THE EFFECT OF ENTERAL LACTOFERRIN SUPPLEMENTATION IN PREVENTION OF MORBIDITY ASSOCIATED WITH IMMATURE DIGESTIVE TRACT IN PREMATURE INFANTS: PROSPECTIVE COHORT STUDY.

Premature infants are at high risk for diseases associated with impaired adaptation of the immature digestive tract, such as necrotizing enterocolitis (NEC) or late-onset sepsis (LOS), as well as severe neonatal morbidities associated with these diseases. This study was aimed to evaluate the effectiveness of prophylactic enteral use of bovine lactoferrin for the prevention of severe neonatal diseases in premature infants. The prospective cohort study included 117 premature infants with gestational age (GA) of ≤32 weeks, a birth weight of ≤1,500 g, and an age of ≤72 hours. 27 infants who were receiving enteral feeds were randomized to receive lactoferrin at a dose of 100 mg/day until postmenstrual age (PMA) of 36 weeks or discharge (at least 4 weeks). 90 infants formed the control group and received standard treatment. The primary outcome was the incidence of LOS, the secondary outcomes were the incidence of necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), severe brain damage, bronchopulmonary dysplasia (BPD), overall mortality, as well as the age of achieving full enteral feeds, duration of antibacterial therapy, length of stay in NICU and the total length of hospital stay. Enteral lactoferrin supplementation did not reduce the incidence of LOS (29.6% in the lactoferrin group against 22.7% in the control group; p=0.85), NEC (5.6% vs. 1.8%, respectively; p=0.11) and overall mortality (18.5% vs. 9.1%, respectively; p=0.06), as well as the incidence of severe intraventricular hemorrhages (18.5% vs. 9.8%, respectively; p=0.17), PVL (11.1% vs. 2.2%, respectively; p=0.17) and BPD (14.8% vs. 25.6%, respectively; p = 0.25). Infants receiving lactoferrin were achieving full enteral feeds significantly faster compared to the control group (14 (10-17) days vs. 19 (13-32) days, respectively; p=0.007). The total length of hospital stay of infants with GA ≤28 weeks in the lactoferrin group was significantly shorter compared to the control group (74 (68-89) vs. 98 (83-109) days, respectively; p=0.048). Enteral lactoferrin supplementation at a dose of 100 mg/day does not affect the main morbidity and mortality of prematurely born infants with GA ≤ 32 weeks but may facilitate significantly faster achievement of the full enteral feeds and the reduction of the length of hospital stay in the tiniest infants.

Are We What We Eat? Impact of Diet on the Gut-Brain Axis in Parkinson's Disease.

Parkinson's disease is characterized by motor and non-motor symptoms, such as defects in the gut function, which may occur before the motor symptoms. To date, there are therapies that can improve these symptoms, but there is no cure to avoid the development or exacerbation of this disorder. Dysbiosis of gut microbiota could have a crucial role in the gut-brain axis, which is a bidirectional communication between the central nervous system and the enteric nervous system. Diet can affect the microbiota composition, impacting gut-brain axis functionality. Gut microbiome restoration through probiotics, prebiotics, synbiotics or other dietary means could have the potential to slow PD progression. In this review, we will discuss the influence of diet on the bidirectional communication between gut and brain, thus supporting the hypothesis that this disorder could begin in the gut. We also focus on how food-based therapies might then have an influence on PD and could ameliorate non-motor as well as motor symptoms.

Impact of STIMUlant and osmotic LAXatives (STIMULAX trial) on gastrointestinal recovery after colorectal surgery: randomized clinical trial.

BACKGROUND: Recovery of gastrointestinal (GI) function is often delayed after colorectal surgery. Enhanced recovery protocols (ERPs) recommend routine laxative use, but evidence of benefit is unclear. This study aimed to investigate whether the addition of multimodal laxatives to an ERP improves return of GI function in patients undergoing colorectal surgery. METHODS: This was a single-centre, parallel, open-label RCT. All adult patients undergoing elective colorectal resection or having stoma formation or reversal at the Royal Adelaide Hospital between August 2018 and May 2020 were recruited into the study. The STIMULAX group received oral Coloxyl® with senna and macrogol, with a sodium phosphate enema in addition for right-sided operations. The control group received standard ERP postoperative care. The primary outcome was GI-2, a validated composite measure defined as the interval from surgery until first passage of stool and tolerance of solid intake for 24 h in the absence of vomiting. Secondary outcomes were the incidence of prolonged postoperative ileus (POI), duration of hospital stay, and postoperative complications. The analysis was performed on an intention-to-treat basis. RESULTS: Of a total of 170 participants, 85 were randomized to each group. Median GI-2 was 1 day shorter in the STIMULAX compared with the control group (median 2 (i.q.r. 1.5-4) versus 3 (2-5.5) days; 95 per cent c.i. -1 to 0 days; P = 0.029). The incidence of prolonged POI was lower in the STIMULAX group (22 versus 38 per cent; relative risk reduction 42 per cent; P = 0.030). There was no difference in duration of hospital day or 30-day postoperative complications (including anastomotic leak) between the STIMULAX and control groups. CONCLUSION: Routine postoperative use of multimodal laxatives after elective colorectal surgery results in earlier recovery of gastrointestinal function and reduces the incidence of prolonged POI. Registration number: ACTRN12618001261202 (www.anzctr.org.au).

Acupoint Massage Can Effectively Promote the Recovery of Gastrointestinal Function after Gynecologic Laparoscopy.

Objective: To investigate the effect of acupoint massage on the recovery of gastrointestinal function in patients after laparoscopic surgery for gynecologic indications. Methods: A total of 160 patients, who underwent gynecologic laparoscopy from December 2015 to January 2017, were recruited. Half of the patients received standard postoperative nursing (i.e., the control group); while the other half received acupoint massage in addition to the standard care (i.e., the observation group). The recovery time of bowel sounds, the first anal exhaust time and the first defecation time were recorded. The plasma levels of motilin, somatostatin and cholecystokinin before and after the surgery were also determined. Results: Compared to the control group, the observation group demonstrated significantly shorter bowel sound recovery time, first anal exhaust time and first defecation time (t = 11.755, 10.400, 11.950, P < 0.01 for all comparisons). Before surgery, the plasma levels of gastrointestinal hormones in both groups were comparable. At 12, 24, and 48 hours postoperative, the difference between two groups was statistically significant (P < 0.05). The overall response rate of the observation group was also significantly higher than that of the control group (control group, 78.75%; observation group, 97.50%; P = 0.008). Conclusion: Acupoint massage could accelerate the recovery of bowel function after gynecologic laparoscopy by modulating the release of gastrointestinal hormones.

Berberine reduces gut-vascular barrier permeability via modulation of ApoM/S1P pathway in a model of polymicrobial sepsis.

AIMS: The hyperpermeability of gut-vascular barrier (GVB) plays a role in gut-derived sepsis. The goal of this study was to evaluate if berberine might improve hepatic apolipoprotein M (ApoM) generation and raise plasma ApoM level to protect the compromised GVB. MATERIALS AND METHODS: The compromised GVB was induced by sepsis. Hepatic ApoM mRNA and phosphoenolpyruvate carboxykinase (PEPCK) mRNA and plasma ApoM level were assayed by qRT-PCR and ELISA, respectively. The permeability of intestinal capillary in vivo and of rat intestinal microvascular endothelial cells (RIMECs) in vitro was assayed by FITC-dextran. The blood glucose was detected by a glucometer. Plasma insulin, TNF-α and IL-1ß were assayed by ELISA. The plasmalemma vesicle-associated protein-1 (PV1), ß-catenin and occludin in RIMECs were assayed by Western blot. KEY FINDINGS: Sepsis decreased hepatic ApoM mRNA and plasma ApoM level, but raised hepatic PEPCK mRNA and plasma glucose, insulin, TNF-α, and IL-1ß levels. The increased vascular endothelial permeability was abrogated by recombinant rat ApoM in vivo or ApoM-bound S1P in vitro. ApoM-bound S1P decreased PV1 but increased occludin and ß-catenin expression in LPS-treated RIMECs. Berberine in a dose-dependent manner raised hepatic ApoM mRNA and plasma ApoM level, but decreased septic hyperglycemia, insulin resistance and plasma TNF-α and IL-1ß levels. Berberine reduced sepsis-induced PEPCK and TLR4 mRNA overexpression in the liver. SIGNIFICANCE: This study demonstrated berberine inhibited TLR4-mediated hyperglycemia, insulin resistance and proinflammatory molecule production, thereby increasing ApoM gene expression and plasma ApoM. Berberine protected the damaged GVB via modulation of ApoM/S1P pathway.

Gastrointestinal Tolerance of Low, Medium and High Dose Acute Oral l-Glutamine Supplementation in Healthy Adults: A Pilot Study.

l-Glutamine (GLN) is a conditionally essential amino acid which supports gastrointestinal (GI) and immune function prior to catabolic stress (e.g., strenuous exercise). Despite potential dose-dependent benefits, GI tolerance of acute high dose oral GLN supplementation is poorly characterised. Fourteen healthy males (25 ± 5 years; 1.79 ± 0.07 cm; 77.7 ± 9.8 kg; 14.8 ± 4.6% body fat) ingested 0.3 (LOW), 0.6 (MED) or 0.9 (HIGH) g·kg·FFM-1 GLN beverages, in a randomised, double-blind, counter-balanced, cross-over trial. Individual and accumulated GI symptoms were recorded using a visual analogue scale at regular intervals up to 24-h post ingestion. GLN beverages were characterised by tonicity measurement and microscopic observations. 24-h accumulated upper- and lower- and total-GI symptoms were all greater in the HIGH, compared to LOW and MED trials (p < 0.05). Specific GI symptoms (discomfort, nausea, belching, upper GI pain) were all more pronounced on the HIGH versus LOW GLN trial (p < 0.05). Nevertheless, most symptoms were still rated as mild. In comparison, the remaining GI symptoms were either comparable (flatulence, urge to regurgitate, bloating, lower GI pain) or absent (heart burn, vomiting, urge to defecate, abnormal stools, stitch, dizziness) between trials (p > 0.05). All beverages were isotonic and contained a dose-dependent number of GLN crystals. Acute oral GLN ingestion in dosages up to 0.9 g·kg·FFM-1 are generally well-tolerated. However, the severity of mild GI symptoms appeared dose-dependent during the first two hours post prandial and may be due to high-concentrations of GLN crystals.

[Effect of acupoint application therapy at different timing points on gastrointestinal function recovery and heart rate variability after laparoscopic resection of colorectal cancer].

OBJECTIVE: To observe the effect of acupoint application therapy at different timing points on the gastrointestinal function recovery and heart rate variability (HRV) after laparoscopic resection of colorectal cancer under the instruction of enhanced recovery after surgery (ERAS). METHODS: A total of 105 patients for the selective laparoscopic resection of colorectal cancer were selected and randomized into a preoperative acupoint application group (35 cases, 3 cases dropped off), a postoperative acupoint application group (35 cases, 1 case dropped out) and a control group (35 cases, 2 cases dropped off). In the control group, ERAS interventions were provided, such as health education, fluid supplementation and multi-mode analgesia. On the base of the treatment as the control group, in the preoperative acupoint application group and the postoperative acupoint application group, 3 days before operation and 6 h after operation, the acupoint application therapy was given respectively. The acupoints were Zusanli (ST 36), Shangjuxu (ST 37), Sanyinjiao (SP 6), Neiguan (PC 6) and Xiajuxu (ST 39). The acupoint application was exerted for 6 h each time, once daily till the first postoperative exhaust and defecation presented. It was to observe the time of the first postoperative exhaust, defecation and food intake, the score of visual analogue scale (VAS) 1 to 3 days after operation, the total score of gastrointestinal symptom rating scale (GSRS) before and 1 week after operation, as well as the related indicators of HRV [standard deviation of NN intervals (SDNN) and the ratio of low-frequency power and high frequency power (LF/HF)] in the three groups successively. Besides, the adverse reactions were recorded during intervention in the three groups. RESULTS: Compared with the control group, the time of the first postoperative exhaust and the time of the first postoperative defecation were all earlier in the preoperative acupoint application group and the postoperative acupoint application group respectively (P<0.05), and VAS scores 1 to 3 days after operation and total GSRS scores 1 week after operation were all reduced (P<0.05); the time of first food intake was earlier after operation (P<0.05), and SDNN and LF/LF were increased 1 day and 3 days after operation in the preoperative acupoint application group (P<0.05). Compared with the postoperative acupoint application group, in the preoperative acupoint application group, the time of the first postoperative exhaust and the time of the first postoperative defecation were all earlier (P<0.05), VAS scores were reduced in 1 to 3 days after operation (P<0.05), and SDNN 1 day and 3 days after operation and LF/HF 1 day after operation were all increased (P<0.05). No adverse reaction was detected in patients of the three groups. CONCLUSION: Under the instruction of ERAS, the preoperative acupoint application effectively promotes the postoperative gastrointestinal function recovery, improves HRV and autonomous nerve function in the patients after laparoscopic resection of colorectal cancer. The therapeutic effect of this therapy is better than the postoperative acupoint application.

Postural Tachycardia Syndrome: Nutrition Implications.

Postural tachycardia syndrome (POTS) is a syndrome characterized by elevated heart rate without hypotension and most commonly occurs in young females (generally <35 years of age). The prevalence of POTS is on the rise, but the etiology is still under investigation, and there appear to be multiple potential physiologic causes. The majority of these patients experience a multitude of gastrointestinal (GI) and systemic symptoms and conditions that may contribute to functional debility and poor quality of life. Although symptoms generally improve with age, they can still lead to significant issues meeting nutrition and hydration needs. This paper summarizes the understood potential pathophysiology of POTS, associated GI and nutrition issues, general treatment of POTS, and strategies to assess and meet the unique nutrition and hydration needs of these patients.

Effects of Endovascular Stent-Assisted Effects of Various Frequencies of Abdominal Naprapathy on Changes in Gastrointestinal Mucosal Cells in Spleen-Deficient Rabbits.

BACKGROUND At certain frequencies, abdominal naprapathy effectively alleviates functional dyspepsia with spleen deficiency. The present study explored the effects of various frequencies of abdominal naprapathy on gastrointestinal mucosal cells in spleen-deficient rabbits. MATERIAL AND METHODS The model of spleen deficiency was established by the method of bitter cold and catharsis. The rabbits were treated with various frequencies (50 - 100 and 201 - 250 vibrations/min) of abdominal naprapathy.  RESULTS In model rabbits, gastrointestinal mucosal thickness was changed, mucosal epithelial cells were necrotic significantly, a large number of inflammatory cells were infiltrated, and duodenal villus were destroyed. The gastrointestinal mucosal cells had different degrees of regeneration and remodeling under various frequencies of abdominal naprapathy intervention. Among them, the abdominal naprapathy with manipulation frequency of 101 - 150 times/min showed the best effect. CONCLUSIONS The abdominal naprapathy, especially with frequency of 101~150 times/min, repairs gastrointestinal mucosal injury of spleen-deficiency rabbits.

Purgative/laxative actions of Globularia alypum aqueous extract on gastrointestinal-physiological function and against loperamide-induced constipation coupled to oxidative stress and inflammation in rats.

BACKGROUND: Chronic constipation is a gastrointestinal functional disorder which affects patient quality of life. Therefore, many studies were oriented to search herbal laxative agents. In this study, we investigated the effect of Globularia alypum L. leaves aqueous extract (GAAE) against loperamide (LOP)-produced constipation. METHODS: Animals were given LOP (3 mg/kg, b.w., i.p.) and GAAE (100, 200, and 400 mg/kg, b.w., p.o.) or yohimbine (2 mg/kg, b.w., i.p.), simultaneously, for 1 week. Gastric-emptying test and intestinal transit were determined. Colon histology was examined, and oxidative status was evaluated using biochemical-colorimetric methods. KEY RESULTS: GAAE ameliorates significantly gastric emptying (64% to 76.5%) and intestinal transit (66.65% to 84.73%). LOP negatively influenced defecation parameters and generated a stress situation. GAAE administration in contrast ameliorated those parameters and re-established oxidative balance. CONCLUSION: GAAE showed a modest action against oxidative stress and decreased LOP effect and thereby can be considered a pharmacological agent in constipation.

Dietary Phytochemicals as Neurotherapeutics for Autism Spectrum Disorder: Plausible Mechanism and Evidence.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with symptoms ranging from lack of social interaction and communication deficits to rigid, repetitive, and stereotypic behavior. It has also been associated with comorbidities such as anxiety, aggression, epilepsy, deficit in sensory processing, as well as ADHD (attention deficit hyperactivity disorder). Apart from several behavioral and cognitive complications arising as a result of central nervous system dysfunction, there are various physiological comorbidities such as immune system deregulation, neuroinflammation, oxidative stress, mitochondrial dysfunction, and gastrointestinal complications which can worsen existing behavioral complications. There are no available treatments for these physiological comorbidities. The prevalence of gastrointestinal complications in ASD ranges from 9% to 70% and it correlates with behaviors consistent with the autistic endophenotype indicating that these are one of the major comorbidities associated with ASD. A strong connection of gut-brain cross talk occurs as a result of gut dysbiosis responsible for excessive production of short-chain fatty acids such as propanoic acid (PPA) by abnormal gut flora in ASD patients. This worsens behavioral, neurochemical, and mitochondrial dysfunction occurring in ASD. These physiological comorbidities are responsible for the generation of free radical species that cause immune system dysfunction leading to synthesis of various pro-inflammatory cytokines and chemokines. This in turn causes activation of microglia. Dietary phytochemicals are thought to be safer and useful as an alternative neurotherapeutic moiety. These compounds provide neuroprotection by modulating signaling pathways such as Nrf2, NF-κB, MAPK pathway or Sirtuin-FoxO pathway. There has been recent evidence in scientific literature regarding the modulation of gut-brain cross talk responsible for behavioral, biochemical, and mitochondrial dysfunction as well as cellular and behavioral sensory alterations by dietary phytochemicals such as curcumin, resveratrol, naringenin, and sulforaphane. These dietary phytochemicals can be formulated in novel brain-targeted delivery systems which overcome their limitation of low oral bioavailability and short half-life leading to prolonged action. Till date, not much work has been done on the development of brain-targeted neurotherapeutics for ASD. In this chapter we discuss plausible mechanisms and evidence from our own and other scientific research for the utilization of curcumin, resveratrol, naringenin, and sulforaphane as neurotherapeutics for ASD.

The Gastrointestinal Exertional Heat Stroke Paradigm: Pathophysiology, Assessment, Severity, Aetiology and Nutritional Countermeasures.

Exertional heat stroke (EHS) is a life-threatening medical condition involving thermoregulatory failure and is the most severe condition along a continuum of heat-related illnesses. Current EHS policy guidance principally advocates a thermoregulatory management approach, despite growing recognition that gastrointestinal (GI) microbial translocation contributes to disease pathophysiology. Contemporary research has focused to understand the relevance of GI barrier integrity and strategies to maintain it during periods of exertional-heat stress. GI barrier integrity can be assessed non-invasively using a variety of in vivo techniques, including active inert mixed-weight molecular probe recovery tests and passive biomarkers indicative of GI structural integrity loss or microbial translocation. Strenuous exercise is strongly characterised to disrupt GI barrier integrity, and aspects of this response correlate with the corresponding magnitude of thermal strain. The aetiology of GI barrier integrity loss following exertional-heat stress is poorly understood, though may directly relate to localised hyperthermia, splanchnic hypoperfusion-mediated ischemic injury, and neuroendocrine-immune alterations. Nutritional countermeasures to maintain GI barrier integrity following exertional-heat stress provide a promising approach to mitigate EHS. The focus of this review is to evaluate: (1) the GI paradigm of exertional heat stroke; (2) techniques to assess GI barrier integrity; (3) typical GI barrier integrity responses to exertional-heat stress; (4) the aetiology of GI barrier integrity loss following exertional-heat stress; and (5) nutritional countermeasures to maintain GI barrier integrity in response to exertional-heat stress.

Gut-brain Axis and migraine headache: a comprehensive review.

The terminology "gut-brain axis "points out a bidirectional relationship between the GI system and the central nervous system (CNS). To date, several researches have shown that migraine is associated with some gastrointestinal (GI) disorders such as Helicobacter pylori (HP) infection, irritable bowel syndrome (IBS), and celiac disease (CD). The present review article aims to discuss the direct and indirect evidence suggesting relationships between migraine and the gut-brain axis. However, the mechanisms explaining how the gut and the brain may interact in patients with migraine are not entirely clear. Studies suggest that this interaction seems to be influenced by multiple factors such as inflammatory mediators (IL-1ß, IL-6, IL-8, and TNF-α), gut microbiota profile, neuropeptides and serotonin pathway, stress hormones and nutritional substances. Neuropeptides including CGRP, SP, VIP, NPY are thought to have antimicrobial impact on a variety of the gut bacterial strains and thus speculated to be involved in the bidirectional relationship between the gut and the brain. According to the current knowledge, migraine headache in patients harboring HP might be improved following the bacteria eradication. Migraineurs with long headache history and high headache frequency have a higher chance of being diagnosed with IBS. IBS and migraine share some similarities and can alter gut microflora composition and thereby may affect the gut-brain axis and inflammatory status. Migraine has been also associated with CD and the condition should be searched particularly in patients with migraine with occipital and parieto-occipital calcification at brain neuroimaging. In those patients, gluten-free diet can also be effective in reducing migraine frequency. It has also been proposed that migraine may be improved by dietary approaches with beneficial effects on gut microbiota and gut-brain axis including appropriate consumption of fiber per day, adhering to a low glycemic index diet, supplementation with vitamin D, omega-3 and probiotics as well as weight loss dietary plans for overweight and obese patients.

Clinical nutrition for the gastroenterologist: the physiologic rationale for providing early nutritional therapy to the hospitalized patient.

PURPOSE OF REVIEW: Conflicting reports in the literature have been misinterpreted by clinicians, who conclude that nutritional therapy for the hospitalized patient is of marginal value. The true benefit of such therapy is derived from the provision of early enteral nutrition. This article describes the physiologic response to enteral feeding, which accounts for the outcome benefits, and illustrates how use of the gut alters immune responses and the intestinal microbiota. RECENT FINDINGS: The provision of early enteral nutrition has been shown to reduce infection and mortality in high-risk hospitalized patients (compared with not providing such therapy). Early feeding maintains gut integrity, reduces permeability, promotes tolerance and appropriate immune responses, and supports commensalism of the intestinal microbiota. Early enteral nutrition influences cross-talk signaling between luminal bacteria and the intestinal epithelium. Failure to utilize the gut in acute illness can amplify the systemic inflammatory response syndrome and worsen disease severity, while at the same time promoting antibiotic resistance and increased septic morbidity. SUMMARY: Appropriate nutritional therapy does change outcomes in the hospitalized patient, especially for those who are at risk on the basis of disease severity and/or poor nutritional status. Greatest benefit is seen from those therapeutic regimens that specifically target gut defenses and the intestinal microbiome.

Interrogating the Gut-Brain Axis in the Context of Inflammatory Bowel Disease: A Translational Approach.

This review examines preclinical and clinical studies relevant to our understanding of how the bidirectional gut-brain axis influences the natural history of inflammatory bowel disease. Preclinical studies provide proof of concept that preexisting behavioral illness, such as depression, results in increased susceptibility to inflammatory stimuli and that commonly used classes of antidepressants protect against this vulnerability. However, clinical studies suggesting behavioral illness as a risk factor for IBD and a protective role for antidepressants have relied primarily on symptom-reporting rather than objective measurements of inflammation. In terms of gut-to-brain signaling, there is emerging evidence from preclinical and clinical observation that intestinal inflammation alters brain functions, including the induction of mood disorders, alteration of circadian rhythm both centrally and peripherally, and changes in appetitive behaviors. Furthermore, preclinical studies suggest that effective treatment of intestinal inflammation improves associated behavioral impairment. Taken together, the findings of this review encourage a holistic approach to the management of patients with IBD, accommodating lifestyle issues that include the avoidance of sleep deprivation, optimized nutrition, and the monitoring and appropriate management of behavioral disorders. The review also acknowledges the need for better-designed clinical studies evaluating the impact of behavioral disorders and their treatments on the natural history of IBD, utilizing hard end points to assess changes in the inflammatory process as opposed to reliance on symptom-based assessments. The findings of the review also encourage a better understanding of changes in brain function and circadian rhythm induced by intestinal inflammation.

Finding intestinal fortitude: Integrating the microbiome into a holistic view of depression mechanisms, treatment, and resilience.

Depression affects at least 322 million people globally, or approximately 4.4% of the world's population. While the earnestness of researchers and clinicians to understand and treat depression is not waning, the number of individuals suffering from depression continues to increase over and above the rate of global population growth. There is a sincere need for a paradigm shift. Research in the past decade is beginning to take a more holistic approach to understanding depression etiology and treatment, integrating multiple body systems into whole-body conceptualizations of this mental health affliction. Evidence supports the hypothesis that the gut microbiome, or the collective trillions of microbes inhabiting the gastrointestinal tract, is an important factor determining both the risk of development of depression and persistence of depressive symptoms. This review discusses recent advances in both rodent and human research that explore bidirectional communication between the gut microbiome and the immune, endocrine, and central nervous systems implicated in the etiology and pathophysiology of depression. Through interactions with circulating inflammatory markers and hormones, afferent and efferent neural systems, and other, more niche, pathways, the gut microbiome can affect behavior to facilitate the development of depression, exacerbate current symptoms, or contribute to treatment and resilience. While the challenge of depression may be the direst mental health crisis of our age, new discoveries in the gut microbiome, when integrated into a holistic perspective, hold great promise for the future of positive mental health.

Effectiveness and safety of light vegetarian diet on functional constipation with gastrointestinal damp-heat pattern: An exploratory study protocol for randomized controlled trial.

INTRODUCTION: Functional constipation (FC) is one of the common gastrointestinal disorders that affects people of almost every age. Persistent FC significantly affects quality of life and well-being along with economic burden on patients as well as health care system. Therapeutic efficacy of currently used treatment strategies becomes limited shortly after their discontinuation as constipation occurs again as a result of inappropriate dietary habits. Previous studies have revealed that light vegetarian diet (LVD) can significantly improve both typical and atypical subtypes of major traditional Chinese medicine (TCM) FC syndrome such as gastrointestinal damp-heat syndrome. This protocol aims at exploratorily investigating effectiveness and safety of LVD following a rigorous clinical trial. METHODS AND DESIGN: Total 92 patients in each of the 2 subtypes will be recruited in China-Japan Friendship Hospital for participating in this prospective, placebo-controlled, randomized trial and exploratory study. The patients in each subtype will be randomly divided into 4 groups according to 1:1:1:1 ratio with allocation concealment, which are drug + diet group, drug group, placebo + diet group and placebo group. Patients in the group with diet intervention will be required to strictly follow the LVD. The study will continue for a period of 28 days, including a drug or placebo supervised intervention and a 14th-day telephone follow-up. During the intervention, patients will be required to record a designed diary for controlling the diet quality (DQ) and analyzing the defecation. The study will focus investigation of complete spontaneous bowel movements (CSBM) per week as its primary outcome and constipation-related symptom rating scale (CSS), TCM syndrome scale (TCMSS), 48-hour gastrointestinal transit time (48-hour GITT), high resolution anorectal manometry (HRAM) and fecal flora detection (FFD) will be included in secondary outcomes. Furthermore, the study will also determine safety, DQ and compliance indicators. ETHICS AND DISSEMINATION: This study has been approved by China-Japan Friendship Hospital clinical research ethics committee (No. 2017-46-1). A SPIRIT checklist is available for this protocol. TRIAL REGISTRATION NUMBER: ChiCTR1800019686 in Chinese Clinical Trial Registry (WHO ICTRP member).

Factors That Worsen Disease Severity in Acute Pancreatitis: Implications for More Innovative Nutrition Therapy.

The pathophysiologic process of severe acute pancreatitis involves a vicious cycle of inflammation and increasing oxidative stress. Secretory defects trap activated pancreatic enzymes within the gland leading to autodigestion while circulatory abnormalities add the insult of ischemia/reperfusion injury. What may have the greatest impact in amplifying the systemic inflammatory response, though, is intestinal failure with breakdown of gut barrier defenses, subversion of submucosal immune responses, and emergence of a virulent pathobiome. Understanding the intricacies of these changes has broad-reaching implications for nutrition therapy, which should no longer be limited to the provision of early enteral feeding alone. Emerging strategies should attempt to maintain commensalism, bind potential pathogens, refaunate the microbiome, actively turn off inflammation, reset cross-talk signaling with epithelial receptors, and deliver nutrients further down the gastrointestinal tract to the level of greatest microbial burden. Innovative nutrition therapy for the patient with severe acute pancreatitis should be designed to address and include all of these strategies in order to shift the course of clinical outcome toward a pattern of recovery and homeostasis.

The Important Role of the Endocannabinoid System and the Endocannabinoidome in Gut Health.

The endocannabinoid system is an endogenous pathway comprised of the cannabinoid receptors 1 and 2 (CB1 and CB2), their endogenous ligands known as endocannabinoids, and the enzymes responsible for their synthesis and degradation. The endocannabinoidome extends this system to include other receptors such as TRPV1, PPARα, GPR55 and 5-HT1A. An extensive amount of research is now linking the endocannabinoidome to intestinal health through fascinating mechanisms that include endocannabinoid receptor expression in the gut and interplay with the intestinal microbiota. A dysregulated endocannabinoid system may lead to inflammatory bowel disease and colon cancer.

Gut rest strategy and trophic feeding in the acute phase of critical illness with acute gastrointestinal injury.

Critically ill patients frequently suffer from gastrointestinal dysfunction as the intestine is a vulnerable organ. In critically ill patients who require nutritional support, the current guidelines recommend the use of enteral nutrition within 24-48 h and advancing towards optimal nutritional goals over the next 48-72 h; however, this may be contraindicated in patients with acute gastrointestinal injury because overuse of the gut in the acute phase of critical illness may have an adverse effect on the prognosis. We propose that trophic feeding after 72 h, as a partial gut rest strategy, should be provided to critically ill patients during the acute phase of illness as an organ-protective strategy, especially for those with acute gastrointestinal injury.