Characterization of luminal contents from the fasted human proximal colon.

To treat colonic diseases more effectively, improved therapies are urgently needed. In this respect, delivering drugs locally to the colon is a key strategy to achieve higher local drug concentrations while minimizing systemic side effects. Understanding the luminal environment is crucial to efficiently develop such targeted therapies and to predict drug disposition in the colon. In this clinical study, we collected colonic contents from an undisturbed fasted proximal colon via colonoscopy and characterized their composition with regard to drug disposition. Colonic pH, osmolality, protein content, bile salts, lipids, phospholipids and short-chain fatty acids were investigated in 10 healthy volunteers (8 male and 2 female, age 19-25). The unique environment of the proximal colon was reflected in the composition of the sampled luminal fluids and the effect of the microbiota could be observed on the pH (median 6.55), the composition of bile salts (majority deconjugated and secondary), and the abundance of short-chain fatty acids. At the same time, an increase in phospholipid concentration, osmolality and total protein content compared to reported ileal values was seen, likely resulting from desiccation. Lipids could only be found in low quantities and mainly in the form of cholesterol and free fatty acids, showing almost complete digestion and absorption by the time luminal contents reach the colon. All characteristics also displayed the considerable intersubject variability found in different regions of the gastrointestinal tract. This study contributes to an improved understanding of the luminal conditions in the proximal colon and facilitates the development of new predictive tools to study colonic drug absorption.

The Leuven Prolonged Acute Stress Test (L-PAST): A novel paradigm to induce a subjective and glucocorticoid stress response for at least ninety minutes.

Laboratory stress tests typically administer stress acutely, ranging from 3 to 15 minutes. However, everyday stressors usually last longer than ten minutes (e.g., examination stressors, work stressors, and social stressors. Moreover, in some studies, it may be relevant to induce stress for a longer period to affect certain psychological or physiological parameters. To this end, we developed a novel stress test that intends to induce psychosocial stress for 90 minutes. The Leuven Prolonged Acute Stress Test (L-PAST) combines physical (hand immersion in cold water), cognitive (mental arithmetic), and psychosocial (social evaluation and feelings of failure) stress elements of two well-known laboratory stress tests, the Maastricht Acute Stress Test (MAST) and the Montreal Imaging Stress Test (MIST). Fifty healthy women were subjected to both the L-PAST and a sham (control) test in a randomized and counterbalanced manner. The stress response was determined by salivary cortisol measurements and assessment of subjective stress ratings at regular time points during the time preceding the stress period (5 min), the stress period (90 min), and the recovery period (35 min). Cognitive reactivity to failure and subjective pain levels were also assessed at various time points. The childhood trauma questionnaire (CTQ) and the perceived stress scale (PSS) were administered prior to the testing phase. As expected, linear mixed models revealed that the stress response was significantly higher during the L-PAST as indicated by a significant time point by condition interaction effect for both the cortisol response (F(10,450)=12.21, p < 0.0001, ηp2=0.11) and the subjective stress response (F(13,637)=13.98, p < 0.0001, ηp2 = 0.12). Moreover, there was a significant time point by condition interaction effect for cognitive reactivity to failure (F(13,637) = 7.97, p < 0.0001, ηp2 = 0.07) and subjective pain (F(13,637) = 38.52, p < 0.0001, ηp2 = 0.27), indicating that the levels were higher during the L-PAST at most stress induction time points. Lastly, higher CTQ scores were associated with higher subjective pain levels during the L-PAST (F(1,44)=6.05, p = 0.02). Collectively, our results confirm the efficacy of the L-PAST in inducing a prolonged subjective as well as cortisol stress response.

Added Value of 13C Analysis in Breath Tests in H2-Negative Subjects to Diagnose Lactose Malabsorption: A Proof of Concept Study.

INTRODUCTION: Diagnosing lactose malabsorption is usually based on hydrogen excretion in breath after a lactose challenge. However, a proportion of subjects with lactose malabsorption will not present a rise in hydrogen. Measuring excretion of methane or stable isotope labeled 13CO2 after ingestion of 13C-lactose has been proposed to mitigate this problem. OBJECTIVE: The aim of the study was to assess the performance of measuring methane and 13CO2 in individuals with normal hydrogen excretion compared to a genetic lactase non-persistence test. METHODS: Individuals referred for lactose breath testing and healthy controls were included. Participants received 13C-enriched lactose, performed breath testing, and underwent genotyping for a marker of lactase non-persistence (13910C*T). Using genotype as gold standard, the performance of measuring methane and 13CO2 excretion was assessed. RESULTS: 151 subjects participated in the study, 50 of which presented a lactase non-persistent genotype. Of these, 72% were correctly diagnosed through hydrogen excretion of ≥ 20 ppm above baseline. In subjects with normal hydrogen excretion, cumulative 13C excretion had an area under the curve (AUC) of the receiver operating characteristics (ROC) curve of 0.852. Sensitivity was 93% and specificity was 51% for the current cutoff of 14.5%. The optimal cutoff was 12.65% (sensitivity 93%, specificity 70%). The ROC curve of peak methane had an AUC of 0.542 (sensitivity of 14%, specificity of 91% for cutoff ≥ 10 ppm). CONCLUSIONS: In individuals with genetically demonstrated lactase non-persistence and negative hydrogen breath test, the use of 13C-lactose with measurement of 13CO2 excretion and hydrogen is a well-performing test to detect the lactose malabsorption and performs better than methane in our cohort.

Colonic butyrate administration modulates fear memory but not the acute stress response in men: A randomized, triple-blind, placebo-controlled trial.

Short-chain fatty acids (SCFAs) are produced in the colon following bacterial fermentation of dietary fiber and are important microbiota-gut-brain messengers. However, their mechanistic role in modulating psychobiological processes that underlie the development of stress- and anxiety-related disorders is scarcely studied in humans. We have previously shown that colonic administration of a SCFA mixture (acetate, propionate, butyrate) lowers the cortisol response to stress in healthy participants, but does not impact fear conditioning and extinction. To disentangle the effects of the three main SCFAs, we examined whether butyrate alone would similarly modulate these psychobiological responses in a randomized, triple-blind, placebo-controlled intervention study in 71 healthy male participants (Mage = 25.2, MBMI = 22.7 [n = 35 butyrate group, n = 36 placebo group]). Colon-delivery capsules with pH-dependent coating were used to administer 5.28 g of butyrate or placebo daily for one week. Butyrate administration significantly increased serum butyrate concentrations without modulating serum acetate or propionate, nor fecal SCFAs. Butyrate administration also significantly modulated fear memory at the subjective but not physiological levels. Contrary to expectations, no changes in subjective nor neuroendocrine responses to acute stress were evident between the treatment groups from pre- to post-intervention. We conclude that colonic butyrate administration alone is not sufficient to modulate psychobiological stress responses, unlike administration of a SCFA mixture. The influence of colonic and systemic butyrate on fear memory and the persistence of fear extinction should be further systematically investigated in future studies.

The role of short-chain fatty acids (SCFAs) in regulating stress responses, eating behavior, and nutritional state in anorexia nervosa: protocol for a randomized controlled trial.

OBJECTIVE: This protocol proposes investigating the effects of short-chain fatty acids (SCFAs)-namely acetate, propionate, and butyrate-as mediators of microbiota-gut-brain interactions on the acute stress response, eating behavior, and nutritional state in malnourished patients with anorexia nervosa (AN). SCFAs are produced by bacterial fermentation of dietary fiber in the gut and have recently been proposed as crucial mediators of the gut microbiota's effects on the host. Emerging evidence suggests that SCFAs impact human psychobiology through endocrine, neural, and immune pathways and may regulate stress responses and eating behavior. METHOD: We will conduct a randomized, triple-blind, placebo-controlled trial in 92 patients with AN. Patients will receive either a placebo or a mixture of SCFAs (acetate propionate, butyrate) using pH-dependent colon-delivery capsules for six weeks. This clinical trial is an add-on to the standard inpatient psychotherapeutic program focusing on nutritional rehabilitation. HYPOTHESES: We hypothesize that colonic SCFAs delivery will modulate neuroendocrine, cardiovascular, and subjective responses to an acute laboratory psychosocial stress task. As secondary outcome measures, we will assess alterations in restrictive eating behavior and nutritional status, as reflected by changes in body mass index. Additionally, we will explore changes in microbiota composition, gastrointestinal symptoms, eating disorder psychopathology, and related comorbidities. DISCUSSION: The findings of this study would enhance our understanding of how gut microbiota-affiliated metabolites, particularly SCFAs, impact the stress response and eating behavior of individuals with AN. It has the potential to provide essential insights into the complex interplay between the gut, stress system, and eating behavior and facilitate new therapeutic targets for stress-related psychiatric disorders. This protocol is prospectively registered with ClinicalTrials.gov, with trial registration number NCT06064201.

Psychosocial stress-induced intestinal permeability in healthy humans: What is the evidence?

An impaired intestinal barrier function can be detrimental to the host as it may allow the translocation of luminal antigens and toxins into the subepithelial tissue and bloodstream. In turn, this may cause local and systemic immune responses and lead to the development of pathologies. In vitro and animal studies strongly suggest that psychosocial stress is one of the factors that can increase intestinal permeability via mast-cell dependent mechanisms. Remarkably, studies have not been able to yield unequivocal evidence that such relation between stress and intestinal permeability also exists in (healthy) humans. In the current Review, we discuss the mechanisms that are involved in stress-induced intestinal permeability changes and postulate factors that influence these alterations and that may explain the translational difficulties from in vitro and animal to human studies. As human research differs highly from animal research in the extent to which stress can be applied and intestinal permeability can be measured, it remains difficult to draw conclusions about the presence of a relation between stress and intestinal permeability in (healthy) humans. Future studies should bear in mind these difficulties, and more research into in vivo methods to assess intestinal permeability are warranted.

Systematic optimization of fermentation conditions for in vitro fermentations with fecal inocula.

In vitro fermentation strategies with fecal inocula are considered cost-effective methods to gain mechanistic insights into fecal microbiota community dynamics. However, all in vitro approaches have their limitations due to inherent differences with respect to the in vivo situation mimicked, introducing possible biases into the results obtained. Here, we aimed to systematically optimize in vitro fermentation conditions to minimize drift from the initial inoculum, limit growth of opportunistic colonizers, and maximize the effect of added fiber products (here pectin) when compared to basal medium fermentations. We evaluated the impact of varying starting cell density and medium nutrient concentration on these three outcomes, as well as the effect of inoculation with fresh vs. stored fecal samples. By combining GC-MS metabolite profiling and 16 s rRNA gene-based amplicon sequencing, we established that starting cell densities below 1010 cells/ml opened up growth opportunities for members the Enterobacteriaceae family. This effect was exacerbated when using fecal samples that were stored frozen at -80°C. Overgrowth of Enterobacteriaceae resulted in lowered alpha-diversity and larger community drift, possibly confounding results obtained from fermentations in such conditions. Higher medium nutrient concentrations were identified as an additional factor contributing to inoculum community preservation, although the use of a less nutrient dense medium increased the impact of fiber product addition on the obtained metabolite profiles. Overall, our microbiome observations indicated that starting cell densities of 1010 cells/ml limited opportunities for exponential growth, suppressing in vitro community biases, whilst metabolome incubations should preferably be carried out in a diluted medium to maximize the impact of fermentable substrates.

Bifidobacterium longum subsp. longum Reduces Perceived Psychological Stress in Healthy Adults: An Exploratory Clinical Trial.

Emerging science shows that probiotic intake may impact stress and mental health. We investigated the effect of a 6-week intervention with Bifidobacterium longum (BL) NCC3001 (1 × 1010 CFU/daily) on stress-related psychological and physiological parameters in 45 healthy adults with mild-to-moderate stress using a randomized, placebo-controlled, two-arm, parallel, double-blind design. The main results showed that supplementation with the probiotic significantly reduced the perceived stress and improved the subjective sleep quality score compared to placebo. Comparing the two groups, momentary subjective assessments concomitant to the Maastricht Acute Stress Test revealed a lower amount of pain experience in the probiotic group and a higher amount of relief at the end of the procedure in the placebo group, reflected by higher scores in the positive affect state. The awakening of the salivary cortisol response was not affected by the intervention, yet the reduction observed in the salivary cortisol stress response post-intervention was higher in the placebo group than the probiotic group. Multivariate analysis further indicated that a reduction in perceived stress correlated with a reduction in anxiety, in depression, and in the cortisol awakening response after the 6-week intervention. This exploratory trial provides promising insights into BL NCC3001 to reduce perceived stress in a healthy population and supports the potential of nutritional solutions including probiotics to improve mental health.

Promotion of starch retrogradation by enzymatic elongation of amylopectin chains does not reduce glycemic responses: a randomized cross-over clinical trial.

The molecular structure of amylopectin (AP) governs the propensity of its chains to re-associate into crystalline arrangements after starch gelatinization. Amylose (AM) crystallization and AP re-crystallization (i.e. retrogradation) decrease starch digestibility. The aim of this work was to enzymatically elongate AP chains using an amylomaltase (AMM, i.e. 4-α-glucanotransferase) from Thermus thermophilus to promote AP retrogradation and to investigate the impact thereof on in vivo glycemic responses in healthy subjects. Participants (n = 32) consumed two oatmeal porridges (containing 22.5 g available carbohydrates) prepared with or without the enzymatic modification and stored at 4 °C for 24 h. Finger-prick blood samples were taken fasting and at intervals during 3 h following test-meal consumption. The incremental area under the curve (iAUC0-180) was determined. The AMM was very effective at elongating the AP chains at the expense of AM, resulting in increased retrogradation capacity upon storage at low temperature. Nevertheless, postprandial glycemic responses were not different after consumption of either the AMM modified oatmeal porridge or its unmodified counterpart (iAUC0-180 = 73 ± 30 vs. 82 ± 43 mmol min L-1, respectively; p = 0.17). Unexpectedly, promoting starch retrogradation by selectively modifying its molecular structure did not result in reduced glycemic responses, challenging the notion that starch retrogradation negatively impacts glycemic responses in vivo.

Perspective: Assessing Tolerance to Nondigestible Carbohydrate Consumption.

Human intestinal enzymes do not hydrolyze nondigestible carbohydrates (NDCs), and thus, they are not digested and absorbed in the small intestine. Instead, NDCs are partially to completely fermented by the intestinal microbiota. Select NDCs are associated with health benefits such as laxation and lowering of blood cholesterol and glucose. NDCs provide functional attributes to processed foods, including sugar or fat replacers, thickening agents, and bulking agents. Additionally, NDCs are incorporated into processed foods to increase their fiber content. Although consumption of NDCs can benefit health and contribute functional characteristics to foods, they can cause gastrointestinal symptoms, such as flatulence and bloating. As gastrointestinal symptoms negatively affect consumer well-being and their acceptance of foods containing NDC ingredients, it is crucial to consider tolerance when designing food products and testing their physiological health benefits in clinical trials. This perspective provides recommendations for the approach to assess gastrointestinal tolerance to NDCs, with a focus on study design, population criteria, intervention, comparator, and outcome. Special issues related to studies in children and implications for stakeholders are also discussed. It is recommended that the evaluation of gastrointestinal tolerance to NDCs be conducted in randomized, blinded, controlled crossover studies using standard gastrointestinal questionnaires, with attention to study participant background diets, health status, lifestyle, and medications.

Extruded Wheat Bran Consumption Increases Serum Short-Chain Fatty Acids but Does Not Modulate Psychobiological Functions in Healthy Men: A Randomized, Placebo-Controlled Trial.

Background: Incorporation of wheat bran (WB) into food products increases intake of dietary fiber, which has been associated with improved mood and cognition and a lower risk for psychiatric disorders such as depression, with short-chain fatty acids (SCFAs) as candidate mediators of these effects. Modifying WB using extrusion cooking increases SCFA production in vitro relative to unmodified WB. Objective: The aim of this study was to evaluate the effects of extruded WB on psychobiological functioning and the mediating role of SCFAs. Methods: In a randomized, triple-blind, placebo-controlled trial, 69 healthy male participants consumed 55 g of breakfast cereal containing either extruded WB or placebo daily for 28 days. At pre- and post-intervention visits, the cortisol response to experimentally induced stress was measured as a primary outcome. In addition, serum SCFAs and brain-derived neurotrophic factors were quantified as potential mediators. Secondary psychobiological outcomes included subjective stress responses, responses to experimentally induced fear, cortisol awakening response, heart rate variability, and retrospective subjective mood ratings. Intestinal permeability, fecal SCFAs, and stool consistency were measured as secondary biological outcomes. Results: Extruded WB increased serum acetate and butyrate (p < 0.05). None of the primary or secondary outcomes were affected by the intervention. Participants who consumed a placebo exhibited an increase in the percentage of fecal dry weight but did not report increased constipation. Despite these statistically significant effects, these changes were small in magnitude. Conclusions: Extruded WB consumption increased serum short-chain fatty acids but did not modulate psychobiological functions in healthy men. Effective modulation of psychobiological functions may require greater increases in SCFAs than those achieved following extruded WB consumption. Rather than attempting to induce health benefits with a single fiber-rich food, combinations of different fibers, particularly highly fermentable ones, might be needed to further increase SCFA production and uptake in the systemic circulation to observe an effect on psychobiological processes.

Gut microbiota transplantation drives the adoptive transfer of colonic genotype-phenotype characteristics between mice lacking catestatin and their wild type counterparts.

The gut microbiota is in continuous interaction with the intestinal mucosa via metabolic, neuro-immunological, and neuroendocrine pathways. Disruption in levels of antimicrobial peptides produced by the enteroendocrine cells, such as catestatin, has been associated with changes in the gut microbiota and imbalance in intestinal homeostasis. However, whether the changes in the gut microbiota have a causational role in intestinal dyshomeostasis has remained elusive. To this end, we performed reciprocal fecal microbial transplantation in wild-type mice and mice with a knockout in the catestatin coding region of the chromogranin-A gene (CST-KO mice). Combined microbiota phylogenetic profiling, RNA sequencing, and transmission electron microscopy were employed. Fecal microbiota transplantation from mice deficient in catestatin (CST-KO) to microbiota-depleted wild-type mice induced transcriptional and physiological features characteristic of a distorted colon in the recipient animals, including impairment in tight junctions, as well as an increased collagen area fraction indicating colonic fibrosis. In contrast, fecal microbiota transplantation from wild-type mice to microbiota-depleted CST-KO mice reduced collagen fibrotic area, restored disrupted tight junction morphology, and altered fatty acid metabolism in recipient CST-KO mice. This study provides a comprehensive overview of the murine metabolic- and immune-related cellular pathways and processes that are co-mediated by the fecal microbiota transplantation and supports a prominent role for the gut microbiota in the colonic distortion associated with the lack of catestatin in mice. Overall, the data show that the gut microbiota may play a causal role in the development of features of intestinal inflammation and metabolic disorders, known to be associated with altered levels of catestatin and may, thus, provide a tractable target in the treatment and prevention of these disorders.

Catestatin selects for colonization of antimicrobial-resistant gut bacterial communities.

The gut microbiota is in continuous interaction with the innermost layer of the gut, namely the epithelium. One of the various functions of the gut epithelium, is to keep the microbes at bay to avoid overstimulation of the underlying mucosa immune cells. To do so, the gut epithelia secrete a variety of antimicrobial peptides, such as chromogranin A (CgA) peptide catestatin (CST: hCgA352-372). As a defense mechanism, gut microbes have evolved antimicrobial resistance mechanisms to counteract the killing effect of the secreted peptides. To this end, we treated wild-type mice and CST knockout (CST-KO) mice (where only the 63 nucleotides encoding CST have been deleted) with CST for 15 consecutive days. CST treatment was associated with a shift in the diversity and composition of the microbiota in the CST-KO mice. This effect was less prominent in WT mice. Levels of the microbiota-produced short-chain fatty acids, in particular, butyrate and acetate were significantly increased in CST-treated CST-KO mice but not the WT group. Both CST-treated CST-KO and WT mice showed a significant increase in microbiota-harboring phosphoethanolamine transferase-encoding genes, which facilitate their antimicrobial resistance. Finally, we show that CST was degraded by Escherichia coli via an omptin-protease and that the abundance of this gene was significantly higher in metagenomic datasets collected from patients with Crohn's disease but not with ulcerative colitis. Overall, this study illustrates how the endogenous antimicrobial peptide, CST, shapes the microbiota composition in the gut and primes further research to uncover the role of bacterial resistance to CST in disease states such as inflammatory bowel disease.

Lactobacillus rhamnosus CNCM I-3690 decreases subjective academic stress in healthy adults: a randomized placebo-controlled trial.

Psychological stress negatively affects the intestinal barrier function in animals and humans. We aimed to study the effect of Lactobacillus rhamnosus CNCM I-3690 on intestinal permeability and stress-markers during public speech. Healthy students were randomized to L. rhamnosus-containing (test) or acidified (placebo) milk consumed twice daily for 4 weeks, with 46 subjects per treatment group. Small intestinal permeability was quantified by a 2 h urinary lactulose-mannitol ratio (LMR, primary outcome), fractional excretion of lactulose (FEL) and mannitol (FEM). Salivary cortisol, State-Trait Anxiety Inventory (STAI) and Perceived Stress scores (PSS) were collected. No between-treatment differences were found for LMR (p = .71), FEL or FEM. Within-treatment analyses showed similar LMR and FEL but a stress-induced increase of FEM with the placebo (p < .05) but not test product. Despite a similar increase in salivary cortisol, the stress-induced increase in STAI was significantly lower with the test product vs. placebo (p = .01). Moreover, a stress-preventative effect of the probiotic was found for PSS and more pronounced in subjects with high stress-induced cortisol (p = .01). While increased FEM was mediated by salivary cortisol levels, the effect of the test product on subjective stress was not mediated by changes in FEM. No serious adverse events occurred. In conclusion, we demonstrated that L. rhamnosus CNCM I-3690 prevented stress-induced hyperpermeability to mannitol. Subjective but not objective stress-markers were reduced with L. rhamnosus vs. placebo, suggesting anxiolytic effects, which were independent of barrier stabilization and attractive for the reduction of stress in both health and disease. Clinicaltrials.gov, number NCT03408691.

When the mind says one thing, but the HPA axis says another: Lack of coherence between subjective and neuroendocrine stress response trajectories in healthy men.

Psychological stress triggers the release of cortisol following the activation of the hypothalamic-pituitary-adrenal (HPA) axis and elicits concomitant subjective responses. Coherence among the stress response systems is theoretically expected, presumably to optimize the organism's response to environmental challenges, but has received little empirical support possibly due to the assumption of linear associations. The present study examined the associations between cortisol responses to the Maastricht Acute Stress Test (MAST) and concomitant subjective stress responses as well as mood states over the past weeks in 133 healthy men. Latent class growth analysis (LCGA) was applied on individual cortisol and subjective stress responses to identify homogeneous response trajectories within the larger heterogeneous population and enable testing non-linear relationships while retaining the temporal resolution of the stress responses. LCGA revealed four latent cortisol response classes, labeled as mild responders (n = 15), moderately-low responders (n = 46), moderately-high responders (n = 48), and hyper responders (n = 24). These latent classes were not associated with concomitant subjective stress responses. Similarly, the three distinct latent classes capturing the variability in subjective stress responses were also not associated with concomitant cortisol responses. Experiencing higher levels of stress over the previous weeks, however, increased the likelihood of exhibiting a hyper cortisol stress response profile. Positive and negative affective states, and anxious and depressive symptomology over the previous weeks were not associated with cortisol response trajectories. Contrary to previous findings supporting a quadratic association in healthy females, our results do not support the response coherence hypothesis in healthy males subjected to the MAST, but suggest that recent levels of perceived stress may influence the cortisol response to acute stress.

Reply to Erren et al. Chronodisruption: Origin, Roots, and Developments of an 18-Year-Old Concept. Comment on "Desmet et al. Time-Restricted Feeding in Mice Prevents the Disruption of the Peripheral Circadian Clocks and Its Metabolic Impact during Chronic Jetlag. Nutrients 2021, 13, 3846".

We would like to thank Erren et al. [...].

The impact of bariatric surgery on macronutrient malabsorption depends on the type of procedure.

Introduction: Bariatric surgery, currently the most effective treatment for morbidly obese patients, may induce macronutrient malabsorption depending on the type of procedure. Macronutrient malabsorption affects the supply of substrates to the colon, subsequent microbial fermentation and possibly colonic health. Methods: Using isotope technology, we quantified the extent of macronutrient and bile acid malabsorption and its impact on colonic protein fermentation in patients after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) and in controls. Participants consumed a single test meal (day 0) that contained intrinsically labeled (13C, 15N, and 2H) egg protein for quantification of protein digestion, malabsorption and fermentation, respectively, together with a transit marker and a marker for bile acid malabsorption. They collected breath samples up to 6 h and all urine and stool for 48 and 72 h, respectively. Food intake was registered from day -3 to day 2. Results: Malabsorption of fat, protein and carbohydrates differed between groups (p = 0.040; p = 0.046; and p = 0.003, respectively) and was slightly higher in RYGB but not in SG patients compared to controls. Protein fermentation was increased in both RYGB and SG patients compared to controls (p = 0.001) and was negatively correlated to 2H-recovery as a marker of transit (ρ = -0.47, p = 0.013). Conclusion: The limited macronutrient malabsorption likely does not affect the nutritional status of the patient. However, the higher protein fermentation may affect colonic health and warrants further investigation.

Time-Restricted Feeding in Mice Prevents the Disruption of the Peripheral Circadian Clocks and Its Metabolic Impact during Chronic Jetlag.

We used time-restricted feeding (TRF) to investigate whether microbial metabolites and the hunger hormone ghrelin can become the dominant entraining factor during chronic jetlag to prevent disruption of the master and peripheral clocks, in order to promote health. Therefore, hypothalamic clock gene and Agrp/Npy mRNA expression were measured in mice that were either chronically jetlagged and fed ad libitum, jetlagged and fed a TRF diet, or not jetlagged and fed a TRF diet. Fecal short-chain fatty acid (SCFA) concentrations, plasma ghrelin and corticosterone levels, and colonic clock gene mRNA expression were measured. Preventing the disruption of the food intake pattern during chronic jetlag using TRF restored the rhythmicity in hypothalamic clock gene mRNA expression of Reverbα but not of Arntl. TRF countered the changes in plasma ghrelin levels and in hypothalamic Npy mRNA expression induced by chronic jetlag, thereby reestablishing the food intake pattern. Increase in body mass induced by chronic jetlag was prevented. Alterations in diurnal fluctuations in fecal SCFAs during chronic jetlag were prevented thereby re-entraining the rhythmic expression of peripheral clock genes. In conclusion, TRF during chronodisruption re-entrains the rhythms in clock gene expression and signals from the gut that regulate food intake to normalize body homeostasis.

Structural factors governing starch digestion and glycemic responses and how they can be modified by enzymatic approaches: A review and a guide.

Starch is the most abundant glycemic carbohydrate in the human diet. Consumption of starch-rich food products that elicit high glycemic responses has been linked to the occurrence of noncommunicable diseases such as cardiovascular disease and diabetes mellitus type II. Understanding the structural features that govern starch digestibility is a prerequisite for developing strategies to mitigate any negative health implications it may have. Here, we review the aspects of the fine molecular structure that in native, gelatinized, and gelled/retrograded starch directly impact its digestibility and thus human health. We next provide an informed guidance for lowering its digestibility by using specific enzymes tailoring its molecular and three-dimensional supramolecular structure. We finally discuss in vivo studies of the glycemic responses to enzymatically modified starches and relevant food applications. Overall, structure-digestibility relationships provide opportunities for targeted modification of starch during food production and improving the nutritional profile of starchy foods.