Fecal bacteria and short-chain fatty acids in irritable bowel syndrome: Relations to subtype.

BACKGROUND: The relationship between gut microbiota and irritable bowel syndrome (IBS) subtype is unclear. We aimed to explore whether differences in fecal bacteria composition and short-chain fatty acid (SCFA) levels were associated with subtypes and symptoms of IBS. METHODS: All participants delivered fecal samples and self-reports on IBS Symptom Severity Score (IBS-SSS), Bristol Stool Scale (BSS), and Gastrointestinal Symptom Rating Scale (GSRS). Fecal bacteria composition was assessed by the GA-map® Dysbiosis Test based on 16S rRNA sequences of bacterial species/groups. SCFAs were analyzed by vacuum distillation followed by gas chromatography. KEY RESULTS: Sixty patients with IBS were included (mean age 38 years, 46 [77%] females): Twenty-one patients were classified as IBS-D (diarrhea), 31 IBS-M (mixed diarrhea and constipation), and eight IBS-C (constipation). Forty-two healthy controls (HCs) (mean age 35 years, 27 [64%] females) were included. Patients had a significantly higher relative frequency of dysbiosis, lower levels of Actinobacteria, and higher levels of Bacilli than HCs. Eight bacterial markers were significantly different across IBS subgroups and HCs, and 13 bacterial markers were weakly correlated with IBS symptoms. Clostridia and Veillonella spp. had a weak negative correlation with constipation scores (GSRS) and a weak positive correlation with loose stools (BSS). Diarrhea scores (GSRS) and looser stool (BSS) were weakly correlated with levels of total SCFAs, acetic and butyric acid. Levels of total SCFAs and acetic acid were weakly correlated with symptom severity (IBS-SSS). CONCLUSIONS & INFERENCES: Patients with IBS had a different fecal bacteria composition compared to HCs, and alterations of SCFAs may contribute to the subtype.

Dietary intake and nutritional status in patients with newly diagnosed inflammatory bowel disease: insights from the IBSEN III study.

BACKGROUND: Dietary recommendations in inflammatory bowel disease (IBD) are inconclusive, and patients may follow restrictive diets with increased risk of malnutrition. The aim of this study was to compare dietary intakes and nutritional status in men and women with newly diagnosed IBD with a general population sample, and to investigate whether intakes were in line with the Nordic Nutrition Recommendations. METHODS: This was a cross-sectional study including adults≥ 40 years with IBD from the Inflammatory Bowel Disease in South-Eastern Norway (IBSEN) III cohort study. A validated food frequency questionnaire (FFQ) was used in dietary data collection, and a sample from the seventh survey of the Tromsø Study was included as a comparison group. RESULTS: A total of 227 men and women with IBD were included. IBD patients had higher intake of grain products, sweetened beverages, energy, fat and polyunsaturated fat (PUFA), but lower intake of dairy products, alcohol and iodine compared to adults from the comparison sample (p < 0.01). Intakes of saturated fat and carbohydrates in both genders, and vitamin D in women were not within recommended levels. Anemia and hypoalbuminemia were more prevalent in IBD patients than in the comparison sample. CONCLUSIONS: Dietary intakes in newly diagnosed IBD patients were mostly in line with Nordic Nutrition Recommendations. Higher proportion of IBD patients exceeded recommended allowances of fat and added sugar than the comparison sample. Insufficient micronutrient intake, anemia and hypoalbuminemia are present challenges in IBD patients that require monitoring.

Self-prescribed dietary restrictions in patients with inflammatory bowel disease (IBD) due to inconclusive dietary guidance may influence their risk of malnutrition. Comprehensive assessment of both dietary intake and nutritional status as early as time of diagnosis may help identify challenges in this patient group and implement appropriate interventions.

Diet-microbiota interaction in irritable bowel syndrome: looking beyond the low-FODMAP approach.

BACKGROUND: Diet is one of the main modulators of the gut microbiota, and dietary patterns are decisive for gut-microbiota-related diseases, including irritable bowel syndrome (IBS). The low-FODMAP diet (LFD) is commonly used to treat IBS, but its long-term effects on microbiota, symptoms and quality of life (QoL) are unclear. Alternative dietary strategies promoting beneficial gut microbiota, combined with reduced symptoms and improved QoL, are therefore of interest. AIMS: To review current evidence on the diet-microbiota-interaction as a modulator of IBS pathophysiology, and dietary management of IBS, with particular emphasis on strategies targeting the gut microbiota, beyond the LFD. METHODS: Literature was identified through PubMed-searches with relevant keywords. RESULTS: Dietary patterns with a low intake of processed foods and a high intake of plants, such as the Mediterranean diet, promote gut microbiota associated with beneficial health outcomes. In contrast, Western diets with a high intake of ultra-processed foods promote a microbiota associated with disease, including IBS. Increasing evidence points towards dietary strategies consistent with the Mediterranean diet being equal to the LFD in alleviating IBS-symptoms and having a less negative impact on QoL. Timing of food intake is suggested as a gut microbiota modulator, but little is known about its effects on IBS. CONCLUSIONS: Dietary recommendations in IBS should aim to target the gut microbiota by focusing on improved dietary quality, considering the impact on both IBS-symptoms and QoL. Increased intake of whole foods combined with a regular meal pattern and limitation of ultra-processed foods can be beneficial strategies beyond the LFD.

Effects of a low FODMAP diet on gut microbiota in individuals with treated coeliac disease having persistent gastrointestinal symptoms - a randomised controlled trial.

Individuals with coeliac disease (CeD) often experience gastrointestinal symptoms despite adherence to a gluten-free diet (GFD). While we recently showed that a diet low in fermentable oligo-, di-, monosaccharides and polyols (FODMAP) successfully provided symptom relief in GFD-treated CeD patients, there have been concerns that the low FODMAP diet (LFD) could adversely affect the gut microbiota. Our main objective was therefore to investigate whether the LFD affects the faecal microbiota and related variables of gut health. In a randomised controlled trial GFD-treated CeD adults, having persistent gastrointestinal symptoms, were randomised to either consume a combined LFD and GFD (n 39) for 4 weeks or continue with GFD (controls, n 36). Compared with the control group, the LFD group displayed greater changes in the overall faecal microbiota profile (16S rRNA gene sequencing) from baseline to follow-up (within-subject ß-diversity, P < 0·001), characterised by lower and higher follow-up abundances (%) of genus Anaerostipes (Pgroup < 0·001) and class Erysipelotrichia (Pgroup = 0·02), respectively. Compared with the control group, the LFD led to lower follow-up concentrations of faecal propionic and valeric acid (GC-FID) in participants with high concentrations at baseline (Pinteraction ≤ 0·009). No differences were found in faecal bacterial α-diversity (Pgroup ≥ 0·20) or in faecal neutrophil gelatinase-associated lipocalin (ELISA), a biomarker of gut integrity and inflammation (Pgroup = 0·74), between the groups at follow-up. The modest effects of the LFD on the gut microbiota and related variables in the CeD patients of the present study are encouraging given the beneficial effects of the LFD strategy to treat functional GI symptoms (Registered at clinicaltrials.gov as NCT03678935).

Increased plasma levels of non-sugar sweeteners in patients with symptomatic carotid atherosclerosis.

Purpose. The non-sugar sweeteners acesulfame K and saccharin are considered safe, but there is conflicting evidence on their effects on cardiovascular health. Materials and methods. In this explorative pilot study, we measured plasma levels of acesulfame K and saccharin in 15 patients with symptomatic carotid atherosclerosis, 18 asymptomatic patients and 15 control subjects. Fecal microbiota and short-chain fatty acids were analyzed. Dietary and medical history was assessed. Results. Symptomatic patients had higher levels of acesulfame K and saccharin compared to controls. Acesulfame K was associated with increased leukocyte count. Saccharin was associated with more severe carotid stenosis, as well as lower fecal butyric acid.

Short-chain fatty acids as a link between diet and cardiometabolic risk: a narrative review.

AIM: Diet has a profound impact on cardiometabolic health outcomes such as obesity, blood glucose, blood lipids and blood pressure. In recent years, the gut microbiota has emerged as one of several potential key players explaining dietary effects on these outcomes. In this review we aim to summarise current knowledge of interaction between diet and gut microbiota focusing on the gut-derived microbial metabolites short-chain fatty acids and their role in modulating cardiometabolic risk. FINDINGS: Many observational and interventional studies in humans have found that diets rich in fibre or supplemented with prebiotic fibres have a favourable effect on the gut microbiota composition, with increased diversity accompanied by enhancement in short-chain fatty acids and bacteria producing them. High-fat diets, particularly diets high in saturated fatty acids, have shown the opposite effect. Several recent studies indicate that the gut microbiota modulates metabolic responses to diet in, e.g., postprandial blood glucose and blood lipid levels. However, the metabolic responses to dietary interventions, seem to vary depending on individual traits such as age, sex, ethnicity, and existing gut microbiota, as well as genetics. Studies mainly in animal models and cell lines have shown possible pathways through which short-chain fatty acids may mediate these dietary effects on metabolic regulation. Human intervention studies appear to support the favourable effect of short-chain fatty acid in animal studies, but the effects may be modest and vary depending on which cofactors were taken into consideration. CONCLUSION: This is an expanding and active field of research that in the near future is likely to broaden our understanding of the role of the gut microbiota and short-chain fatty acids in modulating metabolic responses to diet. Nevertheless, the findings so far seem to support current dietary guidelines encouraging the intake of fibre rich plant-based foods and discouraging the intake of animal foods rich in saturated fatty acids.

Fecal level of butyric acid, a microbiome-derived metabolite, is increased in patients with severe carotid atherosclerosis.

The short-chain fatty acid (SCFA) butyric acid maintains a healthy gut barrier and vascular endothelium. We aimed to investigate the association between fecal butyric acid, carotid atherosclerosis and risk factors for ischemic stroke. Patients with severe carotid atherosclerosis (i.e. ≥ 50% stenosis) (n = 43) were compared with healthy controls (n = 38). We analyzed fecal SCFAs by gas chromatography, microbiota composition by 16S rRNA sequencing, markers of gut barrier damage and inflammasome activation by immunoassay, and plasma SCFAs by ultra-high performance liquid chromatography-tandem mass spectroscopy. Patients had higher fecal butyric acid level (p = 0.024), along with increased functional potential of microbial butyric acid production (p = 0.031), compared with controls. Dietary fiber intake was comparable. Patients had higher levels of gut barrier damage markers CCL25 and IFABP, and the inflammasome activation marker IL-18, whereas plasma level of butyric was similar. Increased fecal butyric acid was associated with higher BMI, waist-hip ratio, HbA1c, CRP and leukocyte count. Contrary to our hypothesis, patients with severe carotid atherosclerosis had higher fecal butyric acid level, and increased microbial production, compared with controls. Gut barrier damage in patients might indicate decreased absorption of butyric acid and hence contribute to the higher fecal level.

Associations Between Intrathecal Levels of Vitamin D, Cytokines, and Core Biomarkers of Alzheimer's Disease: A Cross-Sectional Study.

BACKGROUND: Several studies have examined association between vitamin D levels in serum and cognition, but little is known of vitamin D levels in cerebrospinal fluid (CSF) and association with Alzheimer's disease (AD). OBJECTIVE: In this cross-sectional, explorative study we investigated possible associations of vitamin D in CSF with biomarkers for AD, amyloid-ß, tau protein/phosphorylated tau protein in CSF, and with the cytokines IL-6, IL-8, and TNF-α in CSF in patients with cognitive impairment and cognitively healthy controls. METHODS: We included 100 outpatients ≥65 years referred for assessment of cognitive impairment and 76 age- and sex-matched cognitively healthy controls. Levels of 25-hydroxyvitamin D (25(OH)D), amyloid-ß, tau protein and phosphorylated tau protein, as well as IL-6, IL-8, and TNF-α, were analyzed in CSF in both groups. RESULTS: Higher levels of 25(OH)D in CSF in all groups together were associated with lower levels of tau protein (p = 0.01) and phosphorylated tau protein (p = 0.005). We found no association between 25(OH)D levels in CSF and pathological levels of amyloid-ß in CSF nor levels of IL-6 or TNF-α in CSF. Higher levels of 25(OH)D in CSF were associated with higher levels of IL-8 in CSF (p = 0.002). However, vitamin D explained only 6% of variance in IL-8. There was no significant difference between the patient groups and the control group regarding the association between 25(OH)D in CSF and any of the three cytokines in CSF. CONCLUSION: Participants with higher CSF levels of 25(OH)D exhibited reduced CSF levels of tau protein and phosphorylated tau protein.

Vitamin D in Alzheimer's Disease: Low Levels in Cerebrospinal Fluid Despite Normal Amounts in Serum.

BACKGROUND: Vitamin D insufficiency has been suggested as a dementia risk factor. OBJECTIVE: In this cross-sectional, explorative study we investigated whether levels of vitamin D in cerebrospinal fluid (CSF) are lower in patients with positive biomarkers of Alzheimer's disease (AD) compared to cognitively healthy controls and whether polymorphisms of the vitamin D receptor (VDR) gene, FokI, BsmI, ApaI, and TaqI, are associated with levels of vitamin D in CSF and cognition. METHODS: We included 100 patients≥65 years assessed for cognitive impairment and 76 cognitively healthy controls. Levels of 25-hydroxyvitamin D (25(OH)D) in both serum and CSF, and VDR polymorphisms were analyzed. RESULTS: The mean level of 25(OH)D in serum was 78.6 (SD 28.9) nmol/l. While serum levels of 25(OH)D were not significantly different between the groups, CSF levels of 25(OH)D were significantly lower in patients with positive AD core biomarkers (p = 0.001) compared to patients without such biomarkers. Individuals with the BsmI major homozygote genotype had significantly lower results on a 10-word delayed recall test (p = 0.044) and verbal fluency test (p = 0.013), and individuals with the TaqI major homozygote genotype had significantly lower results on a verbal fluency test (p = 0.030) compared to individuals with the corresponding minor homozygote genotype. CONCLUSION: Patients with positive AD core biomarkers have low CSF levels of 25(OH)D, despite sufficient serum levels. CSF levels of 25(OH)D do not seem to be affected by any of the four VDR gene polymorphisms. TaqI and BsmI major homozygote genotypes might be at increased risk for development of cognitive decline.

Long-term effects of fecal microbiota transplantation (FMT) in patients with irritable bowel syndrome.

BACKGROUND: We recently found fecal microbiota transplantation (FMT) in irritable bowel syndrome (IBS) patients to be an effective and safe treatment after 3 months. The present follow-up study investigated the efficacy and safety of FMT at 1 year after treatment. METHODS: This study included 77 of the 91 IBS patients who had responded to FMT in our previous study. Patients provided a fecal sample and completed five questionnaires to assess their symptoms and quality of life at 1 year after FMT. The dysbiosis index (DI) and fecal bacterial profile were analyzed using a 16S rRNA gene-based DNA probe hybridization. The levels of fecal short-chain fatty acids (SCFAs) were determined by gas chromatography. RESULTS: There was a persistent response to FMT at 1 year after treatment in 32 (86.5%) and 35 (87.5%) patients who received 30-g and 60-g FMT, respectively. In the 30-g FMT group, 12 (32.4%) and 8 (21.6%) patients showed complete remission at 1 year and 3 months, respectively; the corresponding numbers in the 60-g FMT group were 18 (45%) and 11 (27.5%), respectively. Abdominal symptoms and the quality of life were improved at 1 year compared with after 3 months. These findings were accompanied by comprehensive changes in the fecal bacterial profile and SCFAs. CONCLUSIONS: Most of the IBS patients maintained a response at 1 year after FMT. Moreover, the improvements in symptoms and quality of life increased over time. Changes in DI, fecal bacterial profile and SCFAs were more comprehensive at 1 year than after 3 months. www.clinicaltrials.gov (NCT03822299).

Mortality and microbial diversity after allogeneic hematopoietic stem cell transplantation: secondary analysis of a randomized nutritional intervention trial.

Gut mucosal barrier injury is common following allogeneic hematopoietic stem cell transplantation (allo-HSCT) and associated with poor clinical outcomes. Diet is critical for microbial diversity, but whether nutritional support affects microbiota and outcome after allo-HSCT is unknown. We present a secondary analysis of a randomized controlled nutritional intervention trial during allo-HSCT. We investigated if the intervention influenced gut microbiota, short-chain fatty acids (SCFAs), and markers of gut barrier functions, and if these parameters were associated with clinical outcomes. Fecal specimens were available from 47 recipients, and subjected to 16S rRNA gene sequencing. We found no significant differences between the intervention group and controls in investigated parameters. We observed a major depletion of microbiota, SCFAs, and altered markers of gut barrier function from baseline to 3 weeks post-transplant. One-year mortality was significantly higher in patients with lower diversity at 3 weeks post-HSCT, but not related to diversity at baseline. The relative abundance of Blautia genus at 3 weeks was higher in survivors. Fecal propionic acid was associated with survival. Markers of gut barrier functions were less strongly associated with clinical outcomes. Possibly, other strategies than dietary intervention are needed to prevent negative effects of gut microbiota and clinical outcomes after allo-HSCT.ClinicalTrials.gov (NCT01181076).

Responses to faecal microbiota transplantation in female and male patients with irritable bowel syndrome.

BACKGROUND: Faecal microbiota transplantation (FMT) seems to be a promising treatment for irritable bowel syndrome (IBS) patients. In Western countries (United States and Europe), there is a female predominance in IBS. A sex difference in the response to FMT has been reported recently in IBS patients. AIM: To investigate whether there was a sex difference in the response to FMT in the IBS patients who were included in our previous randomized controlled trial of the efficacy of FMT. METHODS: The study included 164 IBS patients who participated in our previous randomized controlled trial. These patients had moderate-to-severe IBS symptoms belonging to the IBS-D (diarrhoea-predominant), IBS-C (constipation-predominant) and IBS-M (mixed) subtypes, and had not responded to the National Institute for Health and Care Excellence (NICE)-modified diet. They belonged in three groups: placebo (own faeces), and active treated group (30-g or 60-g superdonor faeces). The patients completed the IBS severity scoring system (IBS-SSS), Fatigue Assessment Scale (FAS) and the IBS quality of life scale (IBS-QoL) questionnaires at the baseline and 2 wk, 1 mo and 3 mo after FMT. They also provided faecal samples at the baseline and 1 mo after FMT. The faecal bacteria profile and dysbiosis were determined using the 16S rRNA gene polymerase chain reaction DNA amplification covering V3-V9; probe labelling by single nucleotide extension and signal detection. The levels of short-chain fatty acids (SCFAs) were determined by gas chromatography and flame ionization. RESULTS: There was no sex difference in the response to FMT either in the placebo group or active treated group. There was no difference between females and males in either the placebo group or actively treated groups in the total score on the IBS-SSS, FAS or IBS-QoL, in dysbiosis, or in the faecal bacteria or SCFA level. However, the response rate was significantly higher in females with diarrhoea-predominant (IBS-D) than that of males at 1 mo, and 3 mo after FMT. Moreover, IBS-SSS total score was significantly lower in female patients with IBS-D than that of male patients both 1 mo and 3 mo after FMT. CONCLUSION: There was no sex difference in the response to FMT among IBS patients with moderate-to-severe symptoms who had previously not responded to NICE-modified diet. However, female patients with IBS-D respond better and have higher reduction of symptoms than males after FMT.

Changes in fecal short-chain fatty acids following fecal microbiota transplantation in patients with irritable bowel syndrome.

BACKGROUND: Short-chain fatty acids (SCFAs) may play a role in the pathophysiology of irritable bowel syndrome (IBS). This study analyzed fecal SCFAs after performing fecal microbiota transplantation (FMT) in the IBS patients who were included in our previous study of the efficacy of FMT. METHODS: This study included 142 of the 164 IBS patients who participated in our previous study. They were belonging to three groups: placebo (own feces), 30-g (superdonor feces), and 60-g (superdonor feces) FMT. The patients completed the IBS Severity Scoring System (IBS-SSS) Birmingham IBS Symptom, Fatigue Assessment Scale (FAS), the IBS Quality of Life (IBS-QoL) and Short-Form Nepean Dyspepsia Index (SF-NDI) questionnaires and delivered fecal samples at the baseline and 1 month after FMT. The SCFA levels were determined by vacuum distillation followed by gas chromatography. KEY RESULTS: The fecal butyric acid level was significantly increased after FMT in both the 30-g and 60-g groups (both P ≤ 0.001). In the 60-g group, the levels of total SCFAs and isobutyric, isovaleric, and valeric acids increased after FMT. Butyric acid levels in the responders in both the 30-g and 60-g FMT groups were significantly inversely correlated with IBS-SSS and FAS scores (P = 0.001, r = -0.3 and P = 0.0001. r=- 0.3, respectively). There were no differences in the SCFA levels in the placebo group after FMT. CONCLUSION AND INFERENCES: FMT increases the fecal SCFA levels in IBS patients. The increase in the butyric acid level is inversely correlated with symptoms in IBS patients following FMT, suggesting that SCFAs might play a role in the pathophysiology of IBS. www.clini​caltr​ials.gov (NCT03822299).

Study protocol of the Bergen brain-gut-microbiota-axis study: A prospective case-report characterization and dietary intervention study to evaluate the effects of microbiota alterations on cognition and anatomical and functional brain connectivity in patients with irritable bowel syndrome.

INTRODUCTION: Irritable bowel syndrome (IBS) is a common clinical label for medically unexplained gastrointestinal (GI) symptoms, recently described as a disturbance of the brain-gut-microbiota (BGM) axis. To gain a better understanding of the mechanisms underlying the poorly understood etiology of IBS, we have designed a multifaceted study that aim to stratify the complex interaction and dysfunction between the brain, the gut, and the microbiota in patients with IBS. METHODS: Deep phenotyping data from patients with IBS (n = 100) and healthy age- (between 18 and 65) and gender-matched controls (n = 40) will be collected between May 2019 and December 2021. Psychometric tests, questionnaires, human biological tissue/samples (blood, faeces, saliva, and GI biopsies from antrum, duodenum, and sigmoid colon), assessment of gastric accommodation and emptying using transabdominal ultrasound, vagal activity, and functional and structural magnetic resonance imaging (MRI) of the brain, are included in the investigation of each participant. A subgroup of 60 patients with IBS-D will be further included in a 12-week low FODMAP dietary intervention-study to determine short and long-term effects of diet on GI symptoms, microbiota composition and functions, molecular GI signatures, cognitive, emotional and social functions, and structural and functional brain signatures. Deep machine learning, prediction tools, and big data analyses will be used for multivariate analyses allowing disease stratification and diagnostic biomarker detection. DISCUSSION: To our knowledge, this is the first study to employ unsupervised machine learning techniques and incorporate systems-based interactions between the central and the peripheral components of the brain-gut-microbiota axis at the levels of the multiomics, microbiota profiles, and brain connectome of a cohort of 100 patients with IBS and matched controls; study long-term safety and efficacy of the low-FODMAP diet on changes in nutritional status, gut microbiota composition, and metabolites; and to investigate changes in the brain and gut connectome after 12 weeks strict low-FODMAP-diet in patients with IBS. However, there are also limitations to the study. As a restrictive diet, the low-FODMAP diet carries risks of nutritional inadequacy and may foster disordered eating patterns. Strict FODMAP restriction induces a potentially unfavourable gut microbiota, although the health effects are unknown. TRIAL REGISTRATION NUMBER: NCT04296552 (ClinicalTrials.gov).

Correction to: Prebiotic effect of inulin­type fructans on faecal microbiota and short­chain fatty acids in type 2 diabetes: a randomised controlled trial.

The original version of this article unfortunately contained a mistake. The presentation of Fig. 4 was incorrect.

Fecal microbiota transplantation in systemic sclerosis: A double-blind, placebo-controlled randomized pilot trial.

OBJECTIVES: Systemic sclerosis (SSc) is an auto-immune, multi organ disease marked by severe gastrointestinal (GI) involvement and gut dysbiosis. Here, we aimed to determine the safety and efficacy of fecal microbiota transplantation (FMT) using commercially-available anaerobic cultivated human intestinal microbiota (ACHIM) in SSc. METHODS: Ten patients with SSc were randomized to ACHIM (n = 5) or placebo (n = 5) in a double-blind, placebo-controlled 16-week pilot. All patients had mild to severe upper and lower GI symptoms including diarrhea, distention/bloating and/or fecal incontinence at baseline. Gastroduodenoscopy transfer of ACHIM or placebo was performed at weeks 0 and 2. Primary endpoints were safety and clinical efficacy on GI symptoms assessed at weeks 4 and 16. Secondary endpoints included changes in relative abundance of total, immunoglobulin (Ig) A- and IgM-coated fecal bacteria measured by 16s rRNA sequencing. RESULTS: ACHIM side effects were mild and transient. Two placebo controls experienced procedure-related serious adverse events; one developed laryngospasms at week 0 gastroduodenoscopy necessitating study exclusion whilst one encountered duodenal perforation during gastroduodenoscopy at the last study visit (week 16). Decreased bloating, diarrhea and/or fecal incontinence was observed in four of five patients in the FMT group (week 4 or/and 16) and in two of four in the placebo group (week 4 or 16). Relative abundance, richness and diversity of total and IgA-coated and IgM-coated bacteria fluctuated more after FMT, than after placebo. CONCLUSIONS: FMT of commercially-available ACHIM is associated with gastroduodenoscopy complications but reduces lower GI symptoms by possibly altering the gut microbiota in patients with SSc.

Prebiotic effect of inulin-type fructans on faecal microbiota and short-chain fatty acids in type 2 diabetes: a randomised controlled trial.

PURPOSE: Compared to a healthy population, the gut microbiota in type 2 diabetes presents with several unfavourable features that may impair glucose regulation. The aim of this study was to evaluate the prebiotic effect of inulin-type fructans on the faecal microbiota and short-chain fatty acids (SCFA) in patients with type 2 diabetes. METHODS: The study was a placebo controlled crossover study, where 25 patients (15 men) aged 41-71 years consumed 16 g of inulin-type fructans (a mixture of oligofructose and inulin) and 16-g placebo (maltodextrin) for 6 weeks in randomised order. A 4-week washout separated the 6 weeks treatments. The faecal microbiota was analysed by high-throughput 16S rRNA amplicon sequencing and SCFA in faeces were analysed using vacuum distillation followed by gas chromatography. RESULTS: Treatment with inulin-type fructans induced moderate changes in the faecal microbiota composition (1.5%, p = 0.045). A bifidogenic effect was most prominent, with highest positive effect on operational taxonomic units (OTUs) of Bifidobacterium adolescentis, followed by OTUs of Bacteroides. Significantly higher faecal concentrations of total SCFA, acetic acid and propionic acid were detected after prebiotic consumption compared to placebo. The prebiotic fibre had no effects on the concentration of butyric acid or on the overall microbial diversity. CONCLUSION: Six weeks supplementation with inulin-type fructans had a significant bifidogenic effect and induced increased concentrations of faecal SCFA, without changing faecal microbial diversity. Our findings suggest a moderate potential of inulin-type fructans to improve gut microbiota composition and to increase microbial fermentation in type 2 diabetes. TRIAL REGISTRATION: The trial is registered at clinicaltrials.gov (NCT02569684).

Changes in Faecal Short-Chain Fatty Acids after Weight-Loss Interventions in Subjects with Morbid Obesity.

The gut microbiota and their metabolites, e.g., short-chain fatty acids (SCFA), are associated with obesity. The primary aims were to study faecal SCFA levels and the changes in SCFA levels after weight-loss interventions in subjects with obesity, and secondarily, to study factors associated with the faecal SCFA levels. In total, 90 subjects (men / women: 15/75) with a mean age of 44.4 (SD 8.4) years, BMI 41.7 (SD 3.7) kg/m2 and morbid obesity (BMI > 40 or > 35 kg/m2 with obesity-related complications) were included. Faecal SCFA and other variables were measured at inclusion and after a six-month conservative weight-loss intervention followed by bariatric surgery (RouxenY gastric bypass or gastric sleeve). Six months after surgery, the total amount of SCFA was reduced, the total and relative amounts of the main straight SCFA (acetic-, propionic-, and butyric- acids) were reduced, and the total and relative amounts of branched SCFA (isobutyric-, isovaleric-, and isocaproic- acids) were increased. The changes indicate a shift toward a proteolytic fermentation pattern with unfavorable health effects. The amount of SCFA was associated with the diet but not with metabolic markers or makers of the faecal microbiota composition. Dietary interventions could counteract the unfavorable effects.