Comprehensive insight into the alterations in the gut microbiome and the intestinal barrier as a consequence of iron deficiency anaemia.

BACKGROUND: Iron deficiency is the top leading cause of anaemia, whose treatment has been shown to deteriorate gut health. However, a comprehensive analysis of the intestinal barrier and the gut microbiome during IDA have not been performed to date. This study aims to delve further into the analysis of these two aspects, which will mean a step forward minimising the negative impact of iron supplements on intestinal health. METHODS: IDA was experimentally induced in an animal model. Shotgun sequencing was used to analyse the gut microbiome in the colonic region, while the intestinal barrier was studied through histological analyses, mRNA sequencing (RNA-Seq), qPCR and immunofluorescence. Determinations of lipopolysaccharide (LPS) and bacteria-specific immunoglobulins were performed to assess microbial translocation. RESULTS: Microbial metabolism in the colon shifted towards an increased production of certain amino acids, short chain fatty acids and nucleotides, with Clostridium species being enriched during IDA. Structural alterations of the colonic epithelium were shown by histological analysis. RNA-Seq revealed a downregulation of extracellular matrix-associated genes and proteins and an overall underdeveloped epithelium. Increased levels of serum LPS and an increased immune response against dysbiotic bacteria support an impairment in the integrity of the gut barrier during IDA. CONCLUSIONS: IDA negatively impacts the gut microbiome and the intestinal barrier, triggering an increased microbial translocation. This study emphasizes the deterioration of gut health during IDA and the fact that it should be addressed when treating the disease.

A Graph-Based Molecular Communications Model Analysis of the Human Gut Bacteriome.

Alterations in the human Gut Bacteriome (GB) can be associated with human health issues, such as type-2 diabetes and obesity. Both external and internal factors can drive changes in the composition and in interactions of the human GB, impacting negatively on the host cells. This paper focuses on the human GB metabolism and proposes a two-layer network system to investigate its dynamics. Furthermore, we develop an in-silico simulation model (virtual GB), allowing us to study the impact of the metabolite exchange through molecular communications in the human GB network system. Our results show that regulation of molecular inputs strongly affects bacterial population growth and creates an unbalanced network, as shown by shifts in the node weights based on the produced molecular signals. Additionally, we show that the metabolite molecular communication production is greatly affected when directly manipulating the composition of the human GB network in the virtual GB. These results indicate that our human GB interaction model can help to identify hidden behaviours of the human GB depending on molecular signal interactions. Moreover, the virtual GB can support the research and development of novel medical treatments based on the accurate control of bacterial population growth and exchange of metabolites.

Alpha-synuclein alters the faecal viromes of rats in a gut-initiated model of Parkinson's disease.

Parkinson's disease (PD) is a chronic neurological disorder associated with the misfolding of alpha-synuclein (α-syn) into aggregates within nerve cells that contribute to their neurodegeneration. Recent evidence suggests α-syn aggregation may begin in the gut and travel to the brain along the vagus nerve, with microbes potentially a trigger initiating α-syn misfolding. However, the effects α-syn alterations on the gut virome have not been investigated. In this study, we show longitudinal faecal virome changes in rats administered either monomeric or preformed fibrils (PFF) of α-syn directly into their enteric nervous system. Differential changes in rat viromes were observed when comparing monomeric and PFF α-syn, with alterations compounded by the addition of LPS. Changes in rat faecal viromes were observed after one month and did not resolve within the study's five-month observational period. These results suggest that virome alterations may be reactive to host α-syn changes that are associated with PD development.

The effects of sustained fitness improvement on the gut microbiome: A longitudinal, repeated measures case-study approach.

The athlete gut microbiome differs from that of non-athletes in its composition and metabolic function. Short-term fitness improvement in sedentary adults does not replicate the microbiome characteristics of athletes. The objective of this study was to investigate whether sustained fitness improvement leads to pronounced alterations in the gut microbiome. This was achieved using a repeated-measures, case-study approach that examined the gut microbiome of two initially unfit volunteers undertaking progressive exercise training over a 6-month period. Samples were collected every two weeks, and microbiome, metabolome, diet, body composition, and cardiorespiratory fitness data were recorded. Training culminated in both participants completing their respective goals (a marathon or Olympic-distance triathlon) with improved body composition and fitness parameters. Increases in gut microbiota α-diversity occurred with sustained training and fluctuations occurred in response to training events (eg, injury, illness, and training peaks). Participants' BMI reduced during the study and was significantly associated with increased urinary measurements of N-methyl nicotinate and hippurate, and decreased phenylacetylglutamine. These results suggest that sustained fitness improvements support alterations to gut microbiota and physiologically-relevant metabolites. This study provides longitudinal analysis of the gut microbiome response to real-world events during progressive fitness training, including intercurrent illness and injury.

Protein quality and quantity influence the effect of dietary fat on weight gain and tissue partitioning via host-microbiota changes.

We investigated how protein quantity (10%-30%) and quality (casein and whey) interact with dietary fat (20%-55%) to affect metabolic health in adult mice. Although dietary fat was the main driver of body weight gain and individual tissue weight, high (30%) casein intake accentuated and high whey intake reduced the negative metabolic aspects of high fat. Jejunum and liver transcriptomics revealed increased intestinal permeability, low-grade inflammation, altered lipid metabolism, and liver dysfunction in casein-fed but not whey-fed animals. These differential effects were accompanied by altered gut size and microbial functions related to amino acid degradation and lipid metabolism. Fecal microbiota transfer confirmed that the casein microbiota increases and the whey microbiota impedes weight gain. These data show that the effects of dietary fat on weight gain and tissue partitioning are further influenced by the quantity and quality of the associated protein, primarily via effects on the microbiota.

In vitro-in vivo Validation of Stimulatory Effect of Oat Ingredients on Lactobacilli.

The prebiotic activity of a commercially available oat product and a novel oat ingredient, at similar ß-glucan loads, was tested using a validated in vitro gut model (M-SHIME®). The novel oat ingredient was tested further at lower ß-glucan loads in vitro, while the commercially available oat product was assessed in a randomised, single-blind, placebo-controlled, and cross-over human study. Both approaches focused on healthy individuals with mild hypercholesterolemia. In vitro analysis revealed that both oat products strongly stimulated Lactobacillaceae and Bifidobacteriaceae in the intestinal lumen and the simulated mucus layer, and corresponded with enhanced levels of acetate and lactate with cross-feeding interactions leading to an associated increase in propionate and butyrate production. The in vitro prebiotic activity of the novel oat ingredient remained at lower ß-glucan levels, indicating the prebiotic potential of the novel oat product. Finally, the stimulation of Lactobacillus spp. was confirmed during the in vivo trial, where lactobacilli abundance significantly increased in the overall population at the end of the intervention period with the commercially available oat product relative to the control product, indicating the power of in vitro gut models in predicting in vivo response of the microbial community to dietary modulation.

Fermented-Food Metagenomics Reveals Substrate-Associated Differences in Taxonomy and Health-Associated and Antibiotic Resistance Determinants.

Fermented foods have been the focus of ever greater interest as a consequence of purported health benefits. Indeed, it has been suggested that consumption of these foods helps to address the negative consequences of "industrialization" of the human gut microbiota in Western society. However, as the mechanisms via which the microbes in fermented foods improve health are not understood, it is necessary to develop an understanding of the composition and functionality of the fermented-food microbiota to better harness desirable traits. Here, we considerably expand the understanding of fermented-food microbiomes by employing shotgun metagenomic sequencing to provide a comprehensive insight into the microbial composition, diversity, and functional potential (including antimicrobial resistance and carbohydrate-degrading and health-associated gene content) of a diverse range of 58 fermented foods from artisanal producers from a number of countries. Food type, i.e., dairy-, sugar-, or brine-type fermented foods, was the primary driver of microbial composition, with dairy foods found to have the lowest microbial diversity. From the combined data set, 127 high-quality metagenome-assembled genomes (MAGs), including 10 MAGs representing putatively novel species of Acetobacter, Acidisphaera, Gluconobacter, Companilactobacillus, Leuconostoc, and Rouxiella, were generated. Potential health promoting attributes were more common in fermented foods than nonfermented equivalents, with water kefirs, sauerkrauts, and kvasses containing the greatest numbers of potentially health-associated gene clusters. Ultimately, this study provides the most comprehensive insight into the microbiomes of fermented foods to date and yields novel information regarding their relative health-promoting potential.IMPORTANCE Fermented foods are regaining popularity worldwide due in part to a greater appreciation of the health benefits of these foods and the associated microorganisms. Here, we use state-of-the-art approaches to explore the microbiomes of 58 of these foods, identifying the factors that drive the microbial composition of these foods and potential functional benefits associated with these populations. Food type, i.e., dairy-, sugar-, or brine-type fermented foods, was the primary driver of microbial composition, with dairy foods found to have the lowest microbial diversity and, notably, potential health promoting attributes were more common in fermented foods than nonfermented equivalents. The information provided here will provide significant opportunities for the further optimization of fermented-food production and the harnessing of their health-promoting potential.

Metabolic phenotyping of the human microbiome.

The human microbiome has been identified as having a key role in health and numerous diseases. Trillions of microbial cells and viral particles comprise the microbiome, each representing modifiable working elements of an intricate bioactive ecosystem. The significance of the human microbiome as it relates to human biology has progressed through culture-dependent (for example, media-based methods) and, more recently, molecular (for example, genetic sequencing and metabolomic analysis) techniques. The latter have become increasingly popular and evolved from being used for taxonomic identification of microbiota to elucidation of functional capacity (sequencing) and metabolic activity (metabolomics). This review summarises key elements of the human microbiome and its metabolic capabilities within the context of health and disease.

Moderate-intensity aerobic and resistance exercise is safe and favorably influences body composition in patients with quiescent Inflammatory Bowel Disease: a randomized controlled cross-over trial.

BACKGROUND: Overweight and metabolic problems now add to the burden of illness in patients with Inflammatory Bowel Disease. We aimed to determine if a program of aerobic and resistance exercise could safely achieve body composition changes in patients with Inflammatory Bowel Disease. METHODS: A randomized, cross-over trial of eight weeks combined aerobic and resistance training on body composition assessed by Dual Energy X-ray Absorptiometry was performed. Patients in clinical remission and physically inactive with a mean age of 25 ± 6.5 years and Body Mass Index of 28.9 ± 3.8 were recruited from a dedicated Inflammatory Bowel Disease clinic. Serum cytokines were quantified, and microbiota assessed using metagenomic sequencing. RESULTS: Improved physical fitness was demonstrated in the exercise group by increases in median estimated VO2max (Baseline: 43.41mls/kg/min; post-intervention: 46.01mls/kg/min; p = 0.03). Improvement in body composition was achieved by the intervention group (n = 13) with a median decrease of 2.1% body fat compared with a non-exercising group (n = 7) (0.1% increase; p = 0.022). Lean tissue mass increased by a median of 1.59 kg and fat mass decreased by a median of 1.52 kg in the exercising group. No patients experienced a deterioration in disease activity scores during the exercise intervention. No clinically significant alterations in the α- and ß-diversity of gut microbiota and associated metabolic pathways were evident. CONCLUSIONS: Moderate-intensity combined aerobic and resistance training is safe in physically unfit patients with quiescent Inflammatory Bowel Disease and can quickly achieve favourable body compositional changes without adverse effects. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov; Trial number: NCT02463916 .

A Prospective Metagenomic and Metabolomic Analysis of the Impact of Exercise and/or Whey Protein Supplementation on the Gut Microbiome of Sedentary Adults.

Many components of modern living exert influence on the resident intestinal microbiota of humans with resultant impact on host health. For example, exercise-associated changes in the diversity, composition, and functional profiles of microbial populations in the gut have been described in cross-sectional studies of habitual athletes. However, this relationship is also affected by changes in diet, such as changes in dietary and supplementary protein consumption, that coincide with exercise. To determine whether increasing physical activity and/or increased protein intake modulates gut microbial composition and function, we prospectively challenged healthy but sedentary adults with a short-term exercise regime, with and without concurrent daily whey protein consumption. Metagenomics- and metabolomics-based assessments demonstrated modest changes in gut microbial composition and function following increases in physical activity. Significant changes in the diversity of the gut virome were evident in participants receiving daily whey protein supplementation. Results indicate that improved body composition with exercise is not dependent on major changes in the diversity of microbial populations in the gut. The diverse microbial characteristics previously observed in long-term habitual athletes may be a later response to exercise and fitness improvement. IMPORTANCE The gut microbiota of humans is a critical component of functional development and subsequent health. It is important to understand the lifestyle and dietary factors that affect the gut microbiome and what impact these factors may have. Animal studies suggest that exercise can directly affect the gut microbiota, and elite athletes demonstrate unique beneficial and diverse gut microbiome characteristics. These characteristics are associated with levels of protein consumption and levels of physical activity. The results of this study show that increasing the fitness levels of physically inactive humans leads to modest but detectable changes in gut microbiota characteristics. For the first time, we show that regular whey protein intake leads to significant alterations to the composition of the gut virome.

The microbiome of professional athletes differs from that of more sedentary subjects in composition and particularly at the functional metabolic level.

OBJECTIVE: It is evident that the gut microbiota and factors that influence its composition and activity effect human metabolic, immunological and developmental processes. We previously reported that extreme physical activity with associated dietary adaptations, such as that pursued by professional athletes, is associated with changes in faecal microbial diversity and composition relative to that of individuals with a more sedentary lifestyle. Here we address the impact of these factors on the functionality/metabolic activity of the microbiota which reveals even greater separation between exercise and a more sedentary state. DESIGN: Metabolic phenotyping and functional metagenomic analysis of the gut microbiome of professional international rugby union players (n=40) and controls (n=46) was carried out and results were correlated with lifestyle parameters and clinical measurements (eg, dietary habit and serum creatine kinase, respectively). RESULTS: Athletes had relative increases in pathways (eg, amino acid and antibiotic biosynthesis and carbohydrate metabolism) and faecal metabolites (eg, microbial produced short-chain fatty acids (SCFAs) acetate, propionate and butyrate) associated with enhanced muscle turnover (fitness) and overall health when compared with control groups. CONCLUSIONS: Differences in faecal microbiota between athletes and sedentary controls show even greater separation at the metagenomic and metabolomic than at compositional levels and provide added insight into the diet-exercise-gut microbiota paradigm.