Edible seaweeds have been consumed by Asian coastal communities since ancient times. Fucus vesiculosus and Ascophyllum nodosum extracts have been traditionally used for the treatment of obesity and several gastrointestinal diseases. We evaluated the ability of extracts obtained from these algae to inhibit the digestive enzymes α-amylase and α-glucosidase in vitro, and control postprandial plasma glucose levels in a mouse model of non-alcoholic steatohepatitis (NASH); a liver disease often preceding the development of Type 2 diabetes (T2DM). This model was obtained by the administration of a high-fat diet. Our results demonstrate that these algae only delayed and reduced the peak of blood glucose (p < 0.05) in mice fed with normal diet, without changing the area under the blood glucose curve (AUC). In the model of NASH, the phytocomplex was able to reduce both the postprandial glycaemic peak, and the AUC. The administration of the extract in a diet particularly rich in fat is associated with a delay in carbohydrate digestion, but also with a decrease in its assimilation. In conclusion, our results indicate that this algal extract may be useful in the control of carbohydrate digestion and absorption. This effect may be therapeutically exploited to prevent the transition of NASH to T2DM.

Objective: Toll-like receptors (TLRs) play a pivotal role in the homeostatic microflora-host crosstalk. TLR4-mediated modulation of both motility and enteric neuronal survival has been reported mainly for colon with limited information on the role of TLR4 in tuning structural and functional integrity of enteric nervous system (ENS) and in controlling small bowel motility. Methods: Male TLR4 knockout (TLR4^-/-, 9 ± 1 weeks old) and sex- and age-matched wild-type (WT) C57BL/6J mice were used for the experiments. Alterations in ENS morphology and neurochemical code were assessed by immunohistochemistry whereas neuromuscular function was evaluated by isometric mechanical activity of ileal preparations following receptor and non-receptor-mediated stimuli and by gastrointestinal transit. Results: The absence of TLR4 induced gliosis and reduced the total number of neurons, mainly nNOS⁺ neurons, in ileal myenteric plexus. Furthermore, a lower cholinergic excitatory response with an increased inhibitory neurotransmission was found together with a delayed gastrointestinal transit. These changes were dependent on increased ileal non-adrenergic non-cholinergic (NANC) relaxations mediated by a complex neuronal-glia signaling constituted by P2X7 and P2Y1 receptors, and NO produced by nNOS and iNOS. Conclusion: We provide novel evidence that TLR4 signaling is involved in the fine-tuning of P2 receptors controlling ileal contractility, ENS cell distribution, and inhibitory NANC neurotransmission via the combined action of NO and adenosine-5′-triphosphate (ATP). For the first time, this study implicates TLR4 at regulating the crosstalk between glia and neurons in small intestine and helps to define its role in gastrointestinal motor abnormalities during dysbiosis.

The treatment for coeliac disease (CD) has a considerable psychological impact on patients, which may vary depending on subjects and clinical characteristics. The aim of this study was to describe the quality of life (QoL) in CD patients during follow-up, evaluating which factors can influence it. Patients with CD who consecutively visited the outpatient clinic of CD Unit of the University Hospital of Padua from January to September 2019 were enrolled. Demographics and clinical information were collected, and all patients were asked to answer the CD-QoL and Biagi’s validated questionnaires. Student’s t-test and chi-square test were used to compare the continuous and categorical variables, respectively. One hundred patients were enrolled (86 females, mean age at test ± SD: 39.73 ± 13.51; mean age at diagnosis ± SD: 33.09 ± 12.92), with 61% of them having been diagnosed with CD within the previous 5 years. At the time of diagnosis, 43 CD patients reported classical CD presentation, 32 non-classical features, 16 only anaemia and 9 were asymptomatic. The mean CD-QoL value was overall high (80.54 ± 11.91). We found that the “health concerns” subscale score was significantly lower in subjects aged more than 35 years compared to younger subjects (p = 0.03). We also observed that the CD-QoL score in gluten-free diet (GFD)-adherent patients tended to be higher compared to subjects who were non-compliant, with a significantly higher percentage of patients with low score for the “dysphoria” subscale (p = 0.05). This study showed an overall good QoL in subjects on a GFD. However, subjects older and non-compliant to GFD appear to experience more health concerns and suffer from dysphoria, respectively.

Coeliac disease (CeD) has been associated with psychological disorders and reduced quality of life. Our prospective study evaluated the changes in the quality of life, anxiety and depression in CeD patients up to two years after diagnosis. We recruited adult patients residing in the Veneto region with a new diagnosis of CeD. Several validated questionnaires were administered to measure quality of life, psychological symptoms and adherence to a gluten-free diet (GFD) at the time of diagnosis and after 1 and 2 years. Ninety-three patients reached the 1-year follow-up (81.7% were females with a median age at diagnosis of 35 years), and 55 patients reached the 2-year follow-up. We observed a significant improvement in quality of life, anxiety and depression scores at 1 year after diagnosis, particularly in patients who complied with a GFD. The improvements among classical CeD patients were similar to those observed in nonclassical patients except for anxiety, which improved only in patients with a classical presentation at diagnosis. Age, sex and other disease factors did not affect the change in quality of life (QoL) or other mood disorders. Most of the improvements measured 1 year after diagnosis and 2 years after diagnosis were not significant. In conclusion, QoL and mood disorders must be considered, and psychological counselling should be used when needed.

Enteric glial cells (EGCs) influence nitric oxide (NO)⁻ and adenosine diphosphate (ADP)⁻ mediated signaling in the enteric nervous system (ENS). Since Toll-like receptor 4 (TLR4) participates to EGC homoeostasis, this study aimed to evaluate the possible involvement of EGCs in the alterations of the inhibitory neurotransmission in TLR4^−/− mice. Ileal segments from male TLR4^−/− and wild-type (WT) C57BL/6J mice were incubated with the gliotoxin fluoroacetate (FA). Alterations in ENS morphology and neurochemical coding were investigated by immunohistochemistry whereas neuromuscular responses were determined by recording non-adrenergic non-cholinergic (NANC) relaxations in isometrically suspended isolated ileal preparations. TLR4^−/− ileal segments showed increased iNOS immunoreactivity associated with enhanced NANC relaxation, mediated by iNOS-derived NO and sensitive to P2Y1 inhibition. Treatment with FA diminished iNOS immunoreactivity and partially abolished NO⁻ and ADP⁻ mediated relaxation in the TLR4^−/− mouse ileum, with no changes of P2Y1 and connexin-43 immunofluorescence distribution in the ENS. After FA treatment, S100β and GFAP immunoreactivity in TLR4^−/− myenteric plexus was reduced to levels comparable to those observed in WT. Our findings show the involvement of EGCs in the alterations of ENS architecture and in the increased purinergic and nitrergic-mediated relaxation, determining gut dysmotility in TLR4^−/− mice.