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Irritable bowel syndrome (IBS) is a functional bowel disorder with 6.5% worldwide prevalence that causes gas production, abdominal distension, and abdominal pain or discomfort. This systematic review describes efficacy of the Low-Fermentable Oligosaccharides, Disaccharides, Monosaccharides And Polyols (FODMAP) diet (Low-FODMAP diet or LFD) to alleviate IBS symptoms using the PRISMA guidelines. Nine randomized controlled trials (RCT) and one non-RCT consecutive controlled study published between 2015 to 2019 were identified using PubMed and CENTRAL. Included studies involved adult IBS participants with symptoms of abdominal pain, constipation, and/or diarrhea. A total of 530 participants completed the interventions from the 10 studies included in the final systematic review with participants ranging from mean ages of 40.31±12.83 years. The LFD can be recommended to patients for its use with alleviating abdominal pain severity and quality of life; however, more research is needed to verify the efficacy of the LFD concerning stool frequency and consistency.

Background: Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder (FGID) which can be defined as chronic, relapsing visceral pain with bloating associated with change in bowel habit. It affects up to 10-15% of the adult population in the UK and is more common in females. The cost of IBS in terms of health care utilisation is substantial, exceeding £45.6 million per year in the UK alone, yet its pathophysiology is incompletely understood. Visceral pain is the main and most difficult symptom to manage in IBS and many IBS female sufferers compare it to labour pain in its severity. Modulating visceral pain in healthy volunteers and IBS patients is therefore an important research area. Non-invasive magnetic stimulation may play a crucial role in this respect. Aim:The aim of this study is to ascertain whether non-invasive repetitive magnetic stimulation applied to the motor cortex and/or lumbosacrum can modulate gastrointestinal pain originating from the anorectum. Methods:Participants: 16 healthy volunteers and 10 IBS patients aged 18 and above were included in the study.Questionnaires: Healthy volunteers and IBS patients were asked to complete anxiety and depression questionnaire and IBS patients were requested to fill in an IBS severity questionnaire.Motor measurements in healthy subjects: Single-pulse lumbosacral magnetic stimulation (LSMS) was applied to the lumbosacral area for the anal sphincter where the largest motor evoked potential (MEP) amplitude response was detected. Single-pulse transcranial magnetic stimulation (TMS) was then performed at the pre-determined resting motor thresholds (RMT) for the anal sphincter and the hand.Sensory measurements in healthy subjects and IBS patients: Electrical stimulation was used to assess the changes in sensory and pain thresholds in the anorectal area. The subjects were asked to score the pain intensity using five-point categorical rating scales. In addition they were asked to describe the pain experienced using a shortened form of the McGill Pain Questionnaire. Intervention: Healthy volunteers received 6 paradigms of magnetic stimulation in a randomised order i.e. 3 repetitive LSMSs (1 Hz, 10 Hz and sham) and 3 repetitive TMSs (1 Hz, 10 Hz and sham) to investigate their modulatory effects on visceral sensitivity and to determine which of these interventions is most effective. The most effective active interventions (1 Hz rLSMS and 10 Hz rTMS) together with one sham were then trialled in a randomised fashion on IBS patients.Post intervention: Motor excitabilities were repeated at 30 min after each intervention. The assessment of sensory and pain thresholds at anal sphincter and rectum were done immediately, 30 and 60 min after each intervention. Results:Application of 1 Hz rLSMS led to alterations of anal sphincter motor excitabilities and resulted in a significant increase in the amplitude of lumbosacal-anal motor evoked potentials (MEPs) in healthy volunteers recorded at 30 min post intervention. In healthy volunteers, 1 Hz rLSMS and 10 Hz rTMS caused a significant increase in the rectal pain thresholds experienced immediately, 30 and 60 min after each intervention. 10 Hz rLSMS and 1 Hz rTMS only led to a significant rise in rectal pain thresholds immediately after their application. Furthermore, there was a significant increase in the rectal pain thresholds immediately, 30 and 60 min following 1 Hz rLSMS and 10 Hz rTMS in IBS patients. Conclusion:The application of magnetic stimulation to the cortical and lumbosacral areas to modulate visceral pain is a new concept, which reduced rectal sensitivity to painful stimuli and offers a much needed new approach in the management of abdominal pain in patients with IBS.

The herbal preparation coffee charcoal is produced by over-roasting and milling green dried Coffea arabica L. seeds, and has a long-standing tradition in the treatment of inflammatory and gastrointestinal disorders. Its therapeutic properties are commonly attributed to adsorptive and astringent effects. This insufficiently explains its mode of action, especially when used in the treatment of inflammatory diseases in lower dosages. Our investigations aimed to identify bioactive secondary plant metabolites affecting cytokine-signaling. Thus, a phytochemical analysis of coffee charcoal extract was conducted using HPLC and LC/MS. Trigonelline, neochlorogenic acid, chlorogenic acid, caffeine, cryptochlorogenic acid, feruloylquinic acid isomers, and a caffeoylquinolacton were identified in the extract. Subsequently, the effects of coffee charcoal extract, chlorogenic acid isomers, their metabolite caffeic acid, caffeine, and trigonelline on cytokine (TNF, IL-6, MCP-1) release from LPS-challenged human THP-1 macrophages were examined to evaluate anti-inflammatory activity. Coffee charcoal showed concentration-dependent mild-to-medium inhibitory effects. The chlorogenic acid isomers and caffeic acid inhibited the TNF release, with cryptochlorogenic acid exerting the most distinct effects, as well as decreasing the release of IL-6 and MCP-1. In addition, scanning electron microscopic images provided an impression of the particle constitution, indicating a larger particle size and less structured surface of coffee charcoal in comparison to activated charcoal. In conclusion, our findings underline that beyond adsorptive effects, coffee charcoal exhibits pharmacological properties, which derive from a spectrum of secondary plant metabolites and support the therapeutic use in inflammatory diseases. Chlorogenic acids, particularly cryptochlorogenic acid, appear as pivotal bioactive compounds.

A diabetes mellitus (DM) pode levar a distúrbios da motilidade gastrointestinal que podem se tornar clinicamente relevantes em alguns pacientes. Modelos de Dm em roedores indicam anormalidades morfofuncionais do sistema nervoso entérico nessa doença. Neste trabalho, avaliamos se o DM experimental pode levar a alterações na eferência colinérgica excitatória, densidade neuronal e expressão dos canais de sódio voltagemdependente (Nav) no plexo mioentérico do íleo. Hiperglicemia induzida por estreptozotocina em ratas foi desenvolvida durante oito semanas. Experimentos de imunofluorescência de tripla marcação revelaram que a densidade de neurônios por área do íleo no DM foi significativamente reduzida quando comparada ao controle. Foram observadas reduções médias de 52,2% do total de neurônios (p=0,0001); 50,0% dos neurônios colinérgicos (p=0,0068) e 54,8% dos neurônios nitrérgicos (p=0,0042). Também foram observadas reduções significativas de neurônios por área de gânglio (28,2% do total, p=0,0002; 27,7% de colinérgicos, p= 0,0002 e 32,1% de neurônios nitrérgicos, p=0,0016). A densidade de fibras colinérgicas na superfície do músculo longitudinal também foi significativamente reduzida (controle: 41 ± 2, DM: 24 ± 3%; p=0,003), embora a análise western-blot não indicasse redução na expressão de ChAT no DM. grupo. A isoforma Nav1.6 foi detectada em diferentes neurônios mioentéricos e a DM tendeu a mudar o padrão de imunomarcação para neurônios de tamanho maior (297,4 ± 10 vs. 372,5 ± 8,4 µm2), mas esse efeito não foi significativo (p=0,3). Os dados de RT-qPCR não sugeriram uma alteração dos transcritos para ChAT, nNOS, Nav1.3, Nav1.6 ou Nav1.7. Nossos dados confirmam a visão de que o DM crônico leva à redução das fibras colinérgicas excitatórias e da densidade neuronal. No entanto, mudanças no perfil de expressão do canal de sódio, que poderiam levar à disfunção neuronal, não foram detectadas. / Diabetes mellitus (DM) may lead to gastrointestinal motility disorders that may become clinically relevant in some patients. Rodent models of DM indicate morpho-functional abnormalities of the enteric nervous system in this disease. In this work, we have evaluated whether experimental DM can lead to changes in excitatory cholinergic efference, neuronal density and voltage-gate sodium channels (Nav) expression in the myenteric plexus of ileum. Streptozotocin-induced hiperglycemia in female rats was allowed to develop during eight weeks. Triple immunofluorescence labeling experiments revealed that the density of neurons per area of ileum in DM was significantly reduced when compared to the control. It were observed average reductions of 52.2% of total neurons (p=0.0001); 50.0% of cholinergic (p=0.0068) and 54.8% of nitrergic neurons (p=0.0042). Significant reductions of neurons per area of ganglion were also observed (28.2% of total, p=0.0002; 27.7% of cholinergic, p=0,0002 and 32.1% of nitrergic neurons, p=0.0016). The cholinergic fibers density at the surface of longitudinal muscle was also significantly reduced (control: 41 ± 2, DM: 24 ± 3%; p=0.003), although western-blot analysis did not indicate a reduction in the expression of ChAT in DM group. The Nav1.6 isoform was detected in different myenteric neurons and DM tended to shift the immunolabeling pattern towards neurons of bigger size (297.4 ± 10 vs. 372.5 ± 8.4 m2), but this effect was not significant (p=0.3). RT-qPCR data did not suggest an alteration of transcripts for ChAT, nNOS, Nav1.3, Nav1.6 or Nav1.7. Our data support the view that chronic DM leads to reduction in excitatory cholinergic fibers and neuronal density. However, changes in sodium channel expression profiling, which could lead to neuronal dysfunction, were not detected. / Fundação de Amparo à Pesquisa do Estado de Minas Gerais

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