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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.

Gastroparesis presents with nausea, vomiting, and other upper gut symptoms, and is diagnosed by confirming delayed gastric emptying. A related condition, chronic unexplained nausea and vomiting, has similar symptoms but with normal emptying. Both conditions are managed using therapies with diverse mechanisms of action. Even though prokinetic treatments are proposed to improve gastroparesis by accelerating gastric emptying, there is limited evidence that they provide benefit by virtue of transit stimulating effects. Other tests can delineate alterations in other gut sensorimotor parameters in patients with suspected gastroparesis, but their relation to symptoms and their capability to guide treatment are largely unproved.

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.

Functional upper gut symptoms and functional dyspepsia represent frequent conditions in clinical practice. As objectively measurable physiological and structural abnormalities...

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.

Introduction The low FODMAP diet is known to be effective in improving symptoms in approx. 70% of those with Rome criteria IBS. Whilst the majority of IBS patients are young adults, there is a cohort of patients over the age of 45 with IBS who may benefit from similar interventions. In January 2017, the dietetic-led refractory IBS (RIBS) Service in Gloucestershire expanded its direct access inclusion criteria to allow GP referral of patients >45 years with negative GI investigation within the previous 5 years and no change in symptoms. Consultant referrals following negative investigation in this age group are also accepted. Methods This is a retrospective analysis of data collected during patient consultations. Patients over 45 years referred to the RIBS service by GP or consultant were assessed and provided with detailed advice on a low FODMAP diet by a specialist dietitian, to be followed for 6 weeks. An 11 point symptom evaluation was completed before and after dietary manipulation and total scores were calculated. Typical bowel frequency and stool consistency were recorded, along with responses to a global symptom question ‘do you currently have satisfactory relief of your gut symptoms?’ Results 107 patients>45 years of age have completed treatment within the RIBS service (82% with diarrhoea or mixed symptom predominance). Individual and total symptom scores demonstrate an average reduction in severity of almost 50% after following a FODMAP exclusion diet (figure 1), with mean total symptom score before treatment 60.9 (range 27–89/110) reducing to 36.0 after treatment (range 11–89/110). Sixty-seven percent (72/107) of patients reported satisfactory relief of their gut symptoms following dietary restriction (figure 2). Direct-access patients who did not respond to treatment were discussed within a consultant-led MDT, with further advice, clinician review or investigation arranged as appropriate. No known cases of IBD or cancer have been missed to date using this pathway of care. Conclusions Treatment within a dietetic-led, direct-access service with an appropriate, policed care pathway and MDT support is a safe and clinically effective management strategy for patients over the age of 45 with diagnosed IBS symptoms. The pathway provides an important adjunct to ‘straight to test’ referral protocols for GP’s in those over 45 with stable symptoms and previously negative colonoscopy, diverting these patients from unnecessary specialist review and costly further investigation.

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.

Lactose intolerance is a very common complaint which leads to a number of distressing gut symptoms in those affected. It can be quite easy to control by reducing milk consumption, and possibly by adding lactase to the diet. However, clinicians should be wary of over-diagnosing this condition, particularly in the indigenous white population, and thereby depriving the individual of a useful, cheap and nutritious food. If lactose intolerance is suspected, it should be carefully investigated and diagnosed, prior to the introduction of dietary management.

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.

Background: Several governmental efforts have been exerted toward controlling schistosomiasis during the last decades in Egypt. This work was designed to study the prevalence of colorectal schistosomiasis in patients with different gastrointestinal symptoms. Materials and Methods: Patients presented to the gastroenterology unit with different gastrointestinal symptoms were endoscopically examined, where three to six tiny biopsies were taken from those with visible, suspected schistosomal lesions for histopathological examination and two additional rectal biopsies were taken from the apparently normal colonic mucosa. Form each patient, at least three stool samples were examined by the formal-ether concentration method for schistosoma ova. Results: Colonic abnormalities were detected in 510 out of 984 patients presented with different gut symptoms. Schistosoma mansoni was detected in 205 patients (180 males, 25 females) with an age range (18-65years). Six patients only had schistosomal polyps and excised successfully by snare polypectomy. The squash technique established the diagnosis of schistosomiasis in all endoscopically normal 118 (50.75%) cases by demonstrating the schistosomiasis ova and their associated histopathological findings showed no or minimal reaction in 96 (46.82%) cases and variable degrees of submucosal granulomata in the remaining cases. Stool examination detected the schistosomiasis ova in 25 (9.83%) patients only of the biopsy-positive cases. Conclusions: Our data revealed that despite governmental efforts, the prevalence of colorectal schistosomiasis (20.83%) is significant among patients with gut symptoms. Gaps in health care services should be detected and filled appropriately.

Abdominal symptoms due to motility disturbances of the lower gut consist mainly of discrete pain episodes or a long-lasting feeling of fullness and distension. Long-term recording has shown that these symptoms are partly related to propagated contraction waves of the colon which induce mass movement of colonic contents. Patients probably experience that normal contractile activity is unpleasant or painful and apparently have a decreased threshold of perception. Also, peculiar contraction patterns of the small intestine ('clustered contractions') have been related to pain episodes. Fullness and distension are characteristic for slow transit constipation, but also occur in disordered defecation. Future studies on treatment will have to concentrate on pathophysiologically defined subgroups.

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.

Background: High Resolutions Manometry (HRM) is the gold standard for the categorisation of motility disorders of the oesophagus, with achalasia as one of the most distinct manometric conditions. We aimed to compare the gastrointestinal symptom pattern and intensity in patients referred for HRM with and without a final diagnosis of achalasia utilising the recently developed SAGIS (Structured Assessment of Gastrointestinal Symptoms) instrument. Methods: Data from 50 consecutive patients referred for HRM for dysphagia were included in this study, mean age 56 years, range 17-84, 28 female. All patients had a negative upper GI endoscopy and other tests required to exclude structural abnormalities. Gastrointestinal symptoms were assessed prior to the HRM utilising the SAGIS questionnaire. Results: Based upon the Chicago Classification, 9 out of the 50 patients were diagnosed as having achalasia (6 males, 3 females). Overall, neither dysphagia nor the cumulated upper GI symptom score or scores for retrosternal discomfort were different for patients with or without achalasia (table 1). In contrast, patients with non-specific motor abnormalities had increased scores for IBS-type lower gut symptoms. Conclusions: Utilising the recently developed SAGIS instrument, patients with achalasia are not different from dysphagia patients with no/unspecific motor abnormalities of the oesophagus with regard to upper gastrointestinal symptoms. In particular, there are no differences in relation to the dysphagia or the retrosternal discomfort score. In contrast, patients with no/unspecific motor abnormalities, scored much higher for lower gastrointestinal symptoms than achalasia patients. In addition, IBS-type symptoms such as urgency to defecate are significantly increased. In patients with dysphagia, the presence of lower gut symptoms is a negative predictor for achalasia. Table 1

Introduction The low FODMAP diet is an effective intervention for people with functional bowel disorders (FBD). It has been introduced successfully to the UK with > 250 dietitians trained in its implementation. However, teaching patients about the diet is labour intensive; initial appointments typically last one hour. Given the prevalence of FBD, this represents a significant obstacle to widespread use. Group education sessions (GS) are a possible solution and are effective for dietary interventions in other disorders (e.g. diabetes, obesity), although their effectiveness has not been established for the low FODMAP diet. We aimed to compare the effectiveness of GS with one-to-one sessions (OS). Methods Patients referred in 2011–12 with FBD were pre-assessed by telephone to confirm suitability for GS. Those with atypical symptoms or with other medical or nutritional concerns were excluded. Suitable patients were offered the choice of GS or OS. Up to 12 patients were seen in each GS lasting 1.5h and were then followed up 6–10 weeks later in a 1h GS. Patients seen in OS had an initial 1h appointment and then a 0.33h follow-up, 6–10 weeks later. Effectiveness of the diet was compared in OS and GS. Symptoms were measured using the gastrointestinal symptom rating scale at baseline and follow-up and clinical effectiveness through the global symptom question (GSQ). Comparisons were made using the χ2 test. Acceptability of GS sessions was also assessed. Results Data from 168 patients attending GS (70% female, mean age 39y) were compared with 50 patients attending OS (60% female, mean age 47y). Positive responses to the GSQ ‘do you currently have satisfactory relief of your gut symptoms’ improved from 30/155 (19%) at baseline to 71/146 (49%) in the GS (P 50% of the time. Most of the GS patients felt length of the sessions (95%), content (93%) and balance between education and patient involvement (95%) were ‘just right’. In retrospect, 39% would have preferred OS, with the remainder preferring GS or expressing no preference. Conclusion GS are an effective medium for instructing patients in the implementation of the low FODMAP diet. Whilst a significant minority attending GS would have preferred OS, there are several possible advantages to GS including peer-support and sharing of experiences. Most importantly, GS allow increased capacity and shorter waiting times. Disclosure of Interest None Declared.

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).

TO THE EDITOR: We thank Dr. Mann for his interest in our article (1). Dr. Mann focuses in his letter on possible explanations for the overlap of upper gastrointestinal tract symptoms in irritable bowel syndrome (IBS) with constipation. However, we were also struck in this study by the overlap of IBS with diarrhea and upper gut symptoms, although the symptom patterns were somewhat different. Another potential explanation for the overlap of both bowel habit subtypes of IBS with functional dyspepsia is that these processes represent a continuum with a similar underlying etiopathogenesis; the differing manifestations may depend on both genetics and environment (2).

Functional upper gut symptoms, such as nausea, vomiting and abdominal pain, are a continuing challenge in gastroenterological practice. This article considers the approaches applied in recent years to evaluate motor function in the upper gut including manometry and radio-nuclide transit studies, and symptom-provocation tests such as balloon distension and pharmacologic stimulation. An approach is proposed that is based on positive symptomatic diagnosis of the disturbed pathophysiologic state, followed by treatment of this disturbance of function after a minimum of confirmatory investigations.

There is a tendency to deprecate functional complaints. Physicians are trained to get to the organic core of a problem and to understand disease in terms of its pathology. When there is no structural or biochemical abnormality, symptoms are difficult to understand. It is easiest to ignore or dismiss that which is not understood. Thus the aim in diagnosis is to identify or exclude pathology. The irritable gut is what is left when no organic explanation for gut symptoms can be found. This negative approach to the diagnosis of functional disease leads to tests and therapy that may be inappropriate and often trivialize patients’ complaints (Figure 10). After all, no one has ever died from an irritable gut.

In children with AD an abnormal absorption of macromolecules (mac) through the gut was observed. We challenged 6 children (11 mths. to 11 yrs. of age) affected by AD with in vivo and in vitro evidence of hypersensitivity to ovoalbumin (OA) and 4 to cow's milk (α-lactalbumin AL) . The children were challenged with the specific allergenic food, the challenge was repeated with the pretreatment of oral SCG (40 mg/kg). The detection of mac. (OA, AL) in circulation was performed in solid phase (Paganelli et al.). Results: 1) All the patients had skin and gut symptoms on the 1st occasion. Pretreatment with SCG prevented the occorrence of immediate symptoms; 2) Circulating Ag detected in sera after specific food challenge: SCG was able to reduce the absorption of mac. This finding may indicate that effectiveness of SCG in preventing the symptoms is due to both reduced and delayed absorption.