Baseline Microbiota Composition Research Articles

Short-Term Supplementation of Sauerkraut Induces Favorable Changes in the Gut Microbiota of Active Athletes: A Proof-of-Concept Study.

Since the gut microbiota is important for athlete health and performance, its optimization is increasingly gaining attention in sports nutrition, for example, with whole fermented foods. Sauerkraut is a traditional fermented food rich in pro-, pre-, and postbiotics, which has not yet been investigated in the field of sports nutrition. To determine whether sauerkraut could be used for gut microbiota optimization in sports nutrition, a proof-of-concept study was conducted. The microbiota composition of organic pasteurized sauerkraut was analyzed, and then healthy active athletes were provided with the same sauerkraut for 10 days as an intervention. The effects of sauerkraut on the athlete's gut microbiota, laboratory parameters, and bowel function were assessed. Significant changes in the gut microbiota composition were seen on taxonomic and functional levels, independent of baseline microbiota composition, even after short-term supplementation. Most notably, there was an increase in several health-promoting genera of the family Lachnospiraceae, as well as significant alterations in metabolic pathways regarding cell wall synthesis and the metabolism of nucleotide bases. An increase in the proportion of lymphocytes and a decrease in B12 vitamin levels was observed, as well as a risk of indigestion in certain athletes, which significantly resolved after seven days of supplementation in all athletes. It is unclear whether the observed effects are attributable to the sauerkraut's own microbiome or its pre- and postbiotics since it is a whole food. Our study has demonstrated that the concept of whole fermented foods, such as sauerkraut, could potentially be feasible and effective in sports nutrition for gut microbiota optimization.

O88 REDUCTION IN SYSTOLIC BLOOD PRESSURE FOLLOWING DIETARY FIBRE INTERVENTION IS DEPENDENT ON BASELINE GUT MICROBIOTA COMPOSITION

Background/Objective: Dietary interventions high in fibre have been shown to lower blood pressure (BP). This effect is via the gut microbiota, via fermentation of fibre and production of metabolites called short-chain fatty acids (SCFAs). Not all patients respond to dietary fibre interventions for unclear reasons. We aimed to determine if we can identify fibre-responders based on their gut microbiota and production of SCFAs. Methods: We performed a phase II cross-over placebo-controlled randomised clinical trial in untreated hypertensive patients. Twenty treatment-naive participants with hypertension received 40 g per day of fermentable fibre delivered as acetylated and butyrylated high amylose maize starch (HAMSAB) or the placebo for 3 weeks. Blood pressure was monitored at baseline and endpoint by ambulatory BP monitoring, with those experiencing a reduction of ≥2 mmHg in systolic BP classified as responders. The microbiota was determined by sequencing the V4-V5 region of the 16S rRNA gene in baseline stool samples. The relationship between baseline gut microbiota and response to dietary intervention was assessed with the MaAsLin2 package. Plasma SCFAs levels were quantified by mass spectrometry. Results: We observed a placebo-subtracted mean 24-hour systolic BP of –6.1 mmHg (p=0.03, reported in Jama et al., 2023 Nature Cardiovascular Research), with 14 (70%) individuals classified as responders and 6 (30%) as non-responders. Genera significantly enriched in responders included Dialister (β=1.29, q=1.921x10-134), Coprococcus (β=1.26, q=3.282x10-121), Bifidobacterium (β=1.67, q=1.11x10-81), Ruminococcus (β=0.161, q=1.11x10-8), and Roseburia (β=0.82, q=4.275x10-2). Responders also produced higher levels of the SCFAs butyrate (mean±SEM, non-responders 4.95±2.4 vs responders 51.15±14.7, p=0.0096), but no difference in other SCFAs. Conclusions: Participants who experienced a decrease in systolic BP following a dietary fibre intervention had increased bacterial genera known to contain species that produce SCFAs (Bifidobacterium, Roseburia, Ruminococcus) at baseline, and were able to produce more butyrate. These data suggest that baseline microbiota composition contributes to the response to dietary fibre intervention trials in people with hypertension, likely via increased capacity to produce butyrate.

Examination of sex-specific interactions between gut microbiota and host metabolism after 12-week combined polyphenol supplementation in individuals with overweight or obesity

ABSTRACT Polyphenols exert beneficial effects on host metabolism, which may be mediated by the gut microbiota. We investigated sex-specific differences in microbiota composition and interactions with cardiometabolic parameters after polyphenol supplementation in individuals with overweight/obesity. In a double-blind, randomized, placebo-controlled trial, 19 women and 18 men with normal glucose tolerance and body mass index >25 kg/m2 received epigallocatechin-3-gallate and resveratrol (EGCG+RES, 282 + 80 mg/d) or placebo supplements for 12 weeks. Fecal microbiota composition (16S rRNA gene amplicon sequencing, V3-V4 region), in vivo whole-body fat oxidation (indirect calorimetry), and mitochondrial respiration in permeabilized skeletal muscle fibers (SkM-Ox; ex vivo respirometry) were determined pre- and post-intervention. Overall, EGCG+RES supplementation did not affect gut microbiota composition. Akkermansia, Ruminococcaceae UCG-002, Subdoligranulum, and Lachnospiraceae UCG-004 were more abundant, while Veillonella, Tyzzerella 4, Clostridium innocuum group, Ruminococcus gnavus group, Escherichia-Shigella, and an uncultured Ruminococcaceae family genus were less abundant in women compared to men. In women, only baseline Eubacterium ventriosum group abundance correlated with EGCG+RES-induced changes in SkM-Ox. In men, low Dorea, Barnsiella, Anaerotruncus, Ruminococcus, Subdoligranulum, Coprococcus, Eubacterium ventriosum group, Ruminococcaceae UCG-003, and a Ruminococcaceae family genus abundance, and high Blautia abundance at baseline were associated with improvements in SkM-Ox. Changes in whole-body fat oxidation were not associated with gut microbiota features. We conclude that baseline microbiota composition predicts changes in SkM-Ox as a result of EGCG+RES supplementation in men but not in women. Men may be more prone to diet-induced, gut microbiota-related improvements in cardiometabolic health. These sex-differences should be further investigated in future precision-based intervention studies.

O-279 The lower reproductive tract microbiota composition alters upon ovarian stimulation and is associated with, but not accurately predictive of reproductive outcomes following ART

Abstract Study question Are ovarian stimulation (OS) and ART success associated with the microbiota of the lower reproductive tract (LRT), i.e. vagina and cervix? Summary answer Estrogen rise during OS has a pivotal role in the LRT microbiota variation. The LRT microbiota pre-OS, although associated, may not accurately predict ART success. What is known already OS is a key component to enhance success rates in ART. OS triggers a significant rise in serum estrogen levels, which are known to influence the vaginal microbiota. The role of the female LRT microbiota in ART success is increasingly recognized, yet the impact of OS, particularly the estrogen rise, on these microbial communities and how the change may influence ART success remains largely unknown. Additionally, finding putative biomarkers within LRT microbiota could aid in predicting ART success. Understanding this relationship could refine and personalize fertility treatments, but robust evidence is needed to guide microbiota-based clinical decisions in ART. Study design, size, duration Vaginal and cervical swabs were collected longitudinally from patients undergoing ART and this at baseline (pre-OS) and at oocyte retrieval (post-OS). We gathered a final dataset comprising 275 vaginal samples at baseline and 240 samples at oocyte retrieval. Additionally, we defined a prospective cohort of n = 228x2 samples corresponding to patients for which both pre- and post-OS samples were available. The main results as detected within the vaginal samples were confirmed in the cervical samples. Participants/materials, setting, methods Bacterial DNA from −80 °C preserved swabs was extracted in a Tecan Nucleic Acid Extraction Platform, using the QIAamp DNA-Stool-Mini-Kit. Samples for paired-end Illumina MiSeq were constructed using a two-step PCR amplicon approach targeting the V4 region of the 16S rRNA. Then, LotuS, DADA2, the RDP classifier trainset 16 and variance stabilisation (poscounts, DESeq2) were used for read de-multiplexing, pre-processing, taxonomy assignment and transformation, respectively, as recommended for zero-inflated compositional data. Main results and the role of chance First, a confounder analysis revealed that both the menstrual phase and intercourse correlated with the LRT’s baseline microbiota composition (multivariate distance-based redundancy analysis [dbRDA], AdjP<0.05, N = 275). Next, in the paired cohort, we observed that the OS-associated rise in estrogen was correlated with confounder-independent compositional (confounder-adjusted dbRDA, AdjP=0.002, R2=1.14%, N = 228x2) and microbial-feature changes (Wilcoxon test, AdjP<0.05, Ndelta=228) in the LRT. Interestingly, post-OS we noted a decrease in Lactobacillus proportions compared to baseline (in participants sampled at either the follicular or luteal phase of the menstrual cycle). Additionally, post-OS microbiota composition was not associated with the live birth rate (LBR, following the first embryo transfer of the cycle) or the cumulative LBR (CLBR, following all embryo transfers of the cycle), nor with the total number of high-quality (HQ) embryos available (dbRDA, AdjP>0.05, N = 240). Notably, pre-OS microbiota communities and LRT Anaerococcus and Peptoniphilus proportions were associated with (C)LBR (confounder-adjusted dbRDA, AdjP<0.05; Logistic regression, odds-ratio<1, AdjP<0.05, N = 275). Machine learning models determined that vaginal Peptoniphilus and Anaerococcusproportions alone did not have good accuracy/ROC for predicting (C)LBR (test-set;<70%). Notably, the number of HQ embryos showed good accuracy/ROC for CLBR (test-set; 80%/84.5%). Including vaginal Anaerococcus proportions only slightly improved the model’s accuracy/ROC (test-set; 82.5%/85.6%). Limitations, reasons for caution The data’s proportional nature restricted assessing whether the estrogen rise decreased Lactobacillus proportions or increased other bacteria. Luteal phase sampling was avoided given the intravaginal progesterone support. Larger datasets may further improve predictive models. Wider implications of the findings Our study highlights the confounding impact of baseline variables and the influence of the OS-associated estrogen rise on LRT microbiota. It questions the clinical relevance of the LRT microbiota’s impact on reproductive outcomes following ART, warning for caution in microbiota-based decisions in ART. Trial registration number NCT03105453

Gut microbiome composition and functionality impact the responsiveness to a dairy-based product containing galacto-oligosaccharides for improving sleep quality in adults.

Sleep quality and duration can be impacted by diet, and has been linked to gut microbiota composition and function as the result of communication via the microbiota-gut-brain axis. As one strategy to improve sleep quality could be through the modulation of the gut microbiome, we assessed the effects of a dairy-based product containing whey protein, galacto-oligosaccharides, tryptophan, vitamins and minerals after a 3 weeks intervention on gut microbiota composition and (gut-brain related) functions on basis of 67 healthy subjects with moderate sleep disturbances. Associations of the gut microbiota with sleep quality and with response/non-response to the treatment were revealed by shotgun metagenomics sequencing of faecal DNA samples, and subsequent analyses of microbiota taxonomy and generic functionality. A database of manually curated Gut-Brain Modules (GBMs) was applied to analyse specific microbial functions/pathways that have the potential to interact with the brain. A moderate discriminating effect of the DP treatment on gut microbiota composition was revealed which could be mainly attributed to a decrease in Pseudomonas resinovorans, Flintibacter sp. KGM00164, Intestinimonas butyriciproducens, and Flavonifractor plautii. As interindividual variance in microbiota composition could have given rise to a heterogenous responsiveness of the subjects in the intervention group, we zoomed in on the differences between responders and non-responders. A significant difference in baseline microbiota composition between responders and non-responders was apparent, showing lower Bifidobacterium longum and Bifidobacterium adolescentis, and higher Faecalibacterium prausnitzii relative abundances in responders. The findings provide leads with respect to the effectiveness and potential underlying mechanisms of mode of action in sleep improvement that could support future nutritional interventions to aid sleep improvement.

Reduction in systolic blood pressure following dietary fibre intervention is dependent on baseline gut microbiota composition

Uncontrolled hypertension is a primary cause of non-communicable diseases and death globally(1). The gut microbiota plays a role in hypertension and dietary interventions high in fibre have been shown to lower blood pressure (BP)(2). Not all participants respond to dietary fibre interventions, for reasons which are unclear. Here we aimed to identify responders of a high fibre intervention based on their baseline gut microbiome. Twenty treatment-naive participants with hypertension received either placebo or 40g per day of prebiotic acetylated and butyrylated high amylose maize starch (HAMSAB) supplementation for 3 weeks in a phase II randomised cross-over double-blind placebo-controlled trial. Blood pressure was monitored at baseline and each endpoint by 24-hour ambulatory BP monitoring, with those experiencing a reduction between timepoints of ≥ 2 mmHg classified as responders. Baseline stool samples were collected and the V4-V5 region of the 16S gene sequenced. Taxonomy was assigned by reference to the SILVA database. The MaAsLin2 package was used for assessing the relationship between baseline gut microbiota and response to dietary intervention. Overall participants had significant reduction in 24-hour systolic BP (–6.1 mmHg, p = 0.03), with 14 individuals classified as responders and six individuals as non-responders. 13 genera were found to be differentially abundant between responders and non-responders. Genera significantly enriched in responders included Dialister (β = 1.29, q = 1.921x10-134), Coprococcus (β = 1.26, q = 3.282x10-121), Bifidobacterium (β = 1.67, q = 1.11x10-81), Ruminococcus (β = 0.161, q = 1.11x10-8) and Roseburia (β = 0.82, q = 4.275x10-2). Participants who experienced a decrease in systolic BP following a dietary fibre intervention had increased level of bacterial genera known to contain species that produce short-chain fatty acids (e.g. Bifidobacterium, Roseburia and Ruminococcus) at baseline. These data suggest that baseline microbiota composition contributes to the response to dietary fibre intervention trials in people with hypertension.

Intestinal microbiota signatures of clinical response and immune-related adverse events in melanoma patients treated with anti-PD-1.

Ample evidence indicates that the gut microbiome is a tumor-extrinsic factor associated with antitumor response to anti-programmed cell death protein-1 (PD-1) therapy, but inconsistencies exist between published microbial signatures associated with clinical outcomes. To resolve this, we evaluated a new melanoma cohort, along with four published datasets. Time-to-event analysis showed that baseline microbiota composition was optimally associated with clinical outcome at approximately 1 year after initiation of treatment. Meta-analysis and other bioinformatic analyses of the combined data show that bacteria associated with favorable response are confined within the Actinobacteria phylum and the Lachnospiraceae/Ruminococcaceae families of Firmicutes. Conversely, Gram-negative bacteria were associated with an inflammatory host intestinal gene signature, increased blood neutrophil-to-lymphocyte ratio, and unfavorable outcome. Two microbial signatures, enriched for Lachnospiraceae spp. and Streptococcaceae spp., were associated with favorable and unfavorable clinical response, respectively, and with distinct immune-related adverse effects. Despite between-cohort heterogeneity, optimized all-minus-one supervised learning algorithms trained on batch-corrected microbiome data consistently predicted outcomes to programmed cell death protein-1 therapy in all cohorts. Gut microbial communities (microbiotypes) with nonuniform geographical distribution were associated with favorable and unfavorable outcomes, contributing to discrepancies between cohorts. Our findings shed new light on the complex interaction between the gut microbiome and response to cancer immunotherapy, providing a roadmap for future studies.

Effect of Concurrent Training on Body Composition and Gut Microbiota in Postmenopausal Women with Overweight or Obesity.

Menopause tends to be associated with an increased risk of obesity and abdominal fat mass (FM) and is associated with lower intestinal species diversity. The aim of this study was to determine the effects of a high-intensity interval training and resistance training (HIIT + RT) program on body composition and intestinal microbiota composition in overweight or obese postmenopausal women. Participants (n = 17) were randomized in two groups: HIIT + RT group (3× per week, 12 wk) and control group without any training. Dual-energy x-ray absorptiometry was used to measure whole-body and abdominal/visceral FM and fat-free mass. Intestinal microbiota composition was determined by 16S rRNA gene sequencing at baseline and at the study end, and the diet was controlled. Compared with sedentary controls, physical fitness (maximal oxygen consumption, peak power output) increased, total abdominal and visceral FM decreased, and segmental muscle mass increased in the training group. Although the HIIT + RT protocol did not modify α-diversity and taxonomy, it significantly influenced microbiota composition. Moreover, various intestinal microbiota members were correlated with HIIT + RT-induced body composition changes, and baseline microbiota composition predicted the response to the HIIT + RT program. HIIT + RT is an effective modality to reduce abdominal/visceral FM and improve physical capacity in nondieting overweight or obese postmenopausal women. Training modified intestinal microbiota composition, and the response to training seems to depend on the initial microbiota profile. More studies are needed to determine whether microbiota composition could predict the individual training response.

Sepsis-Induced Myopathy and Gut Microbiome Dysbiosis: Mechanistic Links and Therapeutic Targets.

Sepsis is currently defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. The skeletal muscle system is among the host organ systems compromised by sepsis. The resulting neuromuscular dysfunction and impaired regenerative capacity defines sepsis-induced myopathy and manifests as atrophy, loss of strength, and hindered regeneration after injury. These outcomes delay recovery from critical illness and confer increased vulnerability to morbidity and mortality. The mechanisms underlying sepsis-induced myopathy, including the potential contribution of peripheral organs, remain largely unexplored. The gut microbiome is an immunological and homeostatic entity that interacts with and controls end-organ function, including the skeletal muscle system. Sepsis induces alterations in the gut microbiota composition, which is globally termed a state of "dysbiosis" for the host compared to baseline microbiota composition. In this review, we critically evaluate existing evidence and potential mechanisms linking sepsis-induced myopathy with gut microbiota dysbiosis.

The Effect of A Whey-Protein and Galacto-Oligosaccharides Based Product on Parameters of Sleep Quality, Stress, and Gut Microbiota in Apparently Healthy Adults with Moderate Sleep Disturbances: A Randomized Controlled Cross-Over Study.

People experiencing sleep problems may benefit from nutrients supporting serotonin metabolism and stress reduction. We studied the effect of a dairy-based product (DP) containing protein, galacto-oligosaccharides, vitamins and minerals, on sleep quality, stress, and gut-microbiota. In a cross-over RCT (three weeks intervention; three weeks washout), adults (n = 70; 30–50 y) with sleep disturbances (Pittsburgh Sleep Quality Index (PSQI) ≥ 9) consumed products 1 h before bed-time. Sleep quality (PSQI) was measured weekly, stress at base- and end-line (Depression Anxiety Stress Scale and saliva cortisol). Fecal samples were collected in the 1st intervention period only. Compared to placebo (skimmed milk), PSQI was only lower at day 14 in the 2nd intervention period in intention-to-treat (ITT) (p = 0.017; n = 69) and per-protocol (PP) (p = 0.038; n = 64) analyses. Post-hoc analysis (modified-PP: n=47, with baseline PSQI ≥ 9, and endline day 14), however, showed a decrease in PSQI (−1.60 ± 2.53; p = 0.034). Early morning saliva cortisol decreased versus placebo (p = 0.045). Relative abundance of Bifidobacterium increased (p = 0.02). Redundancy analysis showed an inverse relationship between baseline microbiota composition and baseline PSQI (p = 0.046). Thus, although DP did not improve sleep quality in ITT and PP populations, it did in the modPP. DP reduced salivary cortisol and stimulated Bifidobacterium, which possibly is important for sleep improvement.

Daily Fermented Whey Consumption Alters the Fecal Short-Chain Fatty Acid Profile in Healthy Adults.

Gut microbiota influences many aspects of host health including immune, metabolic, and gut health. We examined the effect of a fermented whey concentrate (FWC) drink rich in L-(+)-Lactic acid, consumed daily, in 18 healthy men (n = 5) and women (n = 13) in free-living conditions.Objective: The aims of this 6-weeks pilot trial were to (i) identify changes in the gut microbiota composition and fecal short chain fatty acid (SCFA) profile, and (ii) to monitor changes in glucose homeostasis.Results: Total fecal SCFA (mM) concentration remained constant throughout the intervention. Proportionally, there was a significant change in the composition of different SCFAs compared to baseline. Acetate levels were significantly reduced (−6.5%; p < 0.01), coupled to a significant increase in the relative amounts of propionate (+2.2%; p < 0.01) and butyrate (+4.2%; p < 0.01), respectively. No changes in the relative abundance of any specific bacteria were detected. No significant changes were observed in glucose homeostasis in response to an oral glucose tolerance test.Conclusion: Daily consumption of a fermented whey product led to significant changes in fecal SCFA metabolite profile, indicating some potential prebiotic activity. These changes did not result in any detectable differences in microbiota composition. Post-hoc analysis indicated that baseline microbiota composition might be indicative of participants likely to see changes in SCFA levels. However, due to the lack of a control group these findings would need to be verified in a rigorously controlled trial. Future work is also required to identify the biological mechanisms underlying the observed changes in microbiota activity and to explore if these processes can be harnessed to favorably impact host health.Clinical Trial Registration: www.clinicaltrials.gov, identifier NCT03615339; retrospectively registered on 03/08/2018.

Infant gut microbiota characteristics generally do not modify effects of lipid-based nutrient supplementation on growth or inflammation: secondary analysis of a randomized controlled trial in Malawi

An unhealthy gut microbial community may act as a barrier to improvement in growth and health outcomes in response to nutritional interventions. The objective of this analysis was to determine whether the infant microbiota modified the effects of a randomized controlled trial of lipid-based nutrient supplements (LNS) in Malawi on growth and inflammation at 12 and 18 months, respectively. We characterized baseline microbiota composition of fecal samples at 6 months of age (n = 506, prior to infant supplementation, which extended to 18 months) using 16S rRNA gene sequencing of the V4 region. Features of the gut microbiota previously identified as being involved in fatty acid or micronutrient metabolism or in outcomes relating to growth and inflammation, especially in children, were investigated. Prior to correction for multiple hypothesis testing, the effects of LNS on growth appeared to be modified by Clostridium (p-for-interaction = 0.02), Ruminococcus (p-for-interaction = 0.007), and Firmicutes (p-for-interaction = 0.04) and effects on inflammation appeared to be modified by Faecalibacterium (p-for-interaction = 0.03) and Streptococcus (p-for-interaction = 0.004). However, after correction for multiple hypothesis testing these findings were not statistically significant, suggesting that the gut microbiota did not alter the effect of LNS on infant growth and inflammation in this cohort.

The relationship between epigenetics and microbiota in neuropsychiatric diseases.

Microbiota might be considered as a pool for environmental epigenetic factors. Evidence is accumulating that environmental exposures-including microbes, diet, drugs-play a role in the pathogenesis of many neuropsychiatric disorders. Underlying mechanisms are complex, involving the sensitive interplay of genetics with epigenetics, neuroinflammation and the innate immune system. Modifications of microbiota affect neurogenesis and the maturation of microglia, influencing social behavior, stress-related responses and fear learning mechanisms. The excitatory neurons in the medial prefrontal cortex appear to play a key role. The mechanisms through which antibiotics administration may modulate microbiotaand, therefore, behavior and neuropsychiatric disorders, may be influenced by several variables such as pre-existing gastrointestinal inflammation, the baseline microbiota composition, diet and stress perception.Probiotics, individualized diet, antibiotics and fecal transplantation could positively modulate the effects of epigenetic factors on neuropsychiatric disorders.

Long-term dietary intervention reveals resilience of the gut microbiota despite changes in diet and weight

With the rising rates of obesity and associated metabolic disorders, there is a growing need for effective long-term weight-loss strategies, coupled with an understanding of how they interface with human physiology. Interest is growing in the potential role of gut microbes as they pertain to responses to different weight-loss diets; however, the ways that diet, the gut microbiota, and long-term weight loss influence one another is not well understood. Our primary objective was to determine if baseline microbiota composition or diversity was associated with weight-loss success. A secondary objective was to track the longitudinal associations of changes to lower-carbohydrate or lower-fat diets and concomitant weight loss with the composition and diversity of the gut microbiota. We used 16S ribosomal RNA gene amplicon sequencing to profile microbiota composition over a 12-mo period in 49 participants as part of a larger randomized dietary intervention study of participants consuming either a healthy low-carbohydrate or a healthy low-fat diet. While baseline microbiota composition was not predictive of weight loss, each diet resulted in substantial changes in the microbiota 3-mo after the start of the intervention; some of these changes were diet specific (14 taxonomic changes specific to the healthy low-carbohydrate diet, 12 taxonomic changes specific to the healthy low-fat diet) and others tracked with weight loss (7 taxonomic changes in both diets). After these initial shifts, the microbiota returned near its original baseline state for the remainder of the intervention, despite participants maintaining their diet and weight loss for the entire study. These results suggest a resilience to perturbation of the microbiota's starting profile. When considering the established contribution of obesity-associated microbiotas to weight gain in animal models, microbiota resilience may need to be overcome for long-term alterations to human physiology. This trial was registered at clinicaltrials.gov as NCT01826591.

Impact of short-term overfeeding of saturated or unsaturated fat or sugars on the gut microbiota in relation to liver fat in obese and overweight adults.

Intestinal microbiota may be causally involved in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). We aimed to study the effect of short-term overfeeding on human gut microbiota in relation to baseline and overfeeding-induced liver steatosis. We also asked whether the baseline microbiota composition is associated to the overfeeding-induced increase in liver fat. In a randomized trial, 38 overweight and obese subjects were assigned to consume an excess of 1000kcal/day of diets rich in either saturated fat, unsaturated fat, or simple sugars for 3 weeks. Fasting blood samples and 1H-MR spectroscopy were used for extensive clinical phenotyping as previously reported (PMID: 29844096). Fecal samples were collected for the analysis of the gut microbiota using 16S rRNA amplicon sequencing, imputed metagenomics and qPCR. Microbiota results were correlated with dietary intakes and clinical measurements before and during overfeeding. The overall community structure of the microbiota remained highly stable and personalized during overfeeding based on between-sample Bray-Curtis dissimilarity, but the relative abundances of individual taxa were altered in a diet-specific manner: overfeeding saturated fat increased Proteobacteria, while unsaturated fat increased butyrate producers. Sugar overfeeding increased Lactococcus and Escherichia coli. Imputed functions of the gut microbiota were not affected by overfeeding. Several taxa affected by overfeeding significantly correlated with the changes in host metabolic markers. The baseline levels of proteobacterial family Desulfovibrionaceae, and especially genus Bilophila, were significantly associated to overfeeding-induced liver fat increase independently of the diet arm. In general, limited overlap was observed between the overfeeding-induced microbiota changes and the liver fat-associated microbiota features at baseline. Our work indicates that the human gut microbiota is resilient to short-term overfeeding on community level, but specific taxa are altered on diet composition-dependent manner. Generalizable microbiota signatures directly associated with liver steatosis could not be identified. Instead, the carriage of Bilophila was identified as a potential novel risk factor for diet-induced liver steatosis in humans. Clinical trial registry number: NCT02133144 listed on NIH website: ClinicalTrials.gov.

Infant microbiota in colic: predictive associations with problem crying and subsequent child behavior.

Infant colic is a condition of unknown cause which can result in carer distress and attachment difficulties. Recent studies have implicated the gut microbiota in infant colic, and certain probiotics have demonstrated possible efficacy. We aim to investigate whether the intestinal microbiota composition in infants with colic is associated with cry/fuss time at baseline, persistence of cry/fuss at 4-week follow-up, or child behavior at 2 years of age. Fecal samples from infants with colic (n = 118, 53% male) were analyzed using 16S rRNA sequencing. After examining the alpha and beta diversity of the clinical samples, we performed a differential abundance analysis of the 16S data to look for taxa that associate with baseline and future behavior, while adjusting for potential confounding variables. In addition, we used random forest classifiers to evaluate how well baseline gut microbiota can predict future crying time. Alpha diversity of the fecal microbiota was strongly influenced by birth mode, feed type, and child gender, but did not significantly associate with crying or behavioral outcomes. Several taxa within the microbiota (including Bifidobacterium, Clostridium, Lactobacillus, and Klebsiella) associate with colic severity, and the baseline microbiota composition can predict further crying at 4 weeks with up to 65% accuracy. The combination of machine learning findings with associative relationships demonstrates the potential prognostic utility of the infant fecal microbiota in predicting subsequent infant crying problems.

Baseline microbiota composition modulates antibiotic-mediated effects on the gut microbiota and host

BackgroundNormal mammalian development and homeostasis are dependent upon the gut microbiota. Antibiotics, essential for the treatment and prophylaxis of bacterial infections, can have collateral effects on the gut microbiota composition, which can in turn have far-reaching and potentially deleterious consequences for the host. However, the magnitude and duration of such collateral effects appear to vary between individuals. Furthermore, the degree to which such perturbations affect the host response is currently unclear. We aimed to test the hypothesis that different human microbiomes have different responses to a commonly prescribed antibiotic and that these differences may impact the host response.MethodsGerm-free mice (n = 30) humanized with the microbiota of two unrelated donors (A and B) were subjected to a 7-day antibiotic challenge with amoxicillin-clavulanate (“co-amoxiclav”). Microbiome and colonic transcriptome analysis was performed, pre (day 0) and post antibiotics (day 8) and subsequently into recovery (days 11 and 18).ResultsUnique community profiles were evident depending upon the donor, with donor A recipient mice being dominated by Prevotella and Faecalibacterium and donor B recipient mice dominated by Bacteroides and Parabacteroides. Donor A mice underwent a marked destabilization of their microbiota following antibiotic treatment, while donor B mice maintained a more stable profile. Dramatic and overlapping alterations in the host transcriptome were apparent following antibiotic challenge in both groups. Despite this overlap, donor A mice experienced a more significant alteration in gene expression and uniquely showed correlations between host pathways and key microbial genera.ConclusionsGerm-free mice humanized by different donor microbiotas maintain distinct microbiome profiles, which respond in distinct ways to antibiotic challenge and evince host responses that parallel microbiome disequilibrium. These results suggest that inter-individual variation in the gut microbiota may contribute to personalized host responses following microbiota perturbation.

Randomised clinical trial: effect of low-FODMAP rye bread versus regular rye bread on the intestinal microbiota of irritable bowel syndrome patients: association with individual symptom variation

BackgroundA low intake of Fermentable, Oligo-, Di-, Mono-saccharides and Polyols (FODMAPs) is effective in the symptom control of irritable bowel syndrome (IBS) patients but may exert negative effects on the intestinal microbiota. The microbial effects of increasing regular or non-FODMAP fibre sources are largely unknown. Furthermore, it is not known if the baseline microbiota composition is associated with individual symptom control during the consumption of different rye products in IBS patients. Our objective was to evaluate whether increased consumption of low-FODMAP rye bread or regular rye bread for 4 weeks would alter the intestinal microbiota composition of IBS patients following their habitual diet, and whether these changes associate to symptoms and/or the baseline microbiota.MethodsThe study was conducted as a randomized double blind controlled cross-over study (n = 50). Microbiota was analysed by 16S rRNA gene sequencing and associated with gastrointestinal symptoms. Both microbial changes and their associations to symptoms were secondary outcomes.ResultsThe consumption of the test breads did not alter microbiota diversity. Compared to baseline, consumption of the low FODMAP rye bread decreased the abundance of Bacteroides, Flavonifractor, Holdemania, Parasutterella and Klebsiella and showed a trend towards increased bifidobacteria, whereas the regular rye bread decreased the abundance of Flavonifractor. When comparing between the two test breads, Klebsiella was decreased after low-FODMAP rye bread intake. Patients whose symptoms decreased during the low-FODMAP rye bread displayed more Blautia and less Barnesiella at baseline.ConclusionsConsumption of low-FODMAP rye bread had modest, potentially beneficial effects on patients’ microbiota while increasing their intake of fibre substantially. The baseline microbiota composition was associated with the variable degrees of symptom relief experienced by the patients. Consumption of a low-FODMAP rye bread might be one way to increase dietary fibre intake and improve the mild dysbiosis often observed among patients with IBS.Trial registrationClinicalTrials.gov: NCT02161120. Retrospectively registered 11 June 2014.

A 12-wk whole-grain wheat intervention protects against hepatic fat: the Graandioos study, a randomized trial in overweight subjects

Whole-grain wheat (WGW) is described as nutritionally superior to refined wheat (RW) and thus advocated as the healthy choice, although evidence from intervention studies is often inconsistent. The liver, as the central organ in energy metabolism, might be an important target organ for WGW interventions. The aim of this study was to investigate the potential benefits of WGW consumption compared with RW consumption on liver health and associated parameters. We performed a double-blind, parallel trial in which 50 overweight 45- to 70-y-old men and postmenopausal women were randomly allocated to a 12-wk intervention with either WGW (98 g/d) or RW (98 g/d) products. Before and after the intervention we assessed intrahepatic triglycerides (IHTGs) and fat distribution by proton magnetic resonance spectroscopy/magnetic resonance imaging, fecal microbiota composition, adipose tissue gene expression, and several fasting plasma parameters, as well as postprandial plasma lipids after a mixed meal. Fasting plasma cholesterol, triglycerides, nonesterified fatty acids, and insulin were not affected by RW or WGW intervention. We observed a substantial increase of 49.1% in IHTGs in the RW when compared with the WGW group (P=0.033). Baseline microbiota composition could not predict the increase in IHTGs after RW, but gut microbiota diversity decreased in the RW group when compared with the WGW group (P=0.010). In the WGW group, we observed increased postprandial triglyceride levels compared with the RW group (P=0.020). In addition, the WGW intervention resulted in a trend towards lower fasting levels of the liver acute-phase proteins serum amyloid A (P=0.057) and C-reactive protein (P=0.064) when compared to the RW intervention. A 12-wk RW intervention increases liver fat and might contribute to the development of nonalcoholic fatty liver disease, whereas a 12-wk 98-g/d WGW intervention prevents a substantial increase in liver fat. Our results show that incorporating feasible doses of WGW in the diet at the expense of RW maintains liver health. The study was registered at clinicaltrials.gov as NCT02385149.

The Gut Microbiota of Healthy Aged Chinese Is Similar to That of the Healthy Young.

The microbiota of the aged is variously described as being more or less diverse than that of younger cohorts, but the comparison groups used and the definitions of the aged population differ between experiments. The differences are often described by null hypothesis statistical tests, which are notoriously irreproducible when dealing with large multivariate samples. We collected and examined the gut microbiota of a cross-sectional cohort of more than 1,000 very healthy Chinese individuals who spanned ages from 3 to over 100 years. The analysis of 16S rRNA gene sequencing results used a compositional data analysis paradigm coupled with measures of effect size, where ordination, differential abundance, and correlation can be explored and analyzed in a unified and reproducible framework. Our analysis showed several surprising results compared to other cohorts. First, the overall microbiota composition of the healthy aged group was similar to that of people decades younger. Second, the major differences between groups in the gut microbiota profiles were found before age 20. Third, the gut microbiota differed little between individuals from the ages of 30 to >100. Fourth, the gut microbiota of males appeared to be more variable than that of females. Taken together, the present findings suggest that the microbiota of the healthy aged in this cross-sectional study differ little from that of the healthy young in the same population, although the minor variations that do exist depend upon the comparison cohort. IMPORTANCE We report the large-scale use of compositional data analysis to establish a baseline microbiota composition in an extremely healthy cohort of the Chinese population. This baseline will serve for comparison for future cohorts with chronic or acute disease. In addition to the expected difference in the microbiota of children and adults, we found that the microbiota of the elderly in this population was similar in almost all respects to that of healthy people in the same population who are scores of years younger. We speculate that this similarity is a consequence of an active healthy lifestyle and diet, although cause and effect cannot be ascribed in this (or any other) cross-sectional design. One surprising result was that the gut microbiota of persons in their 20s was distinct from those of other age cohorts, and this result was replicated, suggesting that it is a reproducible finding and distinct from those of other populations.