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Exploration of differential responses to FODMAPs and gluten in people with irritable bowel syndrome- a double-blind randomized cross-over challenge study.
Nordin, E, Landberg, R, Hellström, PM, Brunius, C
Metabolomics : Official journal of the Metabolomic Society. 2024;20(2):21
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Irritable bowel syndrome (IBS) is a complex condition characterized by recurrent abdominal pain associated with abnormal bowel habits. Diet is considered a main cause of symptoms in IBS, and fermentable oligo-, di-, monosaccharides, and polyols (FODMAPs) are of major concern. The aim of this study was to unravel determinants of differential IBS responses to FODMAP and gluten provocation interventions from molecular data. This study was a randomised, double-blind, placebo-controlled three-way crossover study. Participants were randomised in blocks of 12 into the sequences CBA, ACB, and BAC (A=FODMAPs, B=Gluten, and C=Placebo). Results showed that despite a comprehensive set of methods applied to explore IBS responses, including both regression and classification, predictors of differential response could not be established. Authors concluded by encouraging the application of molecular subtyping methodologies in future studies due to the differential responses to treatment.
Abstract
INTRODUCTION There is large variation in response to diet in irritable bowel syndrome (IBS) and determinants for differential response are poorly understood. OBJECTIVES Our aim was to investigate differential clinical and molecular responses to provocation with fermentable oligo-, di-, monosaccharides, and polyols (FODMAPs) and gluten in individuals with IBS. METHODS Data were used from a crossover study with week-long interventions with either FODMAPs, gluten or placebo. The study also included a rapid provocation test. Molecular data consisted of fecal microbiota, short chain fatty acids, and untargeted plasma metabolomics. IBS symptoms were evaluated with the IBS severity scoring system. IBS symptoms were modelled against molecular and baseline questionnaire data, using Random Forest (RF; regression and clustering), Parallel Factor Analysis (PARAFAC), and univariate methods. RESULTS Regression and classification RF models were in general of low predictive power (Q2 ≤ 0.22, classification rate < 0.73). Out of 864 clustering models, only 2 had significant associations to clusters (0.69 < CR < 0.73, p < 0.05), but with no associations to baseline clinical measures. Similarly, PARAFAC revealed no clear association between metabolome data and IBS symptoms. CONCLUSION Differential IBS responses to FODMAPs or gluten exposures could not be explained from clinical and molecular data despite extensive exploration with different data analytical approaches. The trial is registered at www. CLINICALTRIALS gov as NCT03653689 31/08/2018.
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Effects of Spirulina supplementation in patients with ulcerative colitis: a double-blind, placebo-controlled randomized trial.
Moradi, S, Bagheri, R, Amirian, P, Zarpoosh, M, Cheraghloo, N, Wong, A, Zobeiri, M, Entezari, MH
BMC complementary medicine and therapies. 2024;24(1):109
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Ulcerative colitis (UC) is a form of inflammatory bowel disease, that may be caused by genetic variations in the gut microbiome, immune dysregulation, and environmental influences. Symptoms include diarrhoea, constipation, cramping, joint pain, bleeding, and anaemia. Inflammation is a direct driver of UC, which if controlled may be of benefit to the individual. Spirulina, which is a species of seaweed, has been shown to have anti-inflammatory properties and this randomised control trial aimed to determine the effects of its supplementation on 80 individuals with UC and associated health outcomes. The results showed that 8-weeks of Spirulina supplementation significantly increased antioxidant capacity compared to placebo. However, an assessment of quality of life and level of disease showed no improvements with Spirulina supplementation. It was concluded that Spirulina supplementation for 8-weeks improved antioxidant status, but it did not affect severity of disease or quality of life. This study could be used by healthcare professionals to understand that Spirulina supplementation for 8-weeks can improve inflammation. However, it would be interesting to see longer studies to determine if this would affect disease status if supplemented for a longer period of time.
Abstract
AIM: We conducted a randomized placebo-controlled trial to assess the efficacy of Spirulina (SP) supplementation on disease activity, health-related quality of life, antioxidant status, and serum pentraxin 3 (PTX-3) levels in patients with ulcerative colitis (UC). METHODS Eighty patients with UC were randomly assigned to consume either 1 g/day (two 500 mg capsules/day) of SP (n = 40) or control (n = 40) for 8 weeks. Dietary intakes, physical activity, disease activity, health-related quality of life, antioxidant status, erythrocyte sedimentation rate (ESR), and serum PTX-3 levels were assessed and compared between groups at baseline and post-intervention. RESULTS Seventy-three patients (91.3%) completed the trial. We observed increases in serum total antioxidant capacity levels in the SP supplementation group compared to the control group after 8 weeks of intervention (p ≤ 0.001). A within-group comparison indicated a trend towards a higher health-related quality of life score after 8 weeks of taking two different supplements, SP (p < 0.001) and PL (p = 0.012), respectively. However, there were no significant changes in participant's disease activity score in response to SP administration (p > 0.05). Similarly, changes in ESR and PTX-3 levels were comparable between groups post-intervention (p > 0.05). CONCLUSIONS SP improved antioxidant capacity status and health-related quality of life in patients with UC. Our findings suggest that SP supplementation may be effective as an adjuvant treatment for managing patients with UC. Larger trials with longer interventions periods are required to confirm our findings.
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Physical Training and Healthy Diet Improved Bowel Symptoms, Quality of Life, and Fatigue in Children With Inflammatory Bowel Disease.
Scheffers, LE, Vos, IK, Utens, EMWJ, Dieleman, GC, Walet, S, Escher, JC, van den Berg, LEM
Journal of pediatric gastroenterology and nutrition. 2023;77(2):214-221
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Inflammatory bowel disease (IBD), including Crohn disease and ulcerative colitis, are chronic inflammatory diseases of the gastrointestinal tract, characterised by periods of remission and relapse of symptoms. The aim of this study was to assess the effects of a tailored lifestyle intervention on physical fitness (maximal and submaximal exercise capacity, strength, and core stability), the patient-reported outcomes (quality of life, fatigue, and fear), clinical disease activity, and nutritional status. This study was a prospective single-centre randomised semi-crossover-controlled trial. Children were randomized into group A (start exercise) or group B (start control period). Results showed improved physical fitness, quality of life, and parent-reported fatigue. Additionally, a combination of lower clinical disease activity scores accompanied by fewer IBD symptoms suggests positive effects on intestinal inflammation. Authors concluded that based on the findings of their study, children and adolescents with IBD should be motivated and supported to acquire and maintain a healthy lifestyle.
Expert Review
Conflicts of interest:
None
Take Home Message:
- IBD is a chronic inflammatory disease of the gastrointestinal tract, characterised by periods of abdominal pain, severe diarrhoea, and fatigue
- This clinical trial suggests that a 12-week program of physical training plus personalised healthy dietary advice may improve physical fitness, quality of life, and fatigue in children with IBD.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
A randomised semi-crossover controlled trial was conducted to investigate the impact of a 12-week lifestyle program (3 physical training sessions per week plus personalised healthy dietary advice) in children with Inflammatory Bowel Disease (IBD).
Method
- Sixteen children with a median age of 15 [IQR: 12–16]) that were diagnosed with IBD (CD, UC, or IBD-unclassified) were randomized to group A (start exercise) or group B (start control period). Group A started the intervention immediately after the first assessment and did not have a control period. Group B started after a control period (this was planned to last for 6 weeks but due to the COVID-19 lockdown extended to 6 months)
- The lifestyle intervention lasted 12 weeks and consisted of 3 physiotherapist-supervised training sessions per week, lasting 60 minutes each. In addition, all participants received a recommended caloric intake per day based on measured rest energy expenditure and a brochure regarding healthy diet in children
- Endpoints were physical fitness (maximal and submaximal exercise capacity, strength, and core stability), patient-reported outcomes (quality of life, fatigue, and fears for exercise), clinical disease activity (faecal calprotectin and disease activity scores), and nutritional status (energy balance and body composition)
- A total of 15 out of 16 participants (93%) completed the program, one patient dropped out after one training session due to motivational problems.
Results
The primary findings of this study were as follows:
- While medical treatment remained unchanged, Paediatric Crohn's Disease Activity Index decreased versus the control period (15 [3–25] vs 2.5 [0–5], P = 0.012)
- The number of patients in clinical remission increased from 5 to 12 (P < 0.001), compared to the control period
- Quality of life (IMPACT-III) improved on 4 out of 6 domains and the total score (+13 points) versus the control period including a large improvement in bowel-related symptoms, P= 0.029)
- Fecal calprotectin decreased, but not compared to the control period, mainly due to relatively large intra-patient fluctuations (400 μg/g [57.1–1662.7] vs 128 μg/g [23.8–642.3], P = 0.016)
- Parents reported an improvement in the quality of life versus the control period on the child health questionnaire and total fatigue score (PedsQoL • Multidimensional Fatigue Scale) (+14 points, P = 0.048)
- Walking distance improved after the 12-week program, compared to the control period (P = 0.001).
Conclusion
This study revealed that a 12-week physical training program and personalised dietary advice improved bowel symptoms, quality of life, and fatigue in children with IBD.
Clinical practice applications:
- The mechanism behind the anti-inflammatory effects of exercise has not been clarified
- Multiple theories have been suggested in previously published studies such as a reduced release of adipokines due to less visceral fat, increased secretion of anti-inflammatory cytokines such as interleukin (IL)-6, and reduced transient stool time
- This clinical trial demonstrated that a 12-week program of physical training sessions plus personalised healthy dietary advice resulted in improved physical fitness, quality of life, and parent-reported fatigue.
Considerations for future research:
- A sample size calculation was not provided in the study report and it is therefore assumed that the sample size of 16 children in this trial was too small to draw a definite conclusion. A larger study over a longer period is therefore needed across diverse age and ethnic population groups to draw better conclusions
- This study did not measure mucosal inflammation before and after the intervention due to the invasive nature of the procedure. It would however be useful that future research investigate this to gain more insight into the effect of lifestyle interventions on IBD.
Abstract
OBJECTIVES Physical activity programs have been suggested as adjunctive therapy in adult inflammatory bowel disease (IBD) patients. We assessed the effects of a 12-week lifestyle intervention in children with IBD. METHODS This study was a randomized semi-crossover controlled trial, investigating a 12-week lifestyle program (3 physical training sessions per week plus personalized healthy dietary advice) in children with IBD. Endpoints were physical fitness (maximal and submaximal exercise capacity, strength, and core stability), patient-reported outcomes (quality of life, fatigue, and fears for exercise), clinical disease activity (fecal calprotectin and disease activity scores), and nutritional status (energy balance and body composition). Change in maximal exercise capacity (peak VO 2 ) was the primary endpoint; all others were secondary endpoints. RESULTS Fifteen patients (median age 15 [IQR: 12-16]) completed the program. At baseline, peak VO 2 was reduced (median 73.3% [58.8-100.9] of predicted). After the 12-week program, compared to the control period, peak VO 2 did not change significantly; exercise capacity measured by 6-minute walking test and core-stability did. While medical treatment remained unchanged, Pediatric Crohn's Disease Activity Index decreased significantly versus the control period (15 [3-25] vs 2.5 [0-5], P = 0.012), and fecal calprotectin also decreased significantly but not versus the control period. Quality of life (IMPACT-III) improved on 4 out of 6 domains and total score (+13 points) versus the control period. Parents-reported quality of life on the child health questionnaire and total fatigue score (PedsQoL Multidimensional Fatigue Scale) also improved significantly versus the control period. CONCLUSIONS A 12-week lifestyle intervention improved bowel symptoms, quality of life, and fatigue in pediatric IBD patients.
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Are inflammatory markers associated with sarcopenia-related traits in older adults with sarcopenia? - A cross-sectional analysis of the ENHANce study.
Dupont, J, Vercauteren, L, Amini, N, Lapauw, L, De Schaepdryver, M, Poesen, K, Dedeyne, L, Verschueren, S, Tournoy, J, Koppo, K, et al
Experimental gerontology. 2023;178:112196
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Sarcopenia is a muscle disease, characterised by loss of muscle mass and function, leading to ‘muscle failure’. Primary sarcopenia is age-driven and one of the major mechanisms behind the onset and progression of sarcopenia is the chronic low grade inflammatory state related with ageing, the so-called ‘Inflammageing’. The aim of this study was to explore the levels of inflammatory markers (CRP, albumin, IL-1β, IL-6, IL-8 and TNF-α) in older adults with sarcopenia. This study was an exploratory, secondary, cross-sectional analysis. In total, 40 older adults (15 men and 25 women) with probable, confirmed, or severe sarcopenia were included. Results showed subclinical low levels of inflammatory markers in older adults suffering from sarcopenia, compatible with age-related Inflammageing. Positive associations were found between the examined inflammatory markers and sarcopenia-related traits. Furthermore, gender had a significant influence on the associations between these inflammatory markers and sarcopenia-related traits. Authors concluded that their findings stress the complexity of the inflammageing-sarcopenia interplay and the importance of not only looking at muscle mass or the sarcopenia construct when researching sarcopenia, but also considering other sarcopenia-related traits and gender in future research.
Abstract
AIMS: To explore the relationship between inflammatory markers and sarcopenia-related traits in sarcopenic older adults. METHODS Baseline data of the ongoing Exercise and Nutrition for Healthy AgeiNg (ENHANce) study were used for a secondary, exploratory, cross-sectional analysis. ENHANce is a 5-armed triple blinded randomized controlled trial, in older adults (>65y) with sarcopenia defined according to the revised criteria of the European Working Group of Sarcopenia in Older People (EWGSOP2) aiming to assess the effect of combined anabolic interventions (protein supplement, omega-3 supplement and physical exercise) on physical performance, compared to single/placebo interventions. Inflammatory markers C-reactive protein (hs-CRP), albumin, interleukin-1β (IL-1β), IL-6, IL-8, and tumour necrosis factor-α (TNF-α) were assessed at baseline. Spearman's rho (ρ) correlation coefficients were calculated to associate these inflammatory markers with baseline sarcopenia-defining parameters (handgrip strength, chair stand test, appendicular lean mass [aLM], gait speed, Short Physical Performance Battery), physical activity (step count) and quality of life (SF-36, SarQoL). RESULTS We included 40 sarcopenic subjects (15 men/25 women, age 77.1 ± 6.8 years). Contrary to expectations, the pro-inflammatory IL-1β correlated positively with handgrip strength (ρ: 0.376; p = 0.024) and IL-6 with aLM (ρ: 0.334; p = 0.0433). IL-6 inversely correlated with step count (ρ:-0.358; p = 0.048). Subgroup analysis revealed important gender differences. IL-8 inversely correlated with handgrip strength in women (ρ: -0.425; p = 0.034) but not in men. In contrast, pro-inflammatory cytokines CRP (ρ: -0.615; p = 0.019), IL-6 (ρ: -0.604; p = 0.029) and TNF-α (ρ: -0.615; p = 0.025) inversely correlated with the SF-36 physical component score in men but not in women. CONCLUSION Although Inflammageing might play a role in sarcopenia-related traits, this exploratory study highlights an important role of gender. Future research should take this into account when elucidating the Inflammageing-sarcopenia interplay.
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Effects of dietary fibers or probiotics on functional constipation symptoms and roles of gut microbiota: a double-blinded randomized placebo trial.
Lai, H, Li, Y, He, Y, Chen, F, Mi, B, Li, J, Xie, J, Ma, G, Yang, J, Xu, K, et al
Gut microbes. 2023;15(1):2197837
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Functional constipation is characterised by continuously difficult, incomplete, or infrequent defecation, without an organic origin. Effective intervention strategies are required to relieve the functional constipation difficulties, particularly in rapidly aging populations, such as Chinese populations. The aim of this study was to evaluate the effectiveness of three dietary fibre formulas (polydextrose, psyllium husk, and wheat bran + psyllium husk) and one probiotic supplement on the improvement of constipation symptoms among Chinese adults with functional constipation. This study was a double-blinded randomised placebo-controlled trial which enrolled 250 participants who were randomly assigned to one of the five groups. Results showed: - that daily supplement of three prebiotic formulas with dietary fibres, or a probiotic formula effectively relieved hard stool in functional constipation patients after 4 weeks intervention. - the capacity of gut microbial genera in shaping the intervention responsiveness in the improvement of bowel movement frequency, Bristol stool scale score, and degree of defecation straining. Authors conclude that the pre or probiotic interventions may modulate gut microbiota, associated with intestinal health.
Abstract
Dietary fibers/probiotics may relieve constipation via optimizing gut microbiome, yet with limited trial-based evidences. We aimed to evaluate the effects of formulas with dietary fibers or probiotics on functional constipation symptoms, and to identify modulations of gut microbiota of relevance. We conducted a 4-week double-blinded randomized placebo-controlled trial in 250 adults with functional constipation. Intervention: A: polydextrose; B: psyllium husk; C: wheat bran + psyllium husk; D: Bifidobacterium animalis subsp. lactis HN019 + Lacticaseibacillus rhamnosus HN001; Placebo: maltodextrin. Oligosaccharides were also included in group A to D. 16S rRNA sequencing was used to assess the gut microbiota at weeks 0, 2, and 4. A total of 242 participants completed the study. No time-by-group effect was observed for bowel movement frequency (BMF), Bristol stool scale score (BSS), and degree of defecation straining (DDS), while BSS showed mean increases of 0.95-1.05 in group A to D (all P < 0.05), but not significantly changed in placebo (P = 0.170), and 4-week change of BSS showed similarly superior effects of the interventions as compared placebo. Group D showed a marginal reduction in plasma 5-hydroxytryptamine. Group A resulted in a higher Bifidobacterium abundance than placebo at week 2 and 4. Fourteen genera showed intervention-specific increasing or decreasing trends continuously, among which Anaerostipes showed increasing trends in groups B and C, associated with BMF increase. Random forest models identified specific baseline microbial genera panels predicting intervention responders. In conclusion, we found that the dietary fibers or probiotics may relieve hard stool, with intervention-specific changes in gut microbiota relevant to constipation relief. Baseline gut microbiota may predispose the intervention responsiveness. ClincialTrials.gov number, NCT04667884. What is the context?Supplementation of dietary fibers, such as psyllium husk or wheat bran (10 ~ 15 g/day) may relieve constipation symptoms, but bloating and flatulence are major concerns on a high fiber intake.Functional constipation patients had alternated gut microbiota profiles, while meta-analysis suggested that multispecies probiotics may increase bowel movement frequency and relieve hard stool in functional constipation.Dietary fibers or probiotics may lead to before-after changes of gut microbiota in patients with functional constipation, but time-series continued changes of gut microbiota during the intervention are unknown.Elevation of 5-hydroxytryptamine synthesis in enterochromaffin cells may affect bowel movement. And the elevated plasma 5-hydroxytryptamine was observed in functional constipation patients.What is new? Daily supplement of three prebiotic formulas with dietary fibers (polydextrose, psyllium husk, wheat bran, together with oligosaccharides), or a probiotic formula with Bifidobacterium animalis subsp. lactis HN019 + Lacticaseibacillus rhamnosus HN001 effectively relieved hard stool in functional constipation patients after 4 weeks intervention.We identified continued increasing or decreasing gut microbial genera over the intervention. Dietary fiber – gut microbiota (Anaerostipes)—constipation relieve (bowel movement frequency) evidence axis was identified in this human trial.Probiotic supplementation marginally reduced plasma 5-hydroxytryptamine, possibly associated with changes in BMF-related gut microbial genera.Intervention-specific baseline gut microbiota well predicted the responsiveness of constipation symptom relief.What is the impact? We provided references for the dosage and duration of dietary fiber/probiotics recommendations for adults with functional constipation, and advanced the microbial genera evidences of the fibers/probiotics-microbiota-laxation theory in humans.
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High-fiber diet ameliorates gut microbiota, serum metabolism and emotional mood in type 2 diabetes patients.
Chen, L, Liu, B, Ren, L, Du, H, Fei, C, Qian, C, Li, B, Zhang, R, Liu, H, Li, Z, et al
Frontiers in cellular and infection microbiology. 2023;13:1069954
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Accumulating studies have demonstrated that there are strong correlations between type 2 diabetes mellitus (T2DM) and gut microbiota. A nutritious diet composed of an adequate level of dietary fibres could provide enough carbohydrates for the gut microbiota to ferment, and the microbial metabolites could provide energy supply and regulate the immune function of the host. The aim of this study was to analyse the changes in gut microbiota, serum metabolism and emotional mood of patients with T2DM after consumption of a high-fibre diet. This study was a randomised, open-label, parallel-group clinical trial in T2DM patients with a 4-week treatment period. Seventeen patients clinically diagnosed with T2DM enrolled in the clinical trial and were randomly assigned into two groups: the control group (n = 8) or the intervention group (n = 9). Results showed that the high-fibre diet (compared to the control group): - improved glucose homeostasis and lipid metabolism of participants with T2DM; - decreased serum levels of inflammatory chemokines in participants with T2DM; - alleviated depression and anxiety symptoms, particularly by the uptake of more diverse carbohydrates in the diet in participants with T2DM; - enhanced the diversity of gut microbiota in the treatment group. Authors conclude that the dietary source of fibre demonstrated protective impacts on the gut ecosystem, and the alteration of the gut microbiota composition improved the glucose homeostasis in patients with T2DM.
Abstract
Previous studies have demonstrated that patients with type 2 diabetes mellitus (T2DM) often had the problems of fecal microbiota dysbiosis, and were usually accompanied with psychiatric comorbidities (such as depression and anxiety). Here, we conducted a randomized clinical study to analyze the changes in gut microbiota, serum metabolism and emotional mood of patients with T2DM after consumption of a high-fiber diet. The glucose homeostasis of participants with T2DM was improved by the high-fiber diet, and the serum metabolome, systemic inflammation and psychiatric comorbidities were also altered. The increased abundances of Lactobacillus, Bifidobacterium and Akkermansias revealed that the proportions of beneficial gut microbes were enriched by the high-fiber diet, while the abundances of Desulfovibrio, Klebsiella and other opportunistic pathogens were decreased. Therefore, the current study demonstrated that the intestinal microbiota alterations which were influenced by the high-fiber diet could improve the serum metabolism and emotional mood of patients with T2DM.
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Sleep disruption and activation of cellular inflammation mediate heightened pain sensitivity: a randomized clinical trial.
Irwin, MR, Olmstead, R, Bjurstrom, MF, Finan, PH, Smith, MT
Pain. 2023;164(5):1128-1137
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Sleep disturbance is associated with elevated levels of inflammation. Experimental studies have found that even a modest amount of sleep loss activates inflammatory processes. Experimental sleep disruption also induces alterations in sleep architecture including loss of slow wave or N3 sleep and loss of rapid eye movement sleep. The aim of this study was to clarify whether changes in the amount of N3 sleep and cellular inflammation mediate thermal pain sensitivity (i.e., heat pain threshold) in response to experimental sleep disruption. This study was a secondary analysis (assessor-blind) of a randomised controlled trial. The enrolled participants were randomised to 1 of 2 groups: 2 nights of undisturbed sleep (US) and 2 nights of sleep disruption or forced awakening (FA). Participants underwent 2 consecutive nights of US (or FA), followed by a 2-week washout interval in their home environment, and then completed 2 consecutive nights of the opposing sleep condition FA (or US). Results showed that in healthy adults, experimental disruption of sleep due to the administration of FA induced a significant decrease in heat pain threshold, as compared with responses after US. Experimental manipulation of sleep with FA also led to disturbance in sleep continuity and changes in sleep architecture, including loss of N3 sleep. Moreover, in the morning after FA, there was a robust activation of cellular inflammation Authors conclude that the differential loss of N3 sleep and increases in cellular inflammation may be important drivers of pain sensitivity in response to sleep disruption.
Abstract
Sleep loss heightens pain sensitivity, but the pathways underlying this association are not known. Given that experimental sleep disruption induces increases in cellular inflammation as well as selective loss of slow wave, N3 sleep, this study examined whether these mechanisms contribute to pain sensitivity following sleep loss in healthy adults. This assessor-blinded, cross-over sleep condition, single-site, randomized clinical trial enrolled 95 healthy adults (mean [SD] age, 27.8 [6.4]; female, 44 [53.7%]). The 2 sleep conditions were 2 nights of undisturbed sleep (US) and 2 nights of sleep disruption or forced awakening (FA, 8 pseudorandomly distributed awakenings and 200 minutes wake time during the 8-hour sleep opportunity), administered in a cross-over design after 2 weeks of washout and in a random order (FA-US; US-FA). Primary outcome was heat pain threshold (hPTH). Sleep architecture was assessed by polysomnography, and morning levels of cellular inflammation were evaluated by Toll-like receptor-4 stimulated monocyte intracellular proinflammatory cytokine production. As compared with US, FA was associated with decreases in the amount of slow wave or N3 sleep ( P < 0.001), increases in Toll-like receptor-4 stimulated production of interleukin-6 and tumor necrosis factor-α ( P = 0.03), and decreases in hPTH ( P = 0.02). A comprehensive causal mediation analysis found that FA had an indirect effect on hPTH by decreases in N3 sleep and subsequent increases in inflammation (estimate=-0.15; 95% confidence interval, -0.30 to -0.03; P < 0.05) with the proportion mediated 34.9%. Differential loss of slow wave, N3 sleep, and increases in cellular inflammation are important drivers of pain sensitivity after sleep disruption.Clinical Trials Registration: NCT01794689.
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A Mediterranean Diet Pattern Improves Intestinal Inflammation Concomitant with Reshaping of the Bacteriome in Ulcerative Colitis: A Randomised Controlled Trial.
Haskey, N, Estaki, M, Ye, J, Shim, RK, Singh, S, Dieleman, LA, Jacobson, K, Gibson, DL
Journal of Crohn's & colitis. 2023;17(10):1569-1578
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Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) with debilitating symptoms. Patients live with considerable symptom burden, increased risk of disability, and lower quality of life despite medical treatment. The aim of this study was to investigate the efficacy of the Mediterranean Diet Pattern (MDP) compared with a Canadian Habitual Diet Pattern (CHD) on UC disease activity, inflammation, and the gut microbiome. This study was a randomised controlled trial where participants were randomly assigned to follow the MDP or CHD for 12 weeks. Results showed that: - the MDP reduces clinical symptoms and reduces inflammation. - the MDP promotes faecal secretory immunoglobulin A [the principal weapon protecting us from pathogens and toxins that might otherwise penetrate mucosal surfaces. - the MDP is positively associated with microbes that produce potentially beneficial metabolites. - the MDP is negatively associated with microbes predicted to carry pathobiont traits. - the MDP increases faecal short-chain fatty acids production. Authors conclude that the MDP is well tolerated and is a reasonable, healthy eating pattern that practitioners can recommend to patients with UC in remission to prevent relapses, in addition to their standard medical therapy.
Abstract
BACKGROUND AND AIMS Dietary patterns are important in managing ulcerative colitis [UC], given their influence on gut microbiome-host symbiosis and inflammation. We investigated whether the Mediterranean Diet Pattern [MDP] vs the Canadian Habitual Diet Pattern [CHD] would affect disease activity, inflammation, and the gut microbiome in patients with quiescent UC. METHODS We performed a prospective, randomised, controlled trial in adults [65% female; median age 47 years] with quiescent UC in an outpatient setting from 2017 to 2021. Participants were randomised to an MDP [n = 15] or CHD [n = 13] for 12 weeks. Disease activity [Simple Clinical Colitis Activity Index] and faecal calprotectin [FC] were measured at baseline and week 12. Stool samples were analysed by 16S rRNA gene amplicon sequencing. RESULTS The diet was well tolerated by the MDP group. At week 12, 75% [9/12] of participants in the CHD had an FC >100 μg/g, vs 20% [3/15] of participants in the MDP group. The MDP group had higher levels of total faecal short chain fatty acids [SCFAs] [p = 0.01], acetic acid [p = 0.03], and butyric acid [p = 0.03] compared with the CHD. Furthermore, the MDP induced alterations in microbial species associated with a protective role in colitis [Alistipes finegoldii and Flavonifractor plautii], as well as the production of SCFAs [Ruminococcus bromii]. CONCLUSIONS An MDP induces gut microbiome alterations associated with the maintenance of clinical remission and reduced FC in patients with quiescent UC. The data support that the MDP is a sustainable diet pattern that could be recommended as a maintenance diet and adjunctive therapy for UC patients in clinical remission. ClinicalTrials.gov no: NCT0305371.
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The Effects of Black Tea Consumption on Intestinal Microflora-A Randomized Single-Blind Parallel-Group, Placebo-Controlled Study.
Tomioka, R, Tanaka, Y, Suzuki, M, Ebihara, S
Journal of nutritional science and vitaminology. 2023;69(5):326-339
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Tea from the leaves of the tea plant (Camelia sinensis) is consumed around the world. Tea has many health benefits, and in part, this is due to its rich content in compounds classed as polyphenols. Through the fermentation process, black tea is particularly high in polyphenols. Previous studies around respiratory infections indicated that regular consumption of black tea appeared to improve immune defence mechanisms that protect mucous membranes, called mucosal immunity. As this mucosal immunity is closely influenced by gut bacteria, the authors speculated whether the previously seen impact of improved mucosal immunity is related to the ability of black tea to also modulate bacteria in the gut. A previously run randomised single-blinded, placebo-controlled trial with 72 Japanese participants who consumed three cups of black tea (2g) or a placebo of barley tea for 12 weeks provided the data for this study. Data gathered included gut flora analysis, short-chain fatty acids (SCFAs) levels - fats that play a role in maintaining gut health, and saliva IgA (SIgA) concentrations - which are antibodies made in the lymph tissue of the gut. The results showed that black tea consumption led to a significant increase in the abundance of Prevotella bacteria, which mediate SCFA production and are involved in normalising immune function. Furthermore, tea increased butyrate-producing bacteria. Butyrate is associated with improved barrier function of the gut walls but also helps to manage pathogens and immune responses. Black tea consumption also increased salivary SIgA concentration - a type of antibody on the mucous membranes that prevents pathogens from entering the body -, and a decrease in stool acetic acid concentration, which may be due to the increase in butyrate-producing bacteria which use acetic acid to make butyrate. Notably, participants with low salivary SIgA levels at the start had a more pronounced positive change in total bacteria, after consuming black tea compared to the placebo group. The authors concluded that regular consumption of black tea may help to improve mucosal immunity by increasing the abundance of beneficial bacteria in the gut.
Abstract
We previously reported that black tea consumption for 12 wk reduced the risk of acute upper respiratory tract inflammation, and improved secretory capacity in individuals with low salivary SIgA levels (Tanaka Y et al. 2021. Jpn Pharmacol Ther 49: 273-288). These results suggested that habitual black tea consumption improves mucosal immunity. Therefore, in this study we evaluated the effect of black tea intake on gut microbiota, which is known to be involved in mucosal immunity, by analyzing the bacterial flora and the short-chain fatty acids (SCFAs) concentration of feces collected during the above clinical study. The clinical design was a randomized, single-blind, parallel-group, placebo-controlled study with 72 healthy Japanese adult males and females, who consumed three cups of black tea (Black Tea Polymerized Polyphenols 76.2 mg per day) or placebo per day for 12 wk. In all subjects intake of black tea significantly increased abundance of Prevotella and decreased fecal acetic acid concentration. Particularly in the subjects with low salivary SIgA levels, the change over time of total bacteria, Prevotella, and butyrate-producing bacteria, which are involved in normalizing immune function, were higher in the black tea group than in the placebo group. In subjects with low abundance of Flavonifractor plautii a butyrate-producing bacteria, black tea consumption significantly increased salivary SIgA concentration and the absolute number of Flavonifractor plautii. In conclusion, our results suggest that improvement of mucosal immunity via an increase in butyrate-producing bacteria in the gut may partly contribute to the suppressive effect of black tea consumption on acute upper respiratory tract inflammation observed in our previous report.
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Effects of galactooligosaccharides on maternal gut microbiota, glucose metabolism, lipid metabolism and inflammation in pregnancy: A randomized controlled pilot study.
Wan, J, An, L, Ren, Z, Wang, S, Yang, H, Ma, J
Frontiers in endocrinology. 2023;14:1034266
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During pregnancy, a disordered gut microbiome and abnormal glucose metabolism may be possible mechanisms for pregnancy complications such as gestational diabetes mellitus (GDM). Different from probiotics, galactooligosaccharides (GOS) is a prebiotic that is not digested and absorbed by the host, but can selectively promote the metabolism and proliferation of beneficial bacteria in the body, particularly Lactobacillus and Bifidobacterium. The aim of this study was to evaluate the feasibility, acceptability, and safety of prebiotic intervention in healthy pregnant women, and conduct a preliminary exploration of the possible benefits for pregnant women. This study was a prospective double-blinded randomised clinical trial involving pregnant women. Participants were randomly assigned to the control group and the intervention group at a 1:1 ratio. Results showed that GOS intervention had no significant effect on reducing the incidence of GDM and improving glucose and lipid metabolism. Furthermore, there was no significant difference in glucose and lipid metabolism levels between GOS group and placebo group. Authors conclude that GOS can be considered as a dietary supplement during pregnancy. However, further clinical studies are needed to strengthen the findings of this study.
Abstract
BACKGROUND Gut microbiota of pregnant women change with the gestational week. On the one hand, they participate in the metabolic adaptation of pregnant women. On the other hand, the abnormal composition of gut microbiota of pregnant women is more likely to suffer from gestational diabetes mellitus (GDM). Therefore, gut microbiota targeted treatment through dietary supplements is particularly important for prevention or treatment. Prebiotic supplements containing galactooligosaccharides (GOS) may be an intervention method, but the effect is still unclear. OBJECTIVE This study aims to evaluate the feasibility and acceptability of prebiotic intervention in healthy pregnant women during pregnancy, and to explore the possible effects of intervention on pregnant women and the influence on gut microbiota as preliminaries. METHODS After recruitment in first trimester, 52 pregnant women were randomly assigned to receive GOS intervention or placebo containing fructooligosaccharides. 16S rRNA sequencing technology was used to detect the composition, diversity and differential flora of gut microbiota. Lipid metabolism, glucose metabolism and inflammatory factors during pregnancy were also analyzed. RESULTS The adverse symptoms of GOS intervention are mild and relatively safe. For pregnant women, there was no significant difference in the GDM incidence rates and gestational weight gain (GWG) in the GOS group compared with placebo (P > 0.05). Compared with the placebo group, the levels of FPG, TG, TC, HDL-C LDL-C, and IL-6 had no significant difference in GOS group (P > 0.05). For newborns, there was no significant difference between GOS group and placebo group in the following variables including gestational week, birth weight, birth length, head circumference, chest circumference, sex, and delivery mode (P > 0.05). And compared with the placebo group, the GOS group had a higher abundance of Paraprevotella and Dorea, but lower abundance of LachnospiraceaeUCG_001. CONCLUSIONS GOS prebiotics appear to be safe and acceptable for the enrolled pregnancies. Although GOS intervention did not show the robust benefits on glucose and lipid metabolism. However, the intervention had a certain impact on the compostion of gut microbiota. GOS can be considered as a dietary supplement during pregnancy, and further clinical studies are needed to explore this in the future.