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Parkinson’s disease (PD) is the second most common neurodegenerative disease worldwide, characterized by symptoms of bradykinesia, rigidity, postural instability, and tremor. Recently, there has been a growing focus on the relationship between the gut and the development of PD. Emerging to the forefront, an interesting concept has developed suggesting that the initial pathophysiological changes occur in the gastrointestinal tract before changes are seen within the brain. This review is aimed at highlighting the relationship between PD and the gastrointestinal tract, along with the supporting evidence for this. Firstly, we will focus on the gastrointestinal conditions and symptoms which commonly affects patients, including both upper and lower gastrointestinal issues. Secondly, the impact of nutrition and diet on neurological health and PD physiology, with particular emphasis on commonly consumed items including macronutrients and micronutrients. Finally, variability of the gut microbiome will also be discussed and its link with both the symptoms and signs of PD. The evidence presented in this review highly suggests that the initial pathogenesis in the gut may proceed the development of prodromal PD subtypes, and therefore building on this further could be imperative and lead to earlier diagnosis with new and improved therapeutics.

Gastrointestinal disturbances are one of the most common issues for endurance athletes during training and competition in the heat. The relationship between typical dietary intake or nutritional interventions and perturbations in or maintenance of gut integrity is unclear. Twelve well-trained male endurance athletes (peak oxygen consumption = 61.4 ± 7.0 ml·kg−1·min−1) completed two trials in a randomized order in 35 °C (heat) and 21 °C (thermoneutral) conditions and kept a detailed nutritional diary for eight consecutive days between the two trials. The treadmill running trials consisted of 15 min at 60% peak oxygen consumption, 15 min at 75% peak oxygen consumption, followed by 8 × 1-min high-intensity efforts. Venous blood samples were taken at the baseline, at the end of each of the three exercise stages, and 1 hr postexercise to measure gut integrity and the permeability biomarker concentration for intestinal fatty-acid-binding protein, lipopolysaccharide, and lipopolysaccharide-binding protein. The runners self-reported gut symptoms 1 hr postexercise and 3 days postexercise. The heat condition induced large (45–370%) increases in intestinal fatty-acid-binding protein, lipopolysaccharide-binding protein, and lipopolysaccharide concentrations compared with the baseline, but induced mild gastrointestinal symptoms. Carbohydrate and polyunsaturated fat intake 24 hr preexercise were associated with less lipopolysaccharide translocation. Protein, carbohydrate, total fat, and polyunsaturated fat intake (8 days) were positively associated with the percentage increase of intestinal fatty-acid-binding protein in both conditions (range of correlations, 95% confidence interval = .62–.93 [.02, .98]). Typical nutrition intake partly explained increases in biomarkers and the attenuation of symptoms induced by moderate- and high-intensity exercise under both heat and thermoneutral conditions.

Parkinson's disease (PD), the second most common neurodegenerative disease, is clinically characterized by both motor and non-motor symptoms. Although overall great achievements have been made in elucidating the etiology and pathogenesis of PD, the exact mechanisms of this complicated systemic disease are still far from being clearly understood. Consequently, most of the currently-used diagnostic tools and therapeutic options for PD are symptomatic. In this perspective review, we highlight the hot topics in recent PD research for both clinicians and researchers. Some of these hot topics, such as sleep disorders and gut symptoms, have been neglected but are currently emphasized due to their close association with PD. Following these research directions in future PD research may help understand the nature of the disease and facilitate the discovery of new strategies for the diagnosis and therapy of PD.

Supplemental digital content is available in the text., Objective Short-chain fatty acids (SCFAs) are produced by the gut microbiota and may reflect health. Gut symptoms are common in individuals with depressive disorders, and recent data indicate relationships between gut microbiota and psychiatric health. We aimed to investigate potential associations between SCFAs and self-reported depressive and gut symptoms in young adults. Methods Fecal samples from 164 individuals (125 were patients with psychiatric disorders: mean [standard deviation] age = 21.9 [2.6] years, 14% men; 39 nonpsychiatric controls: age = 28.5 [9.5] years, 38% men) were analyzed for the SCFA acetate, butyrate, and propionate by nuclear magnetic resonance spectroscopy. We then compared SCFA ratios with dimensional measures of self-reported depressive and gut symptoms. Results Depressive symptoms showed a positive association with acetate levels (ρ = 0.235, p = .003) and negative associations with both butyrate (ρ = −0.195, p = .014) and propionate levels (ρ = −0.201, p = .009) in relation to total SCFA levels. Furthermore, symptoms of diarrhea showed positive associations with acetate (ρ = 0.217, p = .010) and negative associations with propionate in relation to total SCFA levels (ρ = 0.229, p = 0–007). Cluster analysis revealed a heterogeneous pattern where shifts in SCFA ratios were observed in individuals with elevated levels of depressive symptoms, elevated levels of gut symptoms, or both. Conclusions Shifts in SCFAs are associated with both depressive symptoms and gut symptoms in young adults and may have of relevance for treatment.

INTRODUCTION: Gastric emptying scintigraphy (GES) or wireless motility capsules (WMCs) can evaluate upper gastrointestinal symptoms in suspected gastroparesis; WMC tests can also investigate lower gut symptoms. We aimed to determine whether these tests impact treatment plans and needs for additional diagnostic evaluation. METHODS: In a prospective, multicenter study, 150 patients with gastroparesis symptoms simultaneously underwent GES and WMC testing. Based on these results, investigators devised management plans to recommend changes in medications, diet, and surgical therapies and order additional diagnostic tests. RESULTS: Treatment changes were recommended more often based on the WMC vs GES results (68% vs 48%) (P < 0.0001). Ordering of additional test(s) was eliminated more often with WMC vs GES (71% vs 31%) (P < 0.0001). Prokinetics (P = 0.0007) and laxatives (P < 0.0001) were recommended more often based on the WMC vs GES results. Recommendations for prokinetics and gastroparesis diets were higher and neuromodulators lower in subjects with delayed emptying on both tests (all P ≤ 0.0006). Laxatives and additional motility tests were ordered more frequently for delayed compared with normal WMC colonic transit (P ≤ 0.02). Multiple motility tests were ordered more often on the basis of GES vs WMC findings (P ≤ 0.004). Antidumping diets and transit slowing medications were more commonly recommended for rapid WMC gastric emptying (P ≤ 0.03). DISCUSSION: WMC transit results promote medication changes and eliminate additional diagnostic testing more often than GES because of greater detection of delayed gastric emptying and profiling the entire gastrointestinal tract in patients with gastroparesis symptoms. TRANSLATIONAL IMPACT: Gastric scintigraphy and WMCs have differential impact on management decisions in suspected gastroparesis.

Nuts contain fibre, unsaturated fatty acids and polyphenols that may impact the composition of the gut microbiota and overall gut health. This study aimed to assess the impact of nuts on gut microbiota, gut function and gut symptoms via a systematic review and meta-analysis of randomised controlled trials (RCTs) in healthy adults. Eligible RCTs were identified by systematic searches of five electronic databases, hand searching of conference abstracts, clinical trials databases, back-searching reference lists and contact with key stakeholders. Eligible studies were RCTs administering tree nuts or peanuts in comparison to control, measuring any outcome related to faecal microbiota, function or symptoms. Two reviewers independently screened papers, performed data extraction and risk of bias assessment. Outcome data were synthesised as weighted mean difference (WMD) or standardised mean difference (SMD) using a random effects model. This review was registered on PROSPERO (CRD42019138169). Eight studies reporting nine RCTs were included, investigating almonds (n = 5), walnuts (n = 3) and pistachios (n = 1). Nut consumption significantly increased Clostridium (SMD: 0.40; 95% CI, 0.10, 0.71; p = 0.01), Dialister (SMD: 0.44; 95% CI, 0.13, 0.75; p = 0.005), Lachnospira (SMD: 0.33; 95% CI, 0.02, 0.64; p = 0.03) and Roseburia (SMD: 0.36; 95% CI, 0.10, 0.62; p = 0.006), and significantly decreased Parabacteroides (SMD: −0.31; 95% CI, −0.62, −0.00; p = 0.05). There was no effect of nuts on bacterial phyla, diversity or stool output. Further parallel design RCTs, powered to detect changes in faecal microbiota and incorporating functional and clinical outcomes, are needed.

Background Different dietary approaches, such as gluten and casein free diets, or the use of probiotics and prebiotics have been suggested in autistic spectrum disorders in order to reduce gastrointestinal (GI) disturbances. GI symptoms are of particular interest in this population due to prevalence and correlation with the severity of behavioural traits. Nowadays, there is lack of strong evidence about the effect of dietary interventions on these problems, particularly prebiotics. Therefore, we assessed the impact of exclusion diets and a 6-week Bimuno® galactooligosaccharide (B-GOS®) prebiotic intervention in 30 autistic children. Results The results showed that children on exclusion diets reported significantly lower scores of abdominal pain and bowel movement, as well as lower abundance of Bifidobacterium spp. and Veillonellaceae family, but higher presence of Faecalibacterium prausnitzii and Bacteroides spp. In addition, significant correlations were found between bacterial populations and faecal amino acids in this group, compared to children following an unrestricted diet. Following B-GOS® intervention, we observed improvements in anti-social behaviour, significant increase of Lachnospiraceae family, and significant changes in faecal and urine metabolites. Conclusions To our knowledge, this is the first study where the effect of exclusion diets and prebiotics has been evaluated in autism, showing potential beneficial effects. A combined dietary approach resulted in significant changes in gut microbiota composition and metabolism suggesting that multiple interventions might be more relevant for the improvement of these aspects as well as psychological traits. Trial registration NCT02720900; registered in November 2015. Electronic supplementary material The online version of this article (10.1186/s40168-018-0523-3) contains supplementary material, which is available to authorized users.

In this issue of Blood, Kakihana et al report for the first time successful and safe application of related fecal microbiota transplants (FMTs) via nasoduodenal tubes in a small series of patients suffering from steroid-resistant acute intestinal graft-versus-host disease (GVHD). In spite of concomitant cytomegalovirus and Aspergillus infections at the start of treatment, adverse effects were limited and mainly related to the mode of application. Three of 4 patients responded at the end of the observational period of 28 days after first FMT, allowing reduction of concomitant steroid dose by 69%. Four-week response was associated with restoration of commensal microbiota and accompanied by an increase of the effector regulatory T-cell/CD8 T-cell ratio in 3 of 4 patients. In the 3 responding patients, improvement of gut symptoms persisted after the last FMT, with 1 patient being alive 2 years after FMT and 2 patients finally relapsing from underlying disease 106 days and 1 year, respectively, after FMT without recurrence of GVHD.1

Gastrointestinal involvement (GI) is increasingly recognized as a major cause of both morbidity and mortality in systemic sclerosis (SSc). GI complications are common, second only to skin involvement, and affect up to 90% of patients. Although treatment modalities have changed little for upper gut symptoms such as GI reflux, there are emerging treatment modalities for the common lower gut symptoms (constipation and fecal incontinence), which will be reviewed. The important link between reflux and interstitial lung disease in SSc is also addressed. The aim of this review is to help the clinician understand and manage GI symptoms in SSc.

Heavy exercise causes gut symptoms and, in extreme cases, “heat stroke” partially due to increased intestinal permeability of luminal toxins. We examined bovine colostrum, a natural source of growth factors, as a potential moderator of such effects. Twelve volunteers completed a double-blind, placebo-controlled, crossover protocol (14 days colostrum/placebo) prior to standardized exercise. Gut permeability utilized 5 h urinary lactulose-to-rhamnose ratios. In vitro studies (T84, HT29, NCM460 human colon cell lines) examined colostrum effects on temperature-induced apoptosis (active caspase-3 and 9, Baxα, Bcl-2), heat shock protein 70 (HSP70) expression and epithelial electrical resistance. In both study arms, exercise increased blood lactate, heart rate, core temperature (mean 1.4°C rise) by similar amounts. Gut hormone profiles were similar in both arms although GLP-1 levels rose following exercise in the placebo but not the colostrum arm ( P = 0.026). Intestinal permeability in the placebo arm increased 2.5-fold following exercise (0.38 ± 0.012 baseline, to 0.92 ± 0.014, P < 0.01), whereas colostrum truncated rise by 80% (0.38 ± 0.012 baseline to 0.49 ± 0.017) following exercise. In vitro apoptosis increased by 47–65% in response to increasing temperature by 2°C. This effect was truncated by 60% if colostrum was present (all P < 0.01). Similar results were obtained examining epithelial resistance (colostrum truncated temperature-induced fall in resistance by 64%, P < 0.01). Colostrum increased HSP70 expression at both 37 and 39°C ( P < 0.001) and was truncated by addition of an EGF receptor-neutralizing antibody. Temperature-induced increase in Baxα and reduction in Bcl-2 was partially reversed by presence of colostrum. Colostrum may have value in enhancing athletic performance and preventing heat stroke.

This is the peer reviewed version of the following article: Bendezú, R. A., Barba, E., Burri, E., Cisternas, D., Accarino, A., Quiroga, S., Monclus, E., Navazo, I., Malagelada, J.-R. and Azpiroz, F. (2016), Colonic content in health and its relation to functional gut symptoms. Neurogastroenterol. Motil., 28: 849–854, which has been published in final form at [doi:10.1111/nmo.12782]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving Gut content may be determinant in the generation of digestive symptoms, particularly in patients with impaired gut function and hypersensitivity. Since the relation of intraluminal gas to symptoms is only partial, we hypothesized that non-gaseous component may play a decisive role. Methods: Abdominal computed tomography scans were evaluated in healthy subjects during fasting and after a meal (n = 15) and in patients with functional gut disorders during basal conditions (when they were feeling well) and during an episode of abdominal distension (n = 15). Colonic content and distribution were measured by an original analysis program. Key results: In healthy subjects both gaseous (87 ± 24 mL) and non-gaseous colonic content (714 ± 34 mL) were uniformly distributed along the colon. In the early postprandial period gas volume increased (by 46 ± 23 mL), but non-gaseous content did not, although a partial caudad displacement from the descending to the pelvic colon was observed. No differences in colonic content were detected between patients and healthy subjects. Symptoms were associated with discrete increments in gas volume. However, no consistent differences in non-gaseous content were detected in patients between asymptomatic periods and during episodes of abdominal distension. Conclusions & inferences: In patients with functional gut disorders, abdominal distension is not related to changes in non-gaseous colonic content. Hence, other factors, such as intestinal hypersensitivity and poor tolerance of small increases in luminal gas may be involved.

Functional gastrointestinal disorders (FGIDs) are highly prevalent and pose a significant burden on health care and society, and impact patients’ quality of life. FGIDs comprise a heterogeneous group of disorders, with unclear underlying pathophysiology. They are considered to result from the interaction of altered gut physiology and psychological factors via the gut-brain axis, where brain and gut symptoms are reciprocally influencing each other’s expression. Intestinal microbiota, as a part of the gut-brain axis, plays a central role in FGIDs. Patients with Irritable Bowel Syndrome, a prototype of FGIDs, display altered composition of the gut microbiota compared with healthy controls and benefit, at the gastrointestinal and psychological levels, from the use of probiotics and antibiotics. This review aims to recapitulate the available literature on FGIDs and microbiota-gut-brain axis.

Ingestion of food has long been linked with gut symptoms, and there is increasing interest in using diet in the management of patients with irritable bowel syndrome (IBS). The West has developed an intense interest in specialized, restrictive diets, such as those that target multiple food groups, avoid gluten, or reduce fermentable oligo-, di-, and mono-saccharides and polyols. However, most gastroenterologists are not well educated about diets or their effects on the gut. It is important to understand the various dietary approaches, their putative mechanisms, the evidence that supports their use, and the benefits or harm they might produce. The concepts behind, and delivery of, specialized diets differ from those of pharmacologic agents. High-quality research is needed to determine the efficacy of different dietary approaches and the place of specific strategies.

Gastrointestinal dysfunction is common and clinically important in patients with PD. Evidence continues to accumulate to indicate that these symptoms reflect, for the most part, the direct involvement of the gastrointestinal tract by the PD process. Gastrointestinal symptomatology may arise not only as a consequence of the effects of PD on skeletal muscles in the oropharynx, anorectum, and pelvic floor but also through the direct involvement of the autonomic and enteric nervous systems in the PD process. While many aspects of gastrointestinal dysfunction in PD continue to be delineated, therapeutic approaches to gut symptoms in this common disorder remain in their infancy. Gut involvement in PD can be seen to serve as a paradigm for gut-CNS interactions. The recent demonstration of neuropathologic abnormalities in the enteric nervous system analogous to those regarded as pathognomonic of the parkinsonian process in the CNS suggests that the enteric and central nervous systems may demonstrate parallel pathologic changes in a number of disease processes previously regarded as confined to the central and somatic nervous systems. In this way, the enteric nervous system may well serve as a more accessible "window" to a variety of degenerative neurologic disorders. With respect to PD itself, we can begin to relate both the neurologic and gastrointestinal manifestations of this disorder to defects at a number of levels (Table 1).

Regional disturbances of motility in the gastrointestinal tract have been proposed as likely pathogenetic mechanisms for a number of functional gut diseases. However, not all patients with functional gut symptoms exhibit detectable dysmotility. Some investigators have therefore postulated that visceral hypersensitivity to regional luminal stimuli underlies symptoms. The results of emerging research suggest that a pathogenic role of visceral hypersensitivity in functional gut disorders is plausible but that the issue is extremely complex, in view of the interactions between neural control of gut motility, conscious perception of gut signals, and modulation at spinal and brain centers.

Previous work in our laboratory has found that mild physical activity accelerates mouth-to-large intestinal transit of lactulose in a mixed liquid meal. Because loperamide is commonly used as an antidiarrheal agent, we wondered if it would blunt the orocecal transit acceleration provoked by mild exercise. We investigated this equation in 12 healthy persons by comparing orocolonic liquid transit at rest and in mild exercise. Each subject ingested 8 mg loperamide 1 hr prior to study under both resting and exercise conditions. With loperamide treatment, exercise (walking at 5.6 km/hr) failed to hasten increased H2 excretion (mean transit time 72 +/- 12 min at rest, 90 +/- 15 min in exercise; P = NS). This result contrasts sharply with previously reported controls: loperamide completely abolished exercise-induced orocecal transit acceleration (-23 +/- 5 min in controls; +18 +/- 13 min with loperamide; P0.05). Compared with these same controls, resting transit was not significantly slowed by the drug, while transit in exercise was retarded (64 +/- 5 min in controls, 90 +/- 15 min with loperamide; P = 0.06). Loperamide left unchanged the heart rate and oxygen uptake rises associated with exercise. In summary, by showing that loperamide blocks an exercise effect on the upper gut, these results suggest that the drug might prove effective in treating some gut symptoms induced by physical activity.

Summary. One hundred and eleven isolates of Aeromonas from water and from human sources were identified to species level and tested for the production of cytotoxin. These results were correlated with the source of each isolate and, for those from human faeces, with the clinical history of diarrhoea. A. caviae predominated in water, comprising 16 of 32 isolates; only one isolate from water was A. sobria. In human faecal samples 21 of 76 isolates were A. sobria; this was a significant difference. Cytotoxin producing strains were significantly more common in patients with no known cause for their gut symptoms. It is concluded that gastro-enteritis caused by Aeromonas is related to species and to production of cytotoxin.