotics, and postbiotics, or a combination of them, can contribute to maintaining a healthy intestinal microbiota as it allows the regulation of its dysbiosis in the case of some diseases or disorders, mainly in functional gastrointestinal disorders (FGIDs). The gut microbiome is an essential player in the pathophysiology of FGIDs through its metabolic and nutritional functions, the maintenance of intestinal mucosal integrity, and the regulation of the immune response. Research results thus far indicate that probiotics, prebiotics, and postbiotics may have direct and clinically relevant immunomodulatory effects. There is evidence regarding the prescription of this family of biotics in healthy individuals to improve overall health and alleviate symptoms in many conditions like infantile colic. The colonization and microbiota establishment begins at birth; the first 2-3 years of life are critical for developing an abundant and diverse microbial community. Several scientific studies performed by traditional culture-dependent techniques and more recently by molecular techniques have observed differences in the bacterial populations of healthy infants and those suffering from FGIDs, the latter characterized by an increase in pathogenic species and a lower population of bifidobacteria and lactobacilli, compared to the former. In this context, the intestinal microbiota plays a leading role in the onset of these disorders, including infantile colic, through its metabolic and nutritional functions, maintenance of the integrity of the intestinal mucosa, and regulation of the immune response. That has opened the door to the study of prebiotics, probiotics, and postbiotics usage in the treatment and or prevention of infantile FGIDs. Vaginal and term delivery and breastfeeding are fundamental in the constitution of a healthy microbiota. As supportive tools, there are efficacy studies that support the administration of this family of biotics, mainly in cases where lactation is not possible or is limited.

Development of the digestive system in early infancy and nutritional management of digestive problems in breastfed and formula-fed infants.

Food digestion and absorption in infants are closely related to early growth and long-term health. Human milk and infant formula are the main food sources for 0-6 month-old infants. Due to the immature gastrointestinal tract of newborns, mild digestive problems, such as inefficient digestion and impaired absorption of proteins, lipids and lactose, and gut dysbiosis, are often seen in infancy. The differences in composition between infant formula and human milk make mild digestive problems more likely to occur in formula-fed infants. In recent years, several types of infant formulas have been developed to treat or reduce gastrointestinal digestive problems in infants. This review summarizes the gastrointestinal environment of infants and the digestion of human milk and different infant formulas. We particularly focus on the common digestive problems and appropriate nutritional solutions that may occur in healthy term infants during the first six months of life.

Gastrointestinal Dysfunction in Parkinson's Disease.

There has been exponential growth in the awareness and understanding of gastrointestinal (GI) dysfunction in Parkinson's disease (PD) over the past 3 decades. The clinical features of GI dysfunction in PD have been clearly identified and innovative research has demonstrated the presence of pathology within the enteric nervous system (ENS) in individuals with PD, leading to suggestions that the GI system may be ground zero for the genesis and the portal of entry of PD pathology, which then ascends via the vagus nerve to the central nervous system (CNS). This theory, as well as the more recent recognition of the association of PD with dysbiosis within the gut microbiota, has been the object of intense study and scrutiny. Since most PD medications are absorbed through the GI system, the need for better understanding of changes within the GI tract that may potentially affect the pattern of response to medications has become evident. In this review, current knowledge of the pathophysiology of changes within the GI tract and the gut microbiome of individuals with PD, including changes that occur with progression of the disease, will be addressed. We focus on common clinical GI problems in PD that can arise from different segments of the GI tract. Relevant diagnostic evaluations and treatment options for each of these problems will be reviewed.

Gastrointestinal Dysfunction Criteria in Critically Ill Children: The PODIUM Consensus Conference.

CONTEXT: Prior criteria to define pediatric multiple organ dysfunction syndrome (MODS) did not include gastrointestinal dysfunction. OBJECTIVES: Our objective was to evaluate current evidence and to develop consensus criteria for gastrointestinal dysfunction in critically ill children. DATA SOURCES: Electronic searches of PubMed and EMBASE were conducted from January 1992 to January 2020, using medical subject heading terms and text words to define gastrointestinal dysfunction, pediatric critical illness, and outcomes. STUDY SELECTION: Studies were included if they evaluated critically ill children with gastrointestinal dysfunction, performance characteristics of assessment/scoring tools to screen for gastrointestinal dysfunction, and assessed outcomes related to mortality, functional status, organ-specific outcomes, or other patient-centered outcomes. Studies of adults or premature infants, animal studies, reviews/commentaries, case series with sample size ≤10, and non-English language studies with inability to determine eligibility criteria were excluded. DATA EXTRACTION: Data were abstracted from each eligible study into a standard data extraction form along with risk of bias assessment by a task force member. RESULTS: The systematic review supports the following criteria for severe gastrointestinal dysfunction: 1a) bowel perforation, 1b) pneumatosis intestinalis, or 1c) bowel ischemia, present on plain abdominal radiograph, computed tomography (CT) scan, magnetic resonance imaging (MRI), or gross surgical inspection, or 2) rectal sloughing of gut mucosa. LIMITATIONS: The validity of the consensus criteria for gastrointestinal dysfunction are limited by the quantity and quality of current evidence. CONCLUSIONS: Understanding the role of gastrointestinal dysfunction in the pathophysiology and outcomes of MODS is important in pediatric critical illness.

Patient reported outcomes for cisplatin and radiation followed by carboplatin/paclitaxel versus carboplatin/paclitaxel for locally advanced endometrial carcinoma: An NRG oncology study.

INTRODUCTION: Chemotherapy plus radiation (Cis-RT + CP) did not demonstrate superiority in prolonging relapse-free survival compared to chemotherapy alone in patients with stage III or IVA endometrial carcinoma. The impact of treatment on quality of life (QOL), neurotoxicity (NTX) and psychometric properties of the gastrointestinal (GI) symptoms subscale during treatment and up to 1 year are described herein. METHODS: QOL assessments were scheduled at baseline, 6 weeks (post completion of RT (Cis-RT + CP) or prior to cycle 3 (CP)), then 18 weeks (end of treatment) and 70 weeks (1 year after the end of treatment) after starting treatment. QOL instruments included the FACT-En TOI, FACT/GOG-neurotoxicity (Ntx) subscale (short), and the gastrointestinal (GI) symptoms subscale. RESULTS: At the end of treatment, patients receiving Cis-RT + CP reported a statistically significant decreased QOL when compared to CP. The decline in QOL was reflected in physical well-being, functional well-being, and endometrial cancer specific concerns, but the minimally important differences (MID) were not considered clinically meaningful. Patients in both groups reported increased chemotherapy-induced Ntx symptoms with the CP group having worse scores and reaching peak symptoms at the time of chemotherapy completion. Patients on Cis-RT + CP reported statistically significantly worse GI symptoms after radiation therapy compared to patients on CP, this occurred across assessment intervals, though the MID was not meaningful. Psychometric evaluations indicated that the GI symptom scale is reliable, valid, and responsive to change. CONCLUSIONS: PROs indicate that the chemoradiotherapy group experienced worse HRQoL and GI toxicity compared to patients randomized to chemotherapy alone for locally advanced endometrial cancer though based on the MID, these were not clinically meaningful differences. The GI symptom subscale was a reliable and valid scale that has value for future trials. TRIAL REGISTRATION: NCT00942357.

Sex Moderates the Relationship Between Nausea Severity and Heart Rate Variability in Adolescents and Young Adults.

BACKGROUND: Nausea is a common complaint among children and is particularly prevalent in children with functional abdominal pain (FAP), with nearly half of children with FAP also endorsing nausea. Dysfunction of the autonomic nervous system, which can be indexed by heart rate variability (HRV), leads to abnormalities in gastric electrical activity that are associated with GI symptoms. AIMS: To evaluate that relationship between nausea severity and HRV in adolescents and young adults with a history of FAP and to assess for sex differences. METHODS: Participants were pediatric patients with a diagnosis of FAP who were recruited from a pediatric GI clinic between 1993 and 2007 for a prospective study of the course of FAP. Study analyses focused on the cross-sectional relationship between HRV, indexed by standard deviation of the R-R interval (SDRRI) and high-frequency (HF) power, and nausea severity collected during a follow-up visit in late adolescence and young adulthood. RESULTS: Controlling for age and BMI, a significant nausea by sex interaction emerged for both SDRRI and HF power. Tests of conditional effects of nausea by sex showed that the inverse relation between nausea severity and both SDRRI and HF was significant for females but not for males. CONCLUSIONS: This is the first study to evaluate the relationship between nausea severity and HRV. Greater nausea severity was associated with lower HRV in females but not in males. Further validation of these results may provide insight into novel treatment approaches for females with nausea that target vagal tone.

Centrally Administered Neuropeptide-S Alleviates Gastrointestinal Dysmotility Induced by Neonatal Maternal Separation.

BACKGROUND: Neuropeptide-S (NPS) regulates autonomic outflow, stress response, and gastrointestinal (GI) motor functions. This study aimed to investigate the effects of NPS on GI dysmotility induced by neonatal maternal separation (MS). METHODS: MS was conducted by isolating newborn pups from dams from postnatal day 1 to day 14. In adulthood, rats were also exposed to chronic homotypic stress (CHS). Visceral sensitivity was assessed by colorectal distension-induced abdominal contractions. Gastric emptying (GE) was measured following CHS, whereas fecal output was monitored daily. NPS or NPS receptor (NPSR) antagonist was centrally applied simultaneously with electrocardiography and gastric motility recording. Immunoreactivities for NPS, NPSR, corticotropin-releasing factor (CRF), choline acetyltransferase (ChAT), tyrosine hydroxylase (TH), and c-Fos were assessed by immunohistochemistry. KEY RESULTS: NPS alleviated the MS-induced visceral hypersensitivity. Under basal conditions, central exogenous or endogenous NPS had no effect on GE and gastric motility. NPS restored CHS-induced gastric and colonic dysmotility in MS rats while increasing sympatho-vagal balance without affecting vagal outflow. NPSR expression was detected in CRF-producing cells of hypothalamic paraventricular nucleus, and central amygdala, but not in Barrington's nucleus. Moreover, NPSR was present in ChAT-expressing neurons in dorsal motor nucleus of the vagus (DMV), and nucleus ambiguus (NAmb) in addition to the TH-positive neurons in C1/A1, and locus coeruleus (LC). Neurons adjacent to the adrenergic cells in LC were found to produce NPS. NPS administration caused c-Fos expression in C1/A1 cells, while no immunoreactivity was detected in DMV or NAmb. CONCLUSIONS: NPS/NPSR system might be a novel target for the treatment of stress-related GI dysmotility.

A Rome Working Team Report on Brain-Gut Behavior Therapies for Disorders of Gut-Brain Interaction.

BACKGROUND AND AIMS: This Rome Foundation Working Team Report reflects the consensus of an international interdisciplinary team of experts regarding the use of behavioral interventions, specifically brain-gut behavior therapies (BGBTs), in patients with disorders of gut-brain interaction (DGBIs). METHODS: The committee members reviewed the extant scientific literature and, when possible, addressed gaps in this literature through the lens of their clinical and scientific expertise. The Delphi method was used to create consensus on the goals, structure, and framework before writing the report. The report is broken into 5 parts: 1) definition and evidence for BGBT, 2) the gut-brain axis as the mechanistic basis for BGBT, 3) targets of BGBTs, 4) common and unique therapeutic techniques seen in BGBT, and 5) who and how to refer for BGBT. RESULTS: We chose to not only review for the reader the 5 existing classes of BGBT and their evidence, but to connect DGBI-specific behavioral targets and techniques as they relate directly, or in some cases indirectly, to the gut-brain axis. In doing so, we expect to increase gastrointestinal providers' confidence in identifying and referring appropriate candidates for BGBT and to support clinical decision making for mental health professionals providing BGBT. CONCLUSIONS: Both gastrointestinal medical providers and behavioral health providers have an opportunity to optimize care for DGBIs through a collaborative integrated approach that begins with an effective patient-provider relationship, thoughtful communication about the brain-gut axis and, when appropriate, a well communicated referral to BGBT.

Association between breakfast consumption frequency and the risk of irritable bowel syndrome among Chinese female college students: A cross-sectional study.

ABSTRACT: Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder that affects specific groups of people. The relationship between breakfast consumption frequency and the risk of IBS is unclear. This study aimed to investigate the association between breakfast consumption frequency and the risk of IBS among Chinese female college students.In this cross-sectional study (n = 706) conducted in October 2018, the frequency of breakfast consumption was categorized as 0 to 3 times/week, 4 to 6 times/week, or daily. IBS was diagnosed according to the Rome III criteria and was based on the presence of abdominal pain or discomfort for at least 3 months during the previous 6 months, with at least 2 or more of the following conditions: changes in frequency or form of stool and/or decrease in pain after defecation. We adjusted for confounding factors, including age, only child (yes or no), parents' educational levels (senior high school or below, college, or postgraduate), parents' marital status (married, widowed, or divorced), smoking status (smoker or nonsmoker), drinking status (drinker or nondrinker), body mass index, and depressive symptoms. A multiple logistic regression analysis was performed to determine the relationship between breakfast frequency and the risk of IBS.Among 706 participants, 23.7% were the only child in their family, and the proportion of parents divorced or widowed was 18.5%. The proportion of fathers and mothers with high school education or above was 93.3% and 96.3%, respectively. The prevalence of IBS among the participants was 17.3% (122/706). Multivariate logistic regressions analysis showed that breakfast consumption frequency is negatively associated with the risk of IBS after adjusting for confounding factors. The odds ratios (95% confidence intervals) for IBS in the breakfast frequency category of 0 to 3 times/week, 4 to 6 times/week, and daily were 1.00 (reference), 0.96 (0.58, 1.60), and 0.45 (0.26, 0.78), respectively (P = .002).Our data revealed that regular breakfast consumption is associated with a lower risk of IBS among Chinese college students. Future cohort and/or interventional studies should be conducted to further explore the association between breakfast consumption frequency and IBS.

Oropharyngeal Dysphagia and Impaired Motility of the Upper Gastrointestinal Tract-Is There a Clinical Link in Neurocritical Care?

Patients in the neurological ICU are at risk of suffering from disorders of the upper gastrointestinal tract. Oropharyngeal dysphagia (OD) can be caused by the underlying neurological disease and/or ICU treatment itself. The latter was also identified as a risk factor for gastrointestinal dysmotility. However, its association with OD and the impact of the neurological condition is unclear. Here, we investigated a possible link between OD and gastric residual volume (GRV) in patients in the neurological ICU. In this retrospective single-center study, patients with an episode of mechanical ventilation (MV) admitted to the neurological ICU due to an acute neurological disease or acute deterioration of a chronic neurological condition from 2011-2017 were included. The patients were submitted to an endoscopic swallowing evaluation within 72 h of the completion of MV. Their GRV was assessed daily. Patients with ≥1 d of GRV ≥500 mL were compared to all the other patients. Regression analysis was performed to identify the predictors of GRV ≥500 mL/d. With respect to GRV, the groups were compared depending on their FEES scores (0-3). A total of 976 patients were included in this study. A total of 35% demonstrated a GRV of ≥500 mL/d at least once. The significant predictors of relevant GRV were age, male gender, infratentorial or hemorrhagic stroke, prolonged MV and poor swallowing function. The patients with the poorest swallowing function presented a GRV of ≥500 mL/d significantly more often than the patients who scored the best. Conclusions: Our findings indicate an association between dysphagia severity and delayed gastric emptying in critically ill neurologic patients. This may partly be due to lesions in the swallowing and gastric network.

Influence of Tilia tomentosa Moench Extract on Mouse Small Intestine Neuromuscular Contractility.

Functional gastrointestinal disorders (FGIDs) are characterized by abdominal pain, bloating and bowel disturbances. FGID therapy is primarily symptomatic, including treatment with herbal remedies. Flower extract of Tilia tomentosa Moench (TtM) is occasionally used as an anti-spasmodic in popular medicine. Since its effect on intestinal response is unknown, we evaluated the influence of TtM extract on small intestine contractility. Ileal preparations from C57BL/6J mice were mounted in organ baths to assess changes in muscle tension, following addition of TtM extract (0.5-36 µg/mL) or a vehicle (ethanol). Changes in contractile response to receptor- and non-receptor-mediated stimuli were assessed in ileal preparations pretreated with 12 µg/mL TtM. Alterations in the enteric nervous system neuroglial network were analyzed by confocal immunofluorescence. Increasing addition of TtM induced a marked relaxation in ileal specimens compared to the vehicle. Pretreatment with TtM affected cholinergic and tachykininergic neuromuscular contractions as well as K+-induced smooth muscle depolarization. Following incubation with TtM, a significant reduction in non-adrenergic non-cholinergic-mediated relaxation sensitive to Nω-Nitro-L-arginine methyl ester hydrochloride (pan-nitric oxide synthase inhibitor) was found. In vitro incubation of intestinal specimens with TtM did not affect the myenteric plexus neuroglial network. Our findings show that TtM-induced intestinal relaxation is mediated by nitric oxide pathways, providing a pharmacological basis for the use of TtM in FGIDs.

Infants with cystic fibrosis have altered fecal functional capacities with potential clinical and metabolic consequences.

BACKGROUND: Infants with cystic fibrosis (CF) suffer from gastrointestinal (GI) complications, including pancreatic insufficiency and intestinal inflammation, which have been associated with impaired nutrition and growth. Recent evidence identified altered fecal microbiota taxonomic compositions in infants with CF relative to healthy infants that were characterized by differences in the abundances of taxa associated with GI health and nutrition. Furthermore, these taxonomic differences were more pronounced in low length infants with CF, suggesting a potential link to linear growth failure. We hypothesized that these differences would entail shifts in the microbiome's functional capacities that could contribute to inflammation and nutritional failure in infants with CF. RESULTS: To test this hypothesis, we compared fecal microbial metagenomic content between healthy infants and infants with CF, supplemented with an analysis of fecal metabolomes in infants with CF. We identified notable differences in CF fecal microbial functional capacities, including metabolic and environmental response functions, compared to healthy infants that intensified during the first year of life. A machine learning-based longitudinal metagenomic age analysis of healthy and CF fecal metagenomic functional profiles further demonstrated that these differences are characterized by a CF-associated delay in the development of these functional capacities. Moreover, we found metagenomic differences in functions related to metabolism among infants with CF that were associated with diet and antibiotic exposure, and identified several taxa as potential drivers of these functional differences. An integrated metagenomic and metabolomic analysis further revealed that abundances of several fecal GI metabolites important for nutrient absorption, including three bile acids, correlated with specific microbes in infants with CF. CONCLUSIONS: Our results highlight several metagenomic and metabolomic factors, including bile acids and other microbial metabolites, that may impact nutrition, growth, and GI health in infants with CF. These factors could serve as promising avenues for novel microbiome-based therapeutics to improve health outcomes in these infants.

Gastrointestinal problems, mechanisms and possible therapeutic directions in Gulf war illness: a mini review.

By its nature, Gulf war illness (GWI) is multisymptomatic and affects several organ systems in the body. Along with other symptoms, veterans who suffer from GWI commonly report chronic gastrointestinal issues such as constipation, pain, indigestion, etc. However, until recently, most attention has been focused on neurological disturbances such as cognitive impairments, chronic fatigue, and chronic pain among affected veterans. With such high prevalence of gastrointestinal problems among Gulf war (GW) veterans, it is surprising that there is little research to investigate the mechanisms behind these issues. This review summarizes all the available works on the mechanisms behind gastrointestinal problems in GWI that have been published to date in various databases. Generally, these studies, which were done in rodent models, in vitro and human cohorts propose that an altered microbiome, a reactive enteric nervous system or a leaky gut among other possible mechanisms are the major drivers of gastrointestinal problems reported in GWI. This review aims to draw attention to the gastrointestinal tract as an important player in GWI disease pathology and a potential therapeutic target.

Gastric accommodation: Physiology, diagnostic modalities, clinical relevance, and therapies.

BACKGROUND: Gastric accommodation is an essential gastric motor function which occurs following ingestion of a meal. Impaired gastric fundic accommodation (IFA) is associated with dyspeptic symptoms. Gastric accommodation is mediated by the vagal pathway with several important physiologic factors such as duodenal nutrient feedback playing a significant role. IFA has been described as a pathophysiologic factor in several gastrointestinal disorders including functional dyspepsia, diabetic gastropathy, post-Nissen fundoplication, postsurgical gastrectomy, and rumination syndrome. Modalities for gastric accommodation assessment include gastric barostat, intragastric meal distribution via scintigraphy, drinking tests (eg, water load), SPECT, MRI, 2D and 3D ultrasound, and intragastric high-resolution manometry. Several treatment options including sumatriptan, buspirone, tandospirone, ondansetron, and acotiamide may improve symptoms by increasing post-meal gastric volume. PURPOSE: Our aim is to provide an overview of the physiology, diagnostic modalities, and therapies for IFA. A literature search was conducted on PubMed, Google Scholar, and other sources to identify relevant studies available until December 2020. Gastric accommodation is an important gastric motor function which if impaired, is associated with several upper gastrointestinal disorders. There are an increasing number of gastric accommodation testing modalities; however, each has facets which warrant consideration. Evidence regarding potentially effective therapies for IFA is growing.

Bilateral Subthalamic Nucleus Deep Brain Stimulation Improves Gastric Emptying Time in Parkinson Disease.

BACKGROUND: It is well-established that deep brain stimulation (DBS) can improve motor function in those with Parkinson disease (PD); however, its effects on gastrointestinal disorders remain unclear. METHODS: From January 2019 to December 2020, 26 patients with PD who had undergone subthalamic nucleus (STN) DBS were included in our study. The evaluated items included the pre- and postoperative dose of levodopa, Unified Parkinson's Disease Rating Scale, part III, scores with and without medication and stimulation, and gastric emptying time (expressed as the peak time of carbon-13C dioxide excretion in the 13C-acetate breath test). Sex-, age-, and body weight-matched controls were recruited to test the gastric emptying time in healthy individuals. RESULTS: All the patients benefited from DBS. The Unified Parkinson's Disease Rating Scale, part III, scores had decreased from 48.5 ± 13.77 to 25.23 ± 8.59 without medication and 31.23 ± 11.4 to 13.92 ± 5.27 with medication. The levodopa equivalent dose had decreased from 1009.8 ± 291 mg to 707.65 ± 193.79 mg. The gastric emptying time was significantly prolonged in the patients with PD before DBS compared with the healthy control group (29.23 ± 6.58 minutes) and had improved to 35.19 ± 10.14 minutes with medication and 38.07 ± 11.17 minutes without medication after 3 months of STN stimulation. At 6 months postoperatively, the gastric emptying time was 32.3 ± 10.02 minutes without medication and 33.84 ± 10.79 minutes with medication. CONCLUSIONS: A delayed gastric emptying time is associated with greater PD severity. Antiparkinsonian medications did not affect gastric emptying in patients with PD. STN DBS can improve both movement function and gastrointestinal motility in patients with PD in the long term. The exact mechanism by which DBS improves gastric emptying requires further exploration.

Lymphopenia in hospitalized patients and its relationship with severity of illness and mortality.

BACKGROUND: Lymphopenia is associated with various pathologies such as sepsis, burns, trauma, general anesthesia and major surgeries. All these pathologies are clinically expressed by the so-called Systemic Inflammatory Response Syndrome which does not include lymphopenia into defining criteria. The main objective of this work was to analyze the diagnosis of patients admitted to a hospital related to lymphopenia during hospital stay. In addition, we investigated the relationship of lymphopenia with the four levels of the Severity of Illness (SOI) and the Risk of Mortality (ROM). METHOD AND FINDINGS: Lymphopenia was defined as Absolute Lymphocyte Count (ALC) <1.0 x109/L. ALC were analyzed every day since admission. The four levels (minor, moderate, major and extreme risk) of both SOI and ROM were assessed. A total of 58,260 hospital admissions were analyzed. More than 41% of the patients had lymphopenia during hospital stay. The mean time to death was shorter among patients with lymphopenia on admission 65.6 days (CI95%, 57.3-73.8) vs 89.9 (CI95%, 82.4-97.4), P<0.001. Also, patients with lymphopenia during hospital stay had a shorter time to the mortality, 67.5 (CI95%, 61.1-73.9) vs 96.9 (CI95%, 92.6-101.2), P<0.001. CONCLUSIONS: Lymphopenia had a high prevalence in hospitalized patients with greater relevance in infectious pathologies. Lymphopenia was related and clearly predicts SOI and ROM at the time of admission, and should be considered as clinical diagnostic criteria to define SIRS.

Sex differences feed into nuclear receptor signaling along the digestive tract.

Sex differences in physiology are noted in clinical and animal studies. However, mechanisms underlying these observed differences between males and females remain elusive. Nuclear receptors control a wide range of physiological pathways and are expressed in the gastrointestinal tract, including the mouth, stomach, liver and intestine. We investigated the literature pertaining to ER, AR, FXR, and PPAR regulation and highlight the sex differences in nutrient metabolism along the digestive system. We chose these nuclear receptors based on their metabolic functions, and hormonal actions. Intriguingly, we noted an overlap in target genes of ER and FXR that modulate mucosal integrity and GLP-1 secretion, whereas overlap in target genes of PPARα with ER and AR modulate lipid metabolism. Sex differences were seen not only in the basal expression of nuclear receptors, but also in activation as their endogenous ligand concentrations fluctuate depending on nutrient availability. Finally, in this review, we speculate that interactions between the nuclear receptors may influence overall metabolic decisions in the gastrointestinal tract in a sex-specific manner.