Gut Flora

The human gut microbiome has been associated with many health factors but variability between studies limits exploration of effects between them. Gut microbiota profiles are available for >2700 members of the deeply phenotyped TwinsUK cohort, providing a uniform platform for such comparisons. Here, we present gut microbiota association analyses for 38 common diseases and 51 medications within the cohort. We describe several novel associations, highlight associations common across multiple diseases, and determine which diseases and medications have the greatest association with the gut microbiota. These results provide a reference for future studies of the gut microbiome and its role in human health.

Prebiotics may modify the biological processes in the chickens' gastrointestinal tract to improve poultry performance and health. Prebiotics are natural feed additives that offer many economic advantages by decreasing mortality rates, increasing growth rates, and improving birds' feed efficiency. Prebiotic action potentially affects the degradation of indigestible dietary compounds, the synthesis of nitrogen components and vitamins, and simplifies the removal of undesirable elements in the diet. Prebiotics could also induce desirable gut microbiome modifications and affect host metabolism and immune health. It is worth mentioning that gut bacteria metabolize the prebiotic compounds into organic compounds that the host can subsequently use. It is important to limit the concept of prebiotics to compounds that influence the metabolism of resident microorganisms. Any medicinal component or feed ingredient beneficial to the intestinal microecosystem can be considered a prebiotic. In this review, the impacts of prebiotics on the gut microbiome and physiological structure are discussed, emphasizing the poultry's growth performance. The current review will highlight the knowledge gaps in this area and future research directions.

The gut microbiota plays a fundamental role in host health and disease. Host diet is one of the most significant modulators of the gut microbial community and its metabolic activities. Evidence demonstrates that dietary patterns such as the ‘Western diet’ and perturbations in gut microbiome (dysbiosis) have strong associations with a wide range of human diseases, including obesity, metabolic syndrome, type-2 diabetes and cardiovascular diseases. However, consumption of Mediterranean-style diets is considered healthy and associated with the prevention of cardiovascular and metabolic diseases, colorectal cancers and many other diseases. Such beneficial effects of the Mediterranean diet might be attributed to high proportion of fibers, mono- and poly-unsaturated fatty acids, antioxidants and polyphenols. Concurrent literature has demonstrated beneficial modulation of the gut microbiome following a Mediterranean-style diet in humans as well as in experimental animal models such as roden...

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Recent findings regarding the influence of the microbiota in many inflammatory processes have provided a new way to treat diseases. Now, one may hypothesize that the origin of a plethora of diseases is related to the health of the gut microbiota and its delicate, although complex, interface with the epithelial and immune systems. The 'westernization' of diets, for example, is associated with alterations in the gut microbiota. Such alterations have been found to correlate directly with the increased incidence of diabetes and hypertension, the main causes of chronic kidney diseases (CKDs), which, in turn, have a high estimated prevalence. Indeed, data have arisen showing that the progression of kidney diseases is strictly related to the composition of the microbiota. Alterations in the gut microbiota diversity during CKDs do not only have the potential to exacerbate renal injury but may also contribute to the development of associated comorbidities, such as cardiovascular diseases and insulin resistance. In this review, we discuss how dysbiosis through alterations in the gut barrier and the consequent activation of immune system could intensify the progression of CKD and vice versa, how CKDs can modify the gut microbiota diversity and abundance.

Psoriasis has a multifactorial pathogenesis and recently it was shown that alterations in the skin and intestinal microbiome are involved in the pathogenesis of psoriasis. Therefore, microbiome restoration becomes a promising preventive/therapy strategy in psoriasis. In our pre-clinical study design using a mice model of induced psoriatic dermatitis (Ps) we have tested the proof-of-concept that IgY raised against pathological human bacteria resistant to antibiotics can alleviate psoriatic lesions and restore deregulated immune cell parameters. Besides clinical evaluation of the mice and histology of the developed psoriatic lesions, cellular immune parameters were monitored. Immune cells populations/subpopulations from peripheral blood and spleen cell suspensions that follow the clinical improvement were assessed using flow cytometry. We have quantified T lymphocytes (CD3ε+) with T-helper (CD4+CD8−) and T-suppressor/cytotoxic (CD8a+CD4−) subsets, B lymphocytes (CD3ε−CD19+) and NK cel...

Although it is generally accepted that dietary fiber is health promoting, the underlying immunological and molecular mechanisms are not well defined, especially with respect to cellulose, the most ubiquitous dietary fiber. Here, the impact of dietary cellulose on intestinal microbiota, immune responses and gene expression in health and disease was examined. Lack of dietary cellulose disrupted the age-related diversification of the intestinal microbiota, which subsequently remained in an immature state. Interestingly, one of the most affected microbial genera was Alistipes which is equipped with enzymes to degrade cellulose. Absence of cellulose changed the microbial metabolome, skewed intestinal immune responses toward inflammation, altered the gene expression of intestinal epithelial cells and mice showed increased sensitivity to colitis induction. In contrast, mice with a defined microbiota including A. finegoldii showed enhanced colonic expression of intestinal IL-22 and Reg3γ restoring intestinal barrier function. This study supports the epidemiological observations and adds a causal explanation for the health promoting effects of the most common biopolymer on earth.

Crosstalk between the gut microbiome and the host plays an important role in animal development and health. Small compounds are key mediators in this host–gut microbiome dialogue. For instance, tryptophan metabolites, generated by biotransformation of tryptophan through complex host–microbiome co-metabolism can trigger immune, metabolic, and neuronal effects at local and distant sites. However, the origin of tryptophan metabolites and the underlying tryptophan metabolic pathway(s) are not well characterized in the current literature. A large number of the microbial contributors of tryptophan metabolism remain unknown, and there is a growing interest in predicting tryptophan metabolites for a given microbiome. Here, we introduce TrpNet, a comprehensive database and analytics platform dedicated to tryptophan metabolism within the context of host (human and mouse) and gut microbiome interactions. TrpNet contains data on tryptophan metabolism involving 130 reactions, 108 metabolites and...

BackgroundYoung children are frequently exposed to antibiotics for otitis media and respiratory infections, with the potential for collateral consequences on the gut microbiome. The impact of antibiotic exposures to off-target microbes (i.e., bacteria not targeted by antibiotic treatment) and antibiotic resistance genes (ARGs) is unknown.MethodsWe used metagenomic sequencing data from paired stool samples collected prior to antibiotic exposure and at 1 year from over 200 infants and a difference-in-differences approach to assess the relationship between subsequent exposures and the abundance or compositional diversity of off-target microbes and ARGs while adjusting for covariates.ResultsBy 1 year, the relative abundance of multiple species and ARGs differed by antibiotic exposure. Compared to infants never exposed to antibiotics, Bacteroides vulgatus relative abundance increased by 1.72% (95%CI:0.19,3.24) while Bacteroides fragilis decreased by 1.56% (95%CI:-4.32,1.21). Bifidobacter...

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While the antimicrobial resistance profiles of cultured pathogens have been characterized in swine, the fluctuations in antimicrobial resistance genes (ARGs) associated with the developing gastrointestinal microbiota have not been elucidated. The objective of this study was to assess the impact of perinatal tulathromycin (TUL) metaphylaxis on the developmental dynamics of fecal microbiota and their accompanying antimicrobial resistome in pre-weaned piglets. Sixteen litters were given one of two treatments [control group (CONT; saline 1cc IM) and TUL group (TUL; 2.5 mg/kg IM)] directly after birth. Deep fecal swabs were collected at day 0 (prior to treatment), and again at days 5 and 20 post treatment. Shotgun metagenomic sequencing was performed on the extracted DNA, and the fecal microbiota structure and abundance of ARGs were assessed. Collectively, the swine fecal microbiota and their accompanying ARGs were diverse and established soon after birth. Across all samples, a total of 127 ARGs related to 19 different classes of antibiotics were identified. The majority of identified ARGs were observed in both experimental groups and at all-time points. The magnitude and extent of differences in microbial composition and abundance of ARGs between the TUL and CONT groups were statistically insignificant. However, both fecal microbiota composition and ARGs abundance were changed significantly between different sampling days. In combination, these results indicate that the perinatal TUL metaphylaxis has no measurable benefits or detriment impacts on fecal microbiota structure and abundance of ARGs in pre-weaned piglets.

Interaction between disease-microbiome associations and ageing has not been explored in detail. Here, using age/region-matched sub-sets, we analysed the gut microbiome differences across five major diseases in a multi-cohort dataset constituting more than 2500 individuals from 20 to 89 years old. We show that disease-microbiome associations display specific age-centric trends. Ageing-associated microbiome alterations towards a disease-like configuration occur in colorectal cancer patients, thereby masking disease signatures. We identified a microbiome disease response shared across multiple diseases in elderly subjects that is distinct from that in young/middle-aged individuals, but also a novel set of taxa consistently gained in disease across all age groups. A subset of these taxa was associated with increased frailty in subjects from the ELDERMET cohort. The relevant taxa differentially encode specific functions that are known to have disease associations.

Gut microbial communities of mosquitoes can influence vector susceptibility to pathogens, yet the factors that govern their composition remain poorly understood. We investigated the impact of host blood meal source on gut microbiota of Aedes aegypti L. Adult mosquitoes were fed on human, rabbit or chicken blood and their gut microbiota compared to those of sugar-fed and newly emerged adults. Microbial diversity was significantly reduced in blood-fed and sugar-fed mosquitoes but was restored to the levels of newly emerged adults' 7-days post blood meal. Microbial composition was strongly influenced by host blood meal source. Leucobacter spp., Chryseobacterium spp., Elizabethkingia spp. and Serratia spp. were characteristic of newly emerged adults and adults fed on chicken, rabbit, and human blood respectively. Sugar-fed mosquitoes had higher abundance of Pseudomonas spp. and unclassified Acetobacteraceae. Shifts in gut microbial communities in response to host blood meal source m...

Dietary methionine restriction is associated with improved health outcomes and an increase in lifespan in animal models. We have previously shown that an increase in dietary methionine induces alteration in the intestinal microbiome. The composition of the intestinal microbiota is a determinant of health and we, therefore, hypothesized that dietary methionine restriction would also induce changes in the murine microbiome. After one month on a methionine-restricted diet, five-month-old male and female C57BL/6 mice had decreased levels of serum methionine, without changes in body weight. We identified a decrease in the hepatic methylation status of animals fed a methionine-restricted diet compared to controls. This decrease was not associated with changes in DNA or protein methylation in the liver. In males, we saw an increase in families Bacteroidaceae and Verrucoccaceae (mostly A. mucinophila) and a decrease in Rumminococcaceae in animals fed a methionine-restricted diet compared to...

The intestinal bacteria are known to play a significant role in intestinal homoeostasis and the mucosal immune system. In vitro interactions of Ampicillin (0.5-2.0 mg mL À1), Amphotericin-B (25-200 mg mL À1) and Ciprofloxacin (50-500 ng mL À1) with Escherichia coli, Pseudomonas sp. (Gram-negative), Lactobacillus sp., Staphylococcus sp. (Gram-positive), total mixed population of gut bacteria and intestinal epithelial cells were studied. In vitro exposure of Ciprofloxacin showed significant dose-dependent inhibition throughout the growth phase in bacteria. Similar patterns of concentration-dependent changes in membrane transport enzymes and structural constituents, dehydrogenase activity associated with respiratory and energy-producing processes and esterase activity test linked to the general heterotrophic activity of the cell were observed in both bacteria and epithelial cells. The antibiotic effects were in the order of Amphotericin-B o Ampicillin o Ciprofloxacin. Validation studies were conducted using rat intestinal loops filled with different concentrations of antibiotics and incubated for 30 min. In situ changes in epithelial cell membrane enzymes and constituents also indicated similar trends as observed following in vitro exposures. The findings suggest that these antibiotics exert similar cytotoxic effects on intestinal epithelial cells and gut bacteria. Thus, gut bacteria can be used for in vitro screening of gastrointestinal-cellular toxicity caused by antibiotics.

In recent years, plant-origin bio-active compounds in foods (staple crops, fruit, vegetables, and others) have been gaining interest, and processes to consider them for public health recommendations are being presented and discussed in the literature. However, at times, it may be challenging to demonstrate causality, and there often is not a single compound–single effect relationship. Furthermore, it was suggested that health benefits may be due to metabolites produced by the host or gut microbiome rather than the food constituent per se. Over the years, compounds that were investigated were shown to increase gut microbial diversity, improve endothelial function, improve cognitive function, reduce bone loss, and many others. More recently, an additional and significant body of evidence further demonstrated the nutritional role and potential effects that plant-origin bio-active compounds might have on intestinal functionality (specifically the duodenal brush border membrane, morpholo...

Chronic disruption of the intestinal microbiota in adult cystic fibrosis (CF) patients is associated with local and systemic inflammation, and has been linked to the risk of serious comorbidities. Supplementation with high amylose maize starch (HAMS) might provide clinical benefit by promoting commensal bacteria and the biosynthesis of immunomodulatory metabolites. However, whether the disrupted CF gut microbiota has the capacity to utilise these substrates is not known. We combined metagenomic sequencing, in vitro fermentation, amplicon sequencing, and metabolomics to define the characteristics of the faecal microbiota in adult CF patients and assess HAMS fermentation capacity. Compared to healthy controls, the faecal metagenome of adult CF patients had reduced bacterial diversity and prevalence of commensal fermentative clades. In vitro fermentation models seeded with CF faecal slurries exhibited reduced acetate levels compared to healthy control reactions, but comparable levels o...

Probiotics have been defined by Collins and Gibson (1999) as "a live microbial feed supplement which beneficially affects the host animal by improving its intestinal balance". There is a relatively large volume of literature that supports the use of probiotics to prevent or treat intestinal disorders. Currently, the best studied probiotics are the lactic acid bacteria, particularly Lactobacillus sp and Bifidobacterium sp. The mucosal surface of the intestinal tract represents the largest interface between the body and its environment. An effective local immune is necessary to protect the organism against the invasion of noxious antigens and microbes. No other organ of the body harbors more immune cells than the gut-associated lymphoid tissue (GALT), and a tremendous amount of antibodies is secreted into the intestinal lumen to neutralize and exclude harmful antigens. The numerous studies have reported immune stimulating abilities for different bacterial species. For example, in vitro cytokine production of macrophages was stimulated by Bifidobacteria (Marin et al., 1997). Bifidobacterium longum as well as several other lactic acid bacteria have been found to increase the total amount of intestinal IgA. Lactobacillus casei was reported to have immune adjuvant activity (Perdigon et al., 1989) and Lactobacillus plantarum was shown to increase antibody production against Escherichia coli.

Different patterns of IF have been extensively studied in human subjects and animal models, and proven to improve numerous health conditions including obesity, impaired glucose tolerance, dyslipidemia, hypertension, fertility problems, liver impairment, and neurodegenerative diseases (1-13). Time-restricted feeding (TRF), which entails restricting food intake to a 6-8 h time period daily, is one of the classical IF models. Our previous study, using an ischemic-reperfusion model in mice, showed that TRF is protective against liver impairment (14), and hence was proposed as a potential intervention to be integrated into

There exists a close relationship between the human host and the intestinal microbiota, a mixed community of microorganisms that protect the intestine from being colonised by exogenous pathogens. The intestinal microbiota plays a crucial role in the nutrition and modulation of the host’s immune homeostasis. Dysbiosis is a microbial imbalance between pathogenic and protective bacteria: the former can become dominant and the latter underrepresented, leading to a degraded microbial diversity [1]. In a healthy individual, the microbiota is composed of bacteria, fungi, viruses and yeasts. The host/microbiota coexists in mutual harmony, named symbiosis, allowing both to function properly [2]. It should be noted that the balance of the intestinal microbial ecosystem can be disrupted by a number of factors, such as antibiotics, vaccinations, certain foods and stress. An intestinal bacterial disorder primarily manifests itself in terms of quantitative changes in bacterial location and in the...

In the current study, we aimed to investigate the association between gut microbiome composition and two physiological factors, BMI and age. We did not observe a significant relationship between occurrence of gut bacteria with BMI or age alone. On the other hand, we observed BMI and age together played an important role in impacting gut microbiota composition. Comparison of the microbiota of normal and obese subjects for the each of 20s and 50s group revealed 13 gut bacteria that show significantly different relative abundance in the two groups. We observed that certain organisms show opposite trends within the two age groups. Haemophilus parainfluenzae relative abundance was found to be increased in obese-20s group while reduced in obese-50s group. Relative abundance of organisms such as Mitsuokella jalaludini and Blautia obeum were reduced in obese-20s group while increased in obese-50s group as compared to the normal subjects of respective age group. On the other hand, a reductio...

Coronavirus disease 2019, or COVID-19, is a major challenge facing scientists worldwide. Alongside the lungs, the system of organs comprising the GI tract is commonly targeted by COVID-19. The dysbiotic modulations in the intestine influence the disease severity, potentially due to the ability of the intestinal microbiota to modulate T lymphocyte functions, i.e., to suppress or activate T cell subpopulations. The interplay between the lungs and intestinal microbiota is named the gut–lung axis. One of the most usual comorbidities in COVID-19 patients is type 2 diabetes, which induces changes in intestinal microbiota, resulting in a pro-inflammatory immune response, and consequently, a more severe course of COVID-19. However, changes in the microbiota in this comorbid pathology remain unclear. Metformin is used as a medication to treat type 2 diabetes. The use of the type 2 diabetes drug metformin is a promising treatment for this comorbidity because, in addition to its hypoglycemic a...

The metabolic syndrome (MetS) has become a global public health burden due to its link to cardiovascular disease and diabetes mellitus. The present study was designed to characterize the metabolic and cardiovascular disturbances, as well as changes in gut microbiota associated with high-fructose high-fat diet (HFFD)-induced MetS in Watanabe heritable hyperlipidemic (WHHL) rabbits. Twenty-one Watanabe rabbits were assigned to a control (n = 9) and HFFD (n = 12) groups, receiving a chow diet and a HFFD, respectively. During a 12-weeks protocol, morphological parameters were monitored; plasma fasting levels of lipids, glucose and insulin were measured and a glucose tolerance test (GTT) was performed. HOMA-IR was calculated. Cardiac function and vascular reactivity were evaluated using the Langendorff isolated heart and isolated carotid arteries methods, respectively. 16S rRNA sequencing of stool samples was used to determine gut microbial composition and abundance. HFFD-fed Watanabe rabbits exhibited increased fasting insulin (p < 0.03, 12 th week vs. Baseline), HOMA-IR (p < 0.03 vs. Control), area under the curve of the GTT (p < 0.02 vs. Control), triglycerides (p < 0.05, 12 th week vs. Baseline), TC (p < 0.01 vs. Control), LDL-C (p < 0.001 vs. Control). The HFFD group also displayed a significant decrease in intestinal microbial richness, evenness and diversity (FDR < 0.001, FDR < 0.0001, FDR < 0.01, respectively vs. Control group) and an increase in its Firmicutes/Bacteroidetes ratio (R = 3.39 in control vs. R = 28.24 in the HFFD group) indicating a shift in intestinal microbial composition and diversity. Our results suggest that HFFD induces insulin resistance and gut microbiota dysbiosis and accentuates dyslipidemia; and that, when subjected to HFFD, Watanabe rabbits might become a potential diet-induced MetS animal models with two main features, dyslipidemia and insulin resistance.