Associations between various markers of intestinal barrier and immune function after a high-intensity exercise challenge.

Strenuous exercise can result in disruption of intestinal barrier function and occurrence of gastrointestinal symptoms. The aim of this exploratory study was to elucidate systemic effects of increased intestinal permeability after high-intensity exercise. Forty-one endurance-trained subjects performed a 60-min treadmill run at 80% VO2max. Small intestinal permeability was measured as urinary excretion ratio of lactulose/rhamnose (L/R). Blood, saliva and feces were analyzed for gut barrier and immune-related biomarkers. The exercise challenge increased several markers of intestinal barrier disruption, immune function and oxidative stress. We found a negative correlation between L/R ratio and uric acid (r = -0.480), as well as a positive correlation between the L/R ratio and fecal chromogranin A in male participants (r = 0.555). No significant correlations were found between any of the markers and gastrointestinal symptoms, however, perceived exertion correlated with the combination of IL-6, IL-10 and salivary cortisol (r = 0.492). The lack of correlation between intestinal permeability and gastrointestinal symptoms could be due to minor symptoms experienced in lab settings compared to real-life competitions. The correlation between L/R ratio and uric acid might imply a barrier-protective effect of uric acid, and inflammatory processes due to strenuous exercise seem to play an important role regarding physical exhaustion.

Hospital-treated infections and subsequent Parkinson's disease risk: a register-based sibling comparison study.

Serious infections may result in greater risk of Parkinson's disease. However, high-quality cohort studies focusing on a potential causal role of different types and sites of infection are lacking. Gastrointestinal infections are of a particular interest due to growing evidence implicating gut dysbiosis in Parkinson's disease aetiology. This population-based cohort study used the Swedish Total Population Register to identify individuals born during 1944-77 and resident in Sweden between 1990 and 2018 (N = 3 698 319). Hospital-treated infections at ages 21-30 and 31-40 years were identified from the National Patient Register. Participants were followed to identify Parkinson's disease diagnoses from age 41 years up to December 31, 2018, when the oldest individual reached 75 years. Cox regression with a sibling comparison design to tackle familial genetic and environmental confounding was used to derive hazard ratios and 95% confidence intervals for each infection site, type, or any infections at ages 21-30 and 31-40 years. During a median follow-up of 15.4 years, 8815 unique Parkinson's disease diagnoses were accrued, with a crude rate of 17.3 (95% confidence interval 17.0, 17.7) per 100 000 person-years. After controlling for shared familial factors, hospital-treated gastrointestinal and respiratory infections between 21 and 30 years of age were associated with a greater risk of Parkinson's disease [hazard ratios 1.35 (95% confidence interval: 1.05, 1.75) and 1.45 (95% confidence interval: 1.08, 1.95), respectively]; no association was found for any infections at age 31-40 [hazard ratio 1.05 (95% confidence interval: 0.93, 1.19)]. After adjustment, no statistically significant associations were observed for other sites including genitourinary and skin. These findings suggest that hospital-treated infections of the gastrointestinal tract and lungs, both of which may have an influence on the gut microbiome, by age 30 years may be risk factors for Parkinson's disease.

Limosilactobacillus reuteri DSM 17938 supplementation and SARS-CoV-2 specific antibody response in healthy adults: a randomized, triple-blinded, placebo-controlled trial.

Studies have shown that probiotics can decrease the symptoms of respiratory tract infections as well as increase antibody responses following certain vaccinations. We examined the effect of probiotic supplementation on anti-SARS-CoV-2 specific antibody responses upon SARS-CoV-2 infection as well as after COVID-19 vaccination. In this randomized, triple-blinded, placebo-controlled intervention study with a parallel design, 159 healthy adults without prior SARS-CoV-2 infection or COVID-19 vaccination and any known risk factors for severe COVID-19 were randomly allocated into two study arms. The active treatment arm consumed a probiotic product containing a minimum of 1 × 108 colony-forming units of Limosilactobacillus reuteri DSM 17938 + 10 µg vitamin D3 twice daily for 6 months. The placebo arm consumed identical tablets containing only 10 µg vitamin D3. Anti-SARS-CoV-2 specific antibodies and virus neutralizing antibody titers were analyzed from blood samples collected at baseline, after 3 months, and after 6 months. Differences in serum antibody titers between the two study arms were tested with independent t-test using log-transformed values. In the intention-to-treat (ITT) analysis, SARS-CoV-2 infected individuals in the active treatment arm (n = 6) tended to have higher serum anti-spike IgG (609 [168-1480] BAU/ml vs 111 [36.1-1210] BAU/ml, p = 0.080) and anti-receptor binding domain (RBD) IgG (928 [212-3449] BAU/ml vs (83.7 [22.8-2094] BAU/ml, p = 0.066) levels than individuals in the placebo arm (n = 6). Considering individuals who were fully vaccinated with mRNA-based COVID-19 vaccines, the active treatment arm (n = 10) exhibited significantly higher serum levels of anti-RBD IgA (135 [32.9-976] BAU/ml vs 61.3 [26.7-97.1] BAU/ml, p = 0.036) than the placebo arm (n = 7) >28 days postvaccination. Supplementation with specific probiotics might improve the long-term efficacy of mRNA-based COVID-19 vaccines via enhanced IgA response.

Potential Modulation of Inflammation and Physical Function by Combined Probiotics, Omega-3 Supplementation and Vitamin D Supplementation in Overweight/Obese Patients with Chronic Low-Grade Inflammation: A Randomized, Placebo-Controlled Trial.

Obesity is characterized by low-grade inflammation and increased gut permeability. Here, we aim to evaluate the effect of a nutritional supplement on these parameters in subjects with overweight and obesity. A double-blinded, randomized clinical trial was conducted in 76 adults with overweight or obesity (BMI 28 to 40) and low-grade inflammation (high-sensitivity C-reactive protein (hs-CRP) between 2 and 10 mg/L). The intervention consisted of a daily intake of a multi-strain probiotic of Lactobacillus and Bifidobacterium, 640 mg of omega-3 fatty acids (n-3 FAs), and 200 IU of vitamin D (n = 37) or placebo (n = 39), administered for 8 weeks. hs-CRP levels did not change post-intervention, other than an unexpected slight increase observed in the treatment group. Interleukin (IL)-6 levels decreased in the treatment group (p = 0.018). The plasma fatty acid (FA) levels of the arachidonic acid (AA)/eicosapentaenoic acid (EPA) ratio and n-6/n-3 ratio (p < 0.001) decreased, and physical function and mobility improved in the treatment group (p = 0.006). The results suggest that hs-CRP may not be the most useful inflammatory marker, but probiotics, n-3 FAs, and vitamin D, as non-pharmaceutical supplements, may exert modest effects on inflammation, plasma FA levels, and physical function in patients with overweight and obesity and associated low-grade inflammation.

Potential Modulation of Inflammation by Probiotic and Omega-3 Supplementation in Elderly with Chronic Low-Grade Inflammation-A Randomized, Placebo-Controlled Trial.

Probiotic and omega-3 supplements have been shown to reduce inflammation, and dual supplementation may have synergistic health effects. We investigated if the novel combination of a multi-strain probiotic (containing B. lactis Bi-07, L. paracasei Lpc-37, L. acidophilus NCFM, and B. lactis Bl-04) alongside omega-3 supplements reduces low-grade inflammation as measured by high-sensitivity C-reactive protein (hs-CRP) in elderly participants in a proof-of-concept, randomized, placebo-controlled, parallel study (NCT04126330). In this case, 76 community-dwelling elderly participants (median: 71.0 years; IQR: 68.0-73.8) underwent an intervention with the dual supplement (n = 37) or placebo (n = 39) for eight weeks. In addition to hs-CRP, cytokine levels and intestinal permeability were also assessed at baseline and after the eight-week intervention. No significant difference was seen for hs-CRP between the dual supplement group and placebo. However, interestingly, supplementation did result in significant increases in the level of the anti-inflammatory marker IL-10. In addition, dual supplementation increased levels of valeric acid, further suggesting the potential of the supplements in reducing inflammation and conferring health benefits. Together, the results suggest that probiotic and omega-3 dual supplementation exerts modest effects on inflammation and may have potential use as a non-pharmacological treatment for low-grade inflammation in the elderly.

Multi-Strain Probiotic Mixture Affects Brain Morphology and Resting State Brain Function in Healthy Subjects: An RCT.

Probiotics can alter brain function via the gut-brain axis. We investigated the effect of a probiotic mixture containing Bifidobacterium longum, Lactobacillus helveticus and Lactiplantibacillus plantarum. In a randomized, placebo-controlled, double-blinded crossover design, 22 healthy subjects (6 m/16 f; 24.2 ± 3.4 years) underwent four-week intervention periods with probiotics and placebo, separated by a four-week washout period. Voxel-based morphometry indicated that the probiotic intervention affected the gray matter volume of a cluster covering the left supramarginal gyrus and superior parietal lobule (p < 0.0001), two regions that were also among those with an altered resting state functional connectivity. Probiotic intervention resulted in significant (FDR < 0.05) functional connectivity changes between regions within the default mode, salience, frontoparietal as well as the language network and several regions located outside these networks. Psychological symptoms trended towards improvement after probiotic intervention, i.e., the total score of the Hospital Anxiety and Depression Scale (p = 0.056) and its depression sub-score (p = 0.093), as well as sleep patterns (p = 0.058). The probiotic intervention evoked distinct changes in brain morphology and resting state brain function alongside slight improvements of psycho(bio)logical markers of the gut-brain axis. The combination of those parameters may provide new insights into the modes of action by which gut microbiota can affect gut-brain communication and hence brain function.

Probiotic Mixture Containing Lactobacillus helveticus, Bifidobacterium longum and Lactiplantibacillus plantarum Affects Brain Responses Toward an Emotional Task in Healthy Subjects: A Randomized Clinical Trial.

Background: Evidence from preclinical studies suggests that probiotics affect brain function via the microbiome-gut-brain axis, but evidence in humans remains limited. Objective: The present proof-of-concept study investigated if a probiotic product containing a mixture of Bifidobacterium longum R0175, Lactobacillus helveticus R0052 and Lactiplantibacillus plantarum R1012 (in total 3 × 109 CFU/day) affected functional brain responses in healthy subjects during an emotional attention task. Design: In this double-blinded, randomized, placebo-controlled crossover study (Clinicaltrials.gov, NCT03615651), 22 healthy subjects (24.2 ± 3.4 years, 6 males/16 females) were exposed to a probiotic intervention and a placebo for 4 weeks each, separated by a 4-week washout period. Subjects underwent functional magnetic resonance imaging while performing an emotional attention task after each intervention period. Differential brain activity and functional connectivity were assessed. Results: Altered brain responses were observed in brain regions implicated in emotional, cognitive and face processing. Increased activation in the orbitofrontal cortex, a region that receives extensive sensory input and in turn projects to regions implicated in emotional processing, was found after probiotic intervention compared to placebo using a cluster-based analysis of functionally defined areas. Significantly reduced task-related functional connectivity was observed after the probiotic intervention compared to placebo. Fecal microbiota composition was not majorly affected by probiotic intervention. Conclusion: The probiotic intervention resulted in subtly altered brain activity and functional connectivity in healthy subjects performing an emotional task without major effects on the fecal microbiota composition. This indicates that the probiotic effects occurred via microbe-host interactions on other levels. Further analysis of signaling molecules could give possible insights into the modes of action of the probiotic intervention on the gut-brain axis in general and brain function specifically. The presented findings further support the growing consensus that probiotic supplementation influences brain function and emotional regulation, even in healthy subjects. Future studies including patients with altered emotional processing, such as anxiety or depression symptoms are of great interest. Clinical Trial Registration: [http://clinicaltrials.gov/], identifier [NCT03615651].

Probiotic Mixture Containing Lactobacillus helveticus, Bifidobacterium longum and Lactiplantibacillus plantarum Affects Brain Responses to an Arithmetic Stress Task in Healthy Subjects: A Randomised Clinical Trial and Proof-of-Concept Study.

Probiotics are suggested to impact physiological and psychological stress responses by acting on the gut-brain axis. We investigated if a probiotic product containing Bifidobacterium longum R0175, Lactobacillus helveticus R0052 and Lactiplantibacillus plantarum R1012 affected stress processing in a double-blinded, randomised, placebo-controlled, crossover proof-of-concept study (NCT03615651). Twenty-two healthy subjects (24.2 ± 3.4 years, 6 men/16 women) underwent a probiotic and placebo intervention for 4 weeks each, separated by a 4-week washout period. Subjects were examined by functional magnetic resonance imaging while performing the Montreal Imaging Stress Task (MIST) as well as an autonomic nervous system function assessment during the Stroop task. Reduced activation in regions of the lateral orbital and ventral cingulate gyri was observed after probiotic intervention compared to placebo. Significantly increased functional connectivity was found between the upper limbic region and medioventral area. Interestingly, probiotic intervention seemed to predominantly affect the initial stress response. Salivary cortisol secretion during the task was not altered. Probiotic intervention did not affect cognitive performance and autonomic nervous system function during Stroop. The probiotic intervention was able to subtly alter brain activity and functional connectivity in regions known to regulate emotion and stress responses. These findings support the potential of probiotics as a non-pharmaceutical treatment modality for stress-related disorders.

The use of Faecal Microbiota Transplantation (FMT) in Europe: A Europe-wide survey.

BACKGROUND: Faecal microbiota transplantation (FMT) is an emerging treatment modality, but its current clinical use and organisation are unknown. We aimed to describe the clinical use, conduct, and potential for FMT in Europe. METHODS: We invited all hospital-based FMT centres within the European Council member states to answer a web-based questionnaire covering their clinical activities, organisation, and regulation of FMT in 2019. Responders were identified from trials registered at clinicaltrials.gov and from the United European Gastroenterology (UEG) working group for stool banking and FMT. FINDINGS: In 2019, 31 FMT centres from 17 countries reported a total of 1,874 (median 25, quartile 10-64) FMT procedures; 1,077 (57%) with Clostridioides difficile infection (CDI) as indication, 791 (42%) with experimental indications, and 6 (0•3%) unaccounted for. Adjusted to population size, 0•257 per 100,000 population received FMT for CDI and 0•189 per 100,000 population for experimental indications. With estimated 12,400 (6,100-28,500) annual cases of multiple, recurrent CDI and indication for FMT in Europe, the current European FMT activity covers approximately 10% of the patients with indication. The participating centres demonstrated high safety standards and adherence to international consensus guidelines. Formal or informal regulation from health authorities was present at 21 (68%) centres. INTERPRETATION: FMT is a widespread routine treatment for multiple, recurrent CDI and an experimental treatment. Embedded within hospital settings, FMT centres operate with high standards across Europe to provide safe FMT. A significant gap in FMT coverage suggests the need to raise clinical awareness and increase the FMT activity in Europe by at least 10-fold to meet the true, indicated need. FUNDING: NordForsk under the Nordic Council and Innovation Fund Denmark (j.no. 8056-00006B).

Sauna dehydration as a new physiological challenge model for intestinal barrier function.

The intestinal barrier plays a crucial role in maintaining gut health, and an increased permeability has been linked to several intestinal and extra-intestinal disorders. There is an increasing demand for interventions aimed at strengthening this barrier and for in vivo challenge models to assess their efficiency. This study investigated the effect of sauna-induced dehydration on intestinal barrier function (clinicaltrials.gov: NCT03620825). Twenty healthy subjects underwent three conditions in random order: (1) Sauna dehydration (loss of 3% body weight), (2) non-steroidal anti-inflammatory drug (NSAID) intake, (3) negative control. Intestinal permeability was assessed by a multi-sugar urinary recovery test, while intestinal damage, bacterial translocation and cytokines were assessed by plasma markers. The sauna dehydration protocol resulted in an increase in gastroduodenal and small intestinal permeability. Presumably, this increase occurred without substantial damage to the enterocytes as plasma intestinal fatty acid-binding protein (I-FABP) and liver fatty acid-binding protein (L-FABP) were not affected. In addition, we observed significant increases in levels of lipopolysaccharide-binding protein (LBP), IL-6 and IL-8, while sCD14, IL-10, IFN-É£ and TNF-α were not affected. These results suggest that sauna dehydration increased intestinal permeability and could be applied as a new physiological in vivo challenge model for intestinal barrier function.

Short intense psychological stress induced by skydiving does not impair intestinal barrier function.

BACKGROUND AND AIM: Psychological stress has been shown to increase intestinal permeability and is associated with the development of gastrointestinal disorders. This study aimed to investigate skydiving as an alternative model to analyse the effect of acute psychological stress on intestinal barrier function. MATERIALS AND METHODS: Twenty healthy subjects participated in a tandem skydive followed by a negative control visit, of which 19 (9 females and 10 males, 25.9 ± 3.7 years) were included in the study. Intestinal permeability was assessed by a multi-sugar urinary recovery test. Sucrose recovery and lactulose/rhamnose ratio in 0-5h urine indicated gastroduodenal and small intestinal permeability, respectively, and sucralose/erythritol ratio in 5-24h urine indicated colonic permeability. Blood samples were taken to assess markers associated with barrier function. This study has been registered at ClinicalTrials.gov (NCT03644979) on August 23, 2018. RESULTS: Skydiving resulted in a significant increase in salivary cortisol levels directly after skydiving compared to the control visit. Cortisol levels were still increased two hours after landing, while cortisol levels before skydiving were not significantly different from the baseline at the control visit. Skydiving did not induce a significant increase in gastroduodenal, small intestinal or colonic permeability. There was also no significant increase in plasma intestinal and liver fatty acid-binding proteins, suggesting no damage to the enterocytes. DISCUSSION: These results show that the acute intense psychological stress induced by skydiving does not affect intestinal permeability in healthy subjects. Future models aiming to investigate the effect of stress on human intestinal barrier function should consider a more sustained exposure to the psychological stressor.

Feasibility and Acceptability of a Healthy Nordic Diet Intervention for the Treatment of Depression: A Randomized Controlled Pilot Trial.

Healthy diet interventions have been shown to improve depressive symptoms, but there is a need for randomized controlled trials (RCTs) that are double blind and investigate biological mechanisms. The primary objectives of this randomized controlled pilot trial were to test the palatability of the meals and the acceptability of the intervention in preparation for an 8-week RCT in the future, which will investigate whether a healthy Nordic diet improves depressive symptoms in individuals with major depressive disorder, and associated biological mechanisms. Depressed (n = 10) and non-depressed (n = 6) women and men were randomized to receive either a healthy Nordic diet (ND) or a control diet (CD) for 8 days. Participants were blinded to their diet allocation and the study hypotheses. Health questionnaires were completed before and after the intervention and, throughout the study, questionnaires assessed participants' liking for the meals, their sensory properties, adherence, and open-ended feedback. In the ND group, 75% of participants consumed only the provided foods, as instructed, compared to 50% of CD participants. The meals of both diets, on average, received good ratings for liking and sensory properties, though the ND ratings were somewhat higher. Overall, results were positive and informative, indicating that the planned RCT will be feasible and well-accepted, with some proposed modifications.

Differences in Gut Microbiome Composition between Senior Orienteering Athletes and Community-Dwelling Older Adults.

BACKGROUND: Gastrointestinal (GI) health is an important aspect of general health. Gastrointestinal symptoms are of specific importance for the elderly, an increasing group globally. Hence, promoting the elderly's health and especially gastrointestinal health is important. Gut microbiota can influence gastrointestinal health by modulation of the immune system and the gut-brain axis. Diverse gut microbiota have been shown to be beneficial; however, for the elderly, the gut microbiota is often less diverse. Nutrition and physical activity, in particular, are two components that have been suggested to influence composition or diversity. MATERIALS AND METHODS: In this study, we compared gut microbiota between two groups of elderly individuals: community-dwelling older adults and physically active senior orienteering athletes, where the latter group has less gastrointestinal symptoms and a reported better well-being. With this approach, we explored if certain gut microbiota were related to healthy ageing. The participant data and faecal samples were collected from these two groups and the microbiota was whole-genome sequenced and taxonomically classified with MetaPhlAn. RESULTS: The physically active senior orienteers had a more homogeneous microbiota within the group and a higher abundance of Faecalibacterium prausnitzii compared to the community-dwelling older adults. Faecalibacterium prausnitzii has previously shown to have beneficial properties. Senior orienteers also had a lower abundance of Parasutterella excrementihominis and Bilophila unclassified, which have been associated with impaired GI health. We could not observe any difference between the groups in terms of Shannon diversity index. Interestingly, a subgroup of community-dwelling older adults showed an atypical microbiota profile as well as the parameters for gastrointestinal symptoms and well-being closer to senior orienteers. CONCLUSIONS: Our results suggest specific composition characteristics of healthy microbiota in the elderly, and show that certain components of nutrition as well as psychological distress are not as tightly connected with composition or diversity variation in faecal microbiota samples.

Effects of Dietary Fibres on Acute Indomethacin-Induced Intestinal Hyperpermeability in the Elderly: A Randomised Placebo Controlled Parallel Clinical Trial.

The effect of dietary fibres on intestinal barrier function has not been well studied, especially in the elderly. We aimed to investigate the potential of the dietary fibres oat ß-glucan and wheat arabinoxylan to strengthen the intestinal barrier function and counteract acute non-steroid anti-inflammatory drug (indomethacin)-induced hyperpermeability in the elderly. A general population of elderly subjects (≥65 years, n = 49) was randomised to a daily supplementation (12g/day) of oat ß-glucan, arabinoxylan or placebo (maltodextrin) for six weeks. The primary outcome was change in acute indomethacin-induced intestinal permeability from baseline, assessed by an in vivo multi-sugar permeability test. Secondary outcomes were changes from baseline in: gut microbiota composition, systemic inflammatory status and self-reported health. Despite a majority of the study population (85%) showing a habitual fibre intake below the recommendation, no significant effects on acute indomethacin-induced intestinal hyperpermeability in vivo or gut microbiota composition were observed after six weeks intervention with either dietary fibre, compared to placebo.

Acute Effects of Butyrate on Induced Hyperpermeability and Tight Junction Protein Expression in Human Colonic Tissues.

Intact intestinal barrier function is essential for maintaining intestinal homeostasis. A dysfunctional intestinal barrier can lead to local and systemic inflammation through translocation of luminal antigens and has been associated with a range of health disorders. Butyrate, a short-chain fatty acid derived from microbial fermentation of dietary fibers in the colon, has been described as an intestinal barrier-strengthening agent, although mainly by using in vitro and animal models. This study aimed to investigate butyrate's ability to prevent intestinal hyperpermeability, induced by the mast cell degranulator Compound 48/80 (C48/80), in human colonic tissues. Colonic biopsies were collected from 16 healthy subjects and intestinal permeability was assessed by Ussing chamber experiments. Furthermore, the expression levels of tight junction-related proteins were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Pre-treatment with 5 mM butyrate or 25 mM butyrate did not protect the colonic tissue against induced paracellular or transcellular hyperpermeability, measured by FITC-dextran and horseradish peroxidase passage, respectively. Biopsies treated with 25 mM butyrate prior to stimulation with C48/80 showed a reduced expression of claudin 1. In conclusion, this translational ex vivo study did not demonstrate an acute protective effect of butyrate against a chemical insult to the intestinal barrier in healthy humans.

Meal patterns in relation to energy and protein intake in older adults in home health care.

BACKGROUND & AIMS: Inadequate dietary intake is common in frail elderly people, however knowledge of meal patters and their relation to dietary intake is scarce, but is important for planning meals and nutritional prevention and interventions. The aim of this study was to describe meal patterns and the relation to energy and protein intake in elderly people in home health care. METHODS: In this cross-sectional study, 69 men and women ≥65 years old with a lasting need for home health care were included. A 24-hour recall was used to analyse meal patterns as well as intake of energy and protein. Meal patterns were analysed in terms of number of eating occasions, time of the first, and the last meal each day, length of the overnight fast, timing of the energy and protein intake, energy content and time for the largest meal of the day, and classification as an early or late eater. RESULTS: In this population, 77% had four or five eating occasions per day. The median length of the overnight fast was 13 h and 87% of participants had an overnight fast of >11 h. Regarding the timing of the energy and protein intake, there were three peaks: in the morning, mid-day and in the evening. The mid-day meal was the most important eating occasion regarding total energy intake; mid-day was also the time of the day when most participants had a protein intake >20 g. The majority (60%) of participants were categorized as early eaters. Neither the number of eating occasions nor the length of the overnight fast was correlated with energy or protein intake; however, a large energy intake from the largest meal of the day was significantly correlated with an increased total energy and protein intake, indicating that daily energy intake is stimulated by at least one large meal per day. CONCLUSIONS: This study showed that one large meal a day had more impact on daily energy and protein intake than did several eating occasions or a short overnight fast in elderly people in home health care. Further research is needed to elucidate how to stimulate large energy intake at main meals to stimulate daily energy and protein intake.

Allogenic Faecal Microbiota Transfer Induces Immune-Related Gene Sets in the Colon Mucosa of Patients with Irritable Bowel Syndrome.

Faecal microbiota transfer (FMT) consists of the introduction of new microbial communities into the intestine of a patient, with the aim of restoring a disturbed gut microbiota. Even though it is used as a potential treatment for various diseases, it is unknown how the host mucosa responds to FMT. This study aims to investigate the colonic mucosa gene expression response to allogenic (from a donor) or autologous (own) FMT in patients with irritable bowel syndrome (IBS). In a recently conducted randomised, double-blinded, controlled clinical study, 17 IBS patients were treated with FMT by colonoscopy. RNA was isolated from colonic biopsies collected by sigmoidoscopy at baseline, as well as two weeks and eight weeks after FMT. In patients treated with allogenic FMT, predominantly immune response-related gene sets were induced, with the strongest response two weeks after the FMT. In patients treated with autologous FMT, predominantly metabolism-related gene sets were affected. Furthermore, several microbiota genera showed correlations with immune-related gene sets, with different correlations found after allogenic compared to autologous FMT. This study shows that the microbe-host response is influenced by FMT on the mucosal gene expression level, and that there are clear differences in response to allogenic compared to autologous FMT.

The Effect of Allogenic Versus Autologous Fecal Microbiota Transfer on Symptoms, Visceral Perception and Fecal and Mucosal Microbiota in Irritable Bowel Syndrome: A Randomized Controlled Study.

OBJECTIVES: Fecal microbiota transfer (FMT) is suggested as a potential treatment for patients with irritable bowel syndrome (IBS). We aimed to study the effect of allogenic and autologous FMT on IBS symptoms, visceral sensitivity, and compositional changes in fecal and mucosa-adherent microbiota. METHODS: Seventeen patients with IBS were randomized either to receive fecal material from a healthy donor (allogenic) or to receive their own fecal material (autologous). The fecal material was administered into the cecum by whole colonoscopy after bowel cleansing. RESULTS: No significant differences were found between the allogenic and the autologous FMT regarding symptom scores. However, symptom scores of patients receiving allogenic fecal material significantly decreased after FMT compared with baseline (P = 0.02), which was not the case in the autologous group (P = 0.16). Visceral sensitivity was not affected except for a small beneficial effect on urge scores in the autologous group (P < 0.05). While both fecal and mucosa-adherent microbiota of some patients shifted to their respective donor's fecal microbiota, some patients showed no relevant microbial changes after allogenic FMT. Large compositional shifts in fecal and mucosa-adherent microbiota also occurred in the autologous group. CONCLUSIONS: This study showed that a single FMT by colonoscopy may have beneficial effects in IBS; however, the allogenic fecal material was not superior to the autologous fecal material. This suggests that bowel cleansing prior to the colonoscopy and/or processing of the fecal material as part of the FMT routine contribute to symptoms and gut microbiota composition changes in IBS.

ADHD-originating in the gut? The emergence of a new explanatory model.

The microbiome-gut-brain axis paradigm explains that alterations in the central nervous system and behavior may be secondary to functional changes in the gut in general and more specifically the enteric nervous system. An unfavorable development of the intestinal microbial ecosystem, leading to e.g. a diminished microbial diversity, may play a central role. This paper outlines, and describes the theoretical basis of, a novel integrative model explaining the etiology and pathogenesis of ADHD in a microbiota-gut-brain context, taking into account the complexity of the bi-directional signaling between the gut and the brain.