Worldwide population prevalence and impact of sub-diagnostic gastrointestinal symptoms.

BACKGROUND: The Rome Foundation Global Epidemiology Study (RFGES) found that 40.3% of adults in 26 internet-surveyed countries met Rome IV criteria for disorders of gut-brain interaction (DGBI). However, additional people not meeting DGBI criteria may also be burdened by frequent gastrointestinal symptoms. AIMS: To explore the prevalence and demographic distribution of sub-diagnostic gastrointestinal symptoms, and the hypothesised associated effects on quality of life (QoL), life functioning and healthcare needs. METHODS: We analysed data from the RFGES survey, which included the Rome IV diagnostic questionnaire and QoL, psychological, work productivity and healthcare questions. RESULTS: Of the 50,033 people without a history of organic gastrointestinal disorders, 25.3% classified in the sub-diagnostic group (no DGBI but one or more frequent gastrointestinal symptoms), 41.4% had DGBI and 33.4% had no frequent gastrointestinal symptoms (non-GI group). Sub-diagnostic prevalence in different world regions ranged from 22.2% (North America) to 30.5% (Middle East), was slightly higher among males than females and decreased with age. The sub-diagnostic group was intermediate between the non-GI and DGBI groups, and significantly different from both of them on QoL, anxiety, depression, somatisation, healthcare utilisation and life and work impairment. CONCLUSIONS: One in four adults without organic gastrointestinal disorders or DGBI report frequent gastrointestinal symptoms. This sub-diagnostic group has reduced QoL, greater psychological and non-GI bodily symptoms, impaired work productivity and life activities and greater healthcare use compared to non-GI individuals. This suggests that many in this sub-diagnostic group might benefit from healthcare services or symptom self-management advice.

A poor diet quality is associated with more gas-related symptoms and a decreased quality of life in French adults.

This study evaluated the association between dietary patterns, Gas-Related Symptoms (GRS) and their impact on quality of life (QoL) in a representative sample (n=936) of the French adult population. During the 2018-2019 "Comportements et Consommations Alimentaires en France" (CCAF) survey (Behaviors and Food Consumption in France), online evaluation of GRS in adult participants was performed using the validated Intestinal Gas Questionnaire (IGQ), which captures the perception of GRS and their impact on QoL via 6 symptom dimensions scores (range 0-100; 100=worse) and a global score (mean of the sum of the 6 symptom dimensions scores). Socio-demographics, lifestyle parameters and dietary habits (7-day e-food diary) were also collected online. Quality of diet was determined using the NRF9.3 score (range 0-900; 900=best). Univariate and multivariate linear regression models were applied to identify factors associated with IGQ global score. K-means was used to identify clusters of subjects based on their dietary records. Data from 936 adults who completed both the IGQ and the food diary showed a mean (SD) IGQ global score of 11.9 (11.2). Younger age and female gender were associated with a higher IGQ global score. Only 7% of subjects reported no symptom at all and nearly 30% of study participants reported a high impact of GRS on their QoL. Two dietary clusters were identified: cluster1, characterized by a higher consumption of fruits and vegetables, lower sugars intake and higher NRF9.3 score and cluster 2, characterized by higher intake of sugars, lower intake in dietary fibers and lower NRF9.3 score. The IGQ global score was lower in cluster1 and higher in cluster2 vs. the total sample average (p<0.001). Prevalence of GRS in the French adult population is high and is associated with impaired QoL and dietary patterns. A change in food habits towards healthier patterns could help reducing the burden of GRS.

Attitudes and Expectations of Clinical Research Participants Toward Digital Health and Mobile Dietary Assessment Tools: Cross-Sectional Survey Study.

Background: The adoption of health technologies is key to empower research participants and collect quality data. However, the acceptance of health technologies is usually evaluated in patients or healthcare practitioners, but not in clinical research participants. Methods: A 27-item online questionnaire was provided to the 11,695 members of a nutrition clinical research participant database from the Nantes area (France), to assess (1) participants' social and demography parameters, (2) equipment and usage of health apps and devices, (3) expectations in research setting and (4) opinion about the future of clinical research. Each item was described using frequency and percentage overall and by age classes. A global proportion comparison was performed using chi-square or Fisher-exact tests. Results: A total of 1529 respondents (81.0% women, 19.0% men) completed the survey. Main uses of health apps included physical activity tracking (54.7%, age-related group difference, p < 0.001) and food quality assessment (45.7%, unrelated to age groups). Overall, 20.4% of respondents declared owning a connected wristband or watch. Most participants (93.8%) expected the use of connected devices in research. However, protection of personal data (37.5%), reliability (35.5%) and skilled use of devices (28.5%) were perceived as the main barriers. Most participants (93.3%) would agree to track their food intake using a mobile app, and 80.5% would complete it for at least a week while taking part in a clinical study. Only 13.2% would devote more than 10 min per meal to such record. A majority (60.4%) of respondents would accept to share their social media posts in an anonymous way and most (82.2%) of them would accept to interact with a chatbot for research purposes. Conclusions: Our cross-sectional study suggests that clinical study participants are enthusiastic about all forms of digital health technologies and participant-centered studies but remain concerned about the use of personal data. Repeated assessments are suggested to evaluate the research participant's interest in technologies following the increase in use and demand for innovative health services during the pandemic of COVID-19.

Gut microbiota and fermentation-derived branched chain hydroxy acids mediate health benefits of yogurt consumption in obese mice.

Meta-analyses suggest that yogurt consumption reduces type 2 diabetes incidence in humans, but the molecular basis of these observations remains unknown. Here we show that dietary yogurt intake preserves whole-body glucose homeostasis and prevents hepatic insulin resistance and liver steatosis in a dietary mouse model of obesity-linked type 2 diabetes. Fecal microbiota transplantation studies reveal that these effects are partly linked to the gut microbiota. We further show that yogurt intake impacts the hepatic metabolome, notably maintaining the levels of branched chain hydroxy acids (BCHA) which correlate with improved metabolic parameters. These metabolites are generated upon milk fermentation and concentrated in yogurt. Remarkably, diet-induced obesity reduces plasma and tissue BCHA levels, and this is partly prevented by dietary yogurt intake. We further show that BCHA improve insulin action on glucose metabolism in liver and muscle cells, identifying BCHA as cell-autonomous metabolic regulators and potential mediators of yogurt's health effects.

A Randomised, Controlled Trial: Effect of a Multi-Strain Fermented Milk on the Gut Microbiota Recovery after Helicobacter pylori Therapy.

Helicobacter pylori (Hp) eradication therapy alters gut microbiota, provoking gastrointestinal (GI) symptoms that could be improved by probiotics. The study aim was to assess the effect in Hp patients of a Test fermented milk containing yogurt and Lacticaseibacillus (L. paracasei CNCM I-1518 and I-3689, L. rhamnosus CNCM I-3690) strains on antibiotic associated diarrhea (AAD) (primary aim), GI-symptoms, gut microbiota, and metabolites. A randomised, double-blind, controlled trial was performed on 136 adults under 14-day Hp treatment, receiving the Test or Control product for 28 days. AAD and GI-symptoms were reported and feces analysed for relative and quantitative gut microbiome composition, short chain fatty acids (SCFA), and calprotectin concentrations, and viability of ingested strains. No effect of Test product was observed on AAD or GI-symptoms. Hp treatment induced a significant alteration in bacterial and fungal composition, a decrease of bacterial count and alpha-diversity, an increase of Candida and calprotectin, and a decrease of SCFA concentrations. Following Hp treatment, in the Test as compared to Control group, intra-subject beta-diversity distance from baseline was lower (padj = 0.02), some Enterobacteriaceae, including Escherichia-Shigella (padj = 0.0082) and Klebsiella (padj = 0.013), were less abundant, and concentrations of major SCFA (p = 0.035) and valerate (p = 0.045) were higher. Viable Lacticaseibacillus strains were detected during product consumption in feces. Results suggest that, in patients under Hp treatment, the consumption of a multi-strain fermented milk can induce a modest but significant faster recovery of the microbiota composition (beta-diversity) and of SCFA production and limit the increase of potentially pathogenic bacteria.

Safety and functional enrichment of gut microbiome in healthy subjects consuming a multi-strain fermented milk product: a randomised controlled trial.

Many clinical studies have evaluated the effect of probiotics, but only a few have assessed their dose effects on gut microbiota and host. We conducted a randomized, double-blind, controlled intervention clinical trial to assess the safety (primary endpoint) of and gut microbiota response (secondary endpoint) to the daily ingestion for 4 weeks of two doses (1 or 3 bottles/day) of a fermented milk product (Test) in 96 healthy adults. The Test product is a multi-strain fermented milk product, combining yogurt strains and probiotic candidate strains Lactobacillus paracasei subsp. paracasei CNCM I-1518 and CNCM I-3689 and Lactobacillus rhamnosus CNCM I-3690. We assessed the safety of the Test product on the following parameters: adverse events, vital signs, hematological and metabolic profile, hepatic, kidney or thyroid function, inflammatory markers, bowel habits and digestive symptoms. We explored the longitudinal gut microbiota response to product consumption and dose, by 16S rRNA gene sequencing and functional contribution by shotgun metagenomics. Safety results did not show any significant difference between the Test and Control products whatever the parameters assessed, at the two doses ingested daily over a 4-week-period. Probiotic candidate strains were detected only during consumption period, and at a significantly higher level for the three strains in subjects who consumed 3 products bottles/day. The global structure of the gut microbiota as assessed by alpha and beta-diversity, was not altered by consumption of the product for four weeks. A zero-inflated beta regression model with random effects (ZIBR) identified a few bacterial genera with differential responses to test product consumption dose compared to control. Shotgun metagenomics analysis revealed a functional contribution to the gut microbiome of probiotic candidates.

Differential Responses of Blood Essential Amino Acid Levels Following Ingestion of High-Quality Plant-Based Protein Blends Compared to Whey Protein-A Double-Blind Randomized, Cross-Over, Clinical Trial.

This study assessed the bio-equivalence of high-quality, plant-based protein blends versus Whey Protein Isolate (WPI) in healthy, resistance-trained men. The primary endpoint was incremental area under the curve (iAUC) of blood essential Amino Acids (eAAs) 4 hours after consumption of each product. Maximum concentration (Cmax) and time to maximum concentration (Tmax) of blood leucine were secondary outcomes. Subjects (n = 18) consumed three plant-based protein blends and WPI (control). An analysis of Variance model was used to assess for bio-equivalence of total sum of blood eAA concentrations. The total blood eAA iAUC ratios of the three blends were [90% CI]: #1: 0.66 [0.58-0.76]; #2: 0.71 [0.62-0.82]; #3: 0.60 [0.52-0.69], not completely within the pre-defined equivalence range [0.80-1.25], indicative of 30-40% lower iAUC versus WPI. Leucine Cmax of the three blends was not equivalent to WPI, #1: 0.70 [0.67-0.73]; #2: 0.72 [0.68-0.75]; #3: 0.65 [0.62-0.68], indicative of a 28-35% lower response. Leucine Tmax for two blends were similar to WPI (#1: 0.94 [0.73-1.18]; #2: 1.56 [1.28-1.92]; #3: 1.19 [0.95-1.48]). The plant-based protein blends were not bio-equivalent. However, blood leucine kinetic data across the blends approximately doubled from fasting concentrations, whereas blood Tmax data across two blends were similar to WPI. This suggests evidence of rapid hyperleucinemia, which correlates with a protein's anabolic potential.

Consumption of a Fermented Milk Product Containing Bifidobacterium lactis CNCM I-2494 in Women Complaining of Minor Digestive Symptoms: Rapid Response Which Is Independent of Dietary Fibre Intake or Physical Activity.

Background. Minor digestive symptoms are common and dietary approaches such as probiotic administration or fibre and fermentable carbohydrate intake adjustments are often recommended. A Fermented Milk Product (FMP) containing Bifidobacterium animalis subsp. lactis CNCM I-2494 and lactic acid bacteria has been shown to improve digestive symptoms after 4 weeks of consumption, but the speed of onset of this effect and its dependence on fibre intake or physical activity is unknown. To answer these questions, data from two previously published trials on FMP for minor digestive symptoms were combined. Methods. In total, 538 participants provided weekly assessments of bloating, abdominal pain/discomfort, flatulence, borborygmi/rumbling stomach from which a composite score was calculated. At baseline in one study (n = 336), dietary fibre consumption was recorded and physical activity classified as high, moderate or low. The speed of the FMP's effect was assessed by a repeated measure analysis of variance measuring the change from baseline for the composite score of digestive symptoms. Results. FMP consumption resulted in a significant decrease in the composite score of symptoms after only 2 weeks in both studies and the pooled data at week 1 (-0.35 [-0.69, 0.00]; p = 0.05), week 2 (-0.66 [-1.04, -0.27]; p < 0.001), week 3 (-0.49 [-0.89, -0.10]; p = 0.01) and week 4 (-0.46 [-0.88, -0.04]; p = 0.03). The interactions fibre intake-by-product group, physical activity-by-product group and time-by-product group were not statistically significant. Conclusion. FMP consumption leads to a rapid improvement in symptoms which is likely to encourage adherence to this dietary intervention. This effect is independent of dietary fibre and physical activity.

Brain natriuretic peptide usefulness in very elderly dyspnoeic patients: the BED study.

AIMS: To evaluate the interest of brain natriuretic peptide (BNP) for heart failure (HF) diagnosis in very old patients. METHODS AND RESULTS: A total of 383 patients aged 80 years or older, hospitalized in geriatrics care for dyspnoea, had a BNP measurement at the acute phase. Independent cardiologists blinded to BNP values classified the patients into cardiac vs. respiratory aetiology according to the European Society of Cardiology guidelines. Mean (SD) age was 88.5 (5.4) years, 66% (n = 254) of patients were women, 62% (n = 238) had cardiac dyspnoea and 38% (n = 145) had respiratory dyspnoea. The BNP levels were significantly higher in the cardiac group (median = 385.5 ng/L, interquartile range = 174.0-842.0) than in the respiratory group (median = 172.0 ng/L, interquartile range = 70.8-428.0; P < 0.001). On its own, BNP showed poor discriminative ability [area under the curve (AUC) = 0.68; 95% confidence interval (CI) 0.62-0.73] for the diagnostic. In multivariate analysis, BNP remained independently associated with the cardiac aetiology after full-adjustment (odds ratio 1 log increase = 1.87; 95% CI 1.28-2.74), but did not improve the discrimination between the cardiac and the respiratory aetiologies (ΔAUC = 0.013, P = 0.16). In addition, although adding BNP to the other predictive covariates yielded a significant continuous NRI of 57.8% (95% CI 31.2-83.5%), the mean changes in individual predicted probabilities were too low (<3%) to be clinically relevant. CONCLUSION: In this population of very old patients with acute dyspnoea, despite being independently associated with the cardiac aetiology, BNP was not useful for better discriminating cardiac vs. respiratory origin.

Plasmatic presepsin (sCD14-ST) concentrations in acute pyelonephritis in adult patients.

INTRODUCTION: Presepsin (sCD14-ST) is an emerging biomarker for infection. We hypothesized that presepsin could specifically increase during acute pyelonephritis and correlate with severity. METHODS: We compared presepsin values in patients with acute pyelonephritis and controls, and we assessed its capacity to predict bacteraemia and admission in patients. RESULTS: In 312 patients with acute pyelonephritis (median age 33years), presepsin concentrations were higher than in controls (476 vs 200ng/L, p<0.001). ROC curve indicated an AUC at 0.90 [for presepsin (vs. 0.99 and 0.98 for CRP and PCT, respectively; p<0.05) and an optimal threshold at 340ng/L (74% sensitivity, 94% specificity). Presepsin concentrations increased in acute pyelonephritis patients with bacteraemia (614 vs. 461ng/L, p,=0.001) and in those requiring admission (614ng/L vs. 320ng/L, p<0.001). Performance of presepsin to predict bacteraemia [AUC=0.63, 95%CI: 0.55-0.72] was similar to CRP (AUC=0.64, p=0.87) and less accurate than PCT (AUC=0.78, p<0.001). AUC for presepsin to detect the need for admission was 0.67, and comparable to CRP (p=0.26) and PCT (p=0.18). CONCLUSION: Presepsin is a valuable biomarker to detect patients with acute pyelonephritis. However, it presents mild performance to predict bacteraemia and the need for admission, and offers no advantage as compared to CRP and PCT.