Gut Flora

Conveyance of pathogens between organisms causes communicable diseases. On the other hand, a non-communicable disease (NCD) was always thought to have no causative transmissible infective agents. Today, this clear distinction is increasingly getting blurred and NCDs are found to be associated with some transmissible components. The human microbiota carries a congregation of microbes, the majority and the most widely studied being bacteria in the gut. The adult human gut harbors ginormous inhabitant microbes, and the microbiome accommodates 150-fold more genes than the host genome. Microbial communities share a mutually beneficial relationship with the host, especially with respect to host physiology including digestion, immune responses, and metabolism. This review delineates the connection between environmental factors such as infections leading to gut dysbiosis and NCDs and explores the evidence regarding possible causal link between them. We also discuss the evidence regarding th...

Aquatic animals are consistently exposed to the threats of environmental deterioration and infection outbreaks because of the excessive use of antibiotics and synthetic drugs. This practice leads to the accumulation of residues in aquatic systems and the development of antimicrobial resistance among pathogens. Nature-based solutions, such as functional feeds containing synbiotics and their active components, such as probiotics, prebiotics, and postbiotics, play a crucial role in maintaining a healthy environment and promoting the well-being of animals in aquaculture. Drawing upon a thorough literature survey and experimental evidence, these agents have been shown beneficial to aquatic animals and their ecosystems. Consequently, these synbiotic agents and related components emerge as promising natural alternatives to traditional synthetic drugs and antibiotics in aquaculture.

Hypertension is a major global health challenge, as it represents the main risk factor for stroke and cardiovascular disease. It is a multifactorial clinical condition characterized by high and sustained levels of blood pressure, likely resulting from a complex interplay of endogenous and environmental factors. The gut microbiota has been strongly supposed to be involved but its role in hypertension is still poorly understood. In an attempt to fill this gap, here we characterized the microbial composition of fecal samples from 48 hypertensive and 32 normotensive Brazilian individuals by nextgeneration sequencing of the 16S rRNA gene. In addition, the cytokine production of peripheral blood samples was investigated to build an immunological profile of these individuals. We identified a dysbiosis of the intestinal microbiota in hypertensive subjects, featured by reduced biodiversity and distinct bacterial signatures compared with the normotensive counterpart. Along with a reduction in Bacteroidetes members, hypertensive individuals were indeed mainly characterized by increased proportions of Lactobacillus and Akkermansia while decreased relative abundances of well-known butyrate-producing commensals, including Roseburia and Faecalibacterium within the Lachnospiraceae and Ruminococcaceae families. We also observed an inflamed immune profile in hypertensive individuals with an increase in TNF/IFN-γ ratio, and in TNF and IL-6 production when compared to normotensive ones. Our work provides the first evidence of association of hypertension with altered gut microbiota and inflammation in a Brazilian population. While lending support to the existence of potential microbial signatures of hypertension, likely to be robust to age and geography, our findings point to largely neglected bacteria as potential contributors to intestinal homeostasis loss and emphasize the high vulnerability of hypertensive individuals to inflammation-related disorders.

Human Campylobacter jejuni infections are of worldwide importance and represent the most commonly reported bacterial enteritis cases in middle-and high-income countries. Since antibiotics are usually not indicated and the severity of campylobacteriosis is directly linked to the risk of developing post-infectious complications, non-toxic antibiotic-independent treatment approaches are highly desirable. Given its health-promoting properties, including anti-microbial and anti-inflammatory activities, we tested the disease-alleviating effects of oral menthol in murine campylobacteriosis. Therefore, human gut microbiota-associated IL-10 -/-mice were orally subjected to synthetic menthol starting a week before C. jejuni infection and followed up until day 6 postinfection. Whereas menthol pretreatment did not improve campylobacteriosis symptoms, it resulted in reduced colonic C. jejuni numbers and alleviated both macroscopic and microscopic aspects of C. jejuni infection in pretreated mice vs. controls. Menthol pretreatment dampened the recruitment of macrophages, monocytes, and T lymphocytes to colonic sites of infection, which was accompanied by mitigated intestinal nitric oxide secretion. Furthermore, menthol pretreatment had only marginal effects on the human fecal gut microbiota composition during the C. jejuni infection. In conclusion, the results of this preclinical placebo-controlled intervention study provide evidence that menthol application constitutes a promising way to tackle acute campylobacteriosis, thereby reducing the risk for post-infectious complications.

The intestinal microbiota has come to be considered an additional risk factor for the development of metabolic diseases. Considering the potential role of antimicrobials as modulators of the intestinal microbiota, they have been investigated for use in the adjuvant treatment of obesity and insulin resistance (IR). In this regard, the present manuscript aimed to review the effect of regular use of antimicrobials on the treatment of obesity and/or IR, as well as its associated mechanisms. The regular use of antimicrobials does not seem to influence the body weight and adiposity of its consumer. Regarding IR, clinical trials did not observe positive effects, on the other hand, most of the experimental studies observed an increase in insulin sensitivity. The mechanisms used by antimicrobials that could lead to the improvement of insulin sensitivity are dependent on the modulation of the intestinal microbiota. This modulation would lead to a reduction in the stimulation of the immune sys...

Neuroinflammation has been implicated as a common cause of neurodegenerative disease including Alzheimer’s disease (AD). It results primarily from the activation of microglia that produces neurotoxic mediators and pro-inflammatory cytokines leading to neuronal death. Currently, research support nutritional interventions that include foods enriched with antioxidants to prevent AD and there is an increasing interest in the use of probiotics as a neuroprotective agent. In the present study, the protective effect of six lactobacilli strains (LAB 1, LAB 9, LAB 10, LAB 11, LAB 12 and LABPC) fermented in three different milk types [soymilk (SM-LAB), cow’s milk (CM-LAB) and goat’s milk (GM-LAB)] against lipopolysaccharide (LPS)-induced neuroinflammation in microglial BV2 cells was determined in vitro. The ability of the lactobacilli-fermented milk types to prevent memory deficit in LPS-induced mice was also investigated. Anti-inflammatory response against nitric oxide (NO) and CD40 expressi...

Background: Diarrheal diseases continue to contribute significantly to morbidity and mortality in infants and young children in developing countries. There is an urgent need to better understand the contributions of novel, potentially uncultured, diarrheal pathogens to severe diarrheal disease, as well as distortions in normal gut microbiota composition that might facilitate severe disease. Results: We use high throughput 16S rRNA gene sequencing to compare fecal microbiota composition in children under five years of age who have been diagnosed with moderate to severe diarrhea (MSD) with the microbiota from diarrhea-free controls. Our study includes 992 children from four low-income countries in West and East Africa, and Southeast Asia. Known pathogens, as well as bacteria currently not considered as important diarrhea-causing pathogens, are positively associated with MSD, and these include Escherichia/Shigella, and Granulicatella species, and Streptococcus mitis/pneumoniae groups. In both cases and controls, there tend to be distinct negative correlations between facultative anaerobic lineages and obligate anaerobic lineages. Overall genus-level microbiota composition exhibit a shift in controls from low to high levels of Prevotella and in MSD cases from high to low levels of Escherichia/Shigella in younger versus older children; however, there was significant variation among many genera by both site and age. Conclusions: Our findings expand the current understanding of microbiota-associated diarrhea pathogenicity in young children from developing countries. Our findings are necessarily based on correlative analyses and must be further validated through epidemiological and molecular techniques.

The gut microbiota dysbiosis is linked with inflammatory bowel diseases, hypertension, atherosclerosis, hepatitis, neuropsychiatric disorders, diabetes, obesity, asthma, and development of cancer. Despite the substantial developments in oncology, cancer is still not in the category of curative diseases. However, significant steps are being taken in this direction through the identification of factors that play a role in the stages of complex carcinogenesis. Recent data obtained from human gut microbiota has shown that commensal microorganism species living on the epithelial surfaces of the intestines have an active role in this process and are also associated with personal responses to cancer treatment and toxicity. We now know more about the role of Fusobacterium nucleatum, an important member of the gut microbiota complex, as well as other microorganisms in the formation, treatment, diagnosis, and screening of colorectal cancer. In conclusion, the growing knowledge of microbiota, ...

The human gastrointestinal tract harbors an extremely complex and dynamic microbial community, including archaea, bacteria, viruses and eukaryota. This gut microbiota usually works with the host to promote health but can sometimes initiate or promote disease. Dysbiosis relationship in gut health indicating the role gut microbiota in promoting the development and progression of brain health. The human gut microbiota is a complex and dynamics microbial community that plays an important role in protecting the host against pathogenic microbes, modulating immunity and regulating metabolic processes. The insights can be elucidated with help of latest omics technology and animal model studies.

The effects of voluntary wheel-running exercise on cecal microbiota and short-chain fatty acid production were investigated in rats. The microbiota composition was notably different between the exercised and sedentary rats. Furthermore, the exercised rats showed a significantly higher n-butyrate concentration than the sedentary rats. This alteration of the cecal microbial environment may contribute to the beneficial effect of exercise on gastrointestinal disorders.

The human gut microbiome has been associated with several metabolic disorders including type 2 diabetes. Understanding metabolic changes in the gut microbiome is important to elucidate the role of gut bacteria in regulating host metabolism. Here, we used available metagenomics data from a metformin study, together with genome-scale metabolic modelling of the key bacteria in individual and community-level to investigate the mechanistic role of the gut microbiome in response to metformin. Individual modelling predicted that species that are increased after metformin treatment have higher growth rates in comparison to species that are decreased after metformin treatment. Gut microbial enrichment analysis showed prior to metformin treatment pathways related to the hypoglycemic effect were enriched. Our observations highlight how the key bacterial species after metformin treatment have commensal and competing behavior, and how their cellular metabolism changes due to different nutritional environment. Integrating different diets showed there were specific microbial alterations between different diets. These results show the importance of the nutritional environment and how the dietary guidelines may improve drug efficiency through the gut microbiota.

Background Parkinson’s disease (PD) is one of the most common neurodegenerative diseases. There is accumulating evidence that link gut microbiota to symptomatology and pathophysiology of PD. The aim of this study was to describe the pattern of gut microbiota and its association with PD and identify the effect of environmental factors on gut microbiota. This case–control study included 46 patients diagnosed as Parkinson’s disease (PD) and 31 healthy volunteers age and sex matched. Detailed history including age of onset, duration of disease, environmental risk factors, diet data, treatment, Unified Parkinson’s Disease Rating Scale (UPDRS), and gastrointestinal tract (GIT) domain of Non‐Motor Symptoms Scale (NMSS) were assessed. After extraction of bacterial DNA from the fecal samples, bacterial abundance was quantified by qPCR using 16S rRNA group-specific primers. Results Significant high abundance of Clostridium cluster IV, Akkermansia, Bifidobacterium, and lactic acid bacteria wer...

Changes in the gut microbiome have been associated with inflammatory bowel disease. A protective role of short chain fatty acids produced by the gut microbiota has been suggested as a causal mechanism. Nevertheless, multi-omic analyses have failed to identify a clear link between changes in specific taxa and disease states. Recently, metagenomic analyses unveiled that gut bacterial species have a previously unappreciated genomic diversity, implying that a geno-centric approach may be better suited to identifying the mechanisms involved. Here, we quantify the abundance of terminal genes in propionate-producing fermentative pathways in the microbiome of a large cohort of healthy subjects and patients with inflammatory bowel disease. The results show that propionate kinases responsible for propionate production in the gut are depleted in patients with Crohn’s disease. Our results also indicate that changes in overall species abundances do not necessarily correlate with changes in the a...

Non-alcoholic fatty liver disease (NAFLD) is a multifactorial disease in which environmental and genetic factors are involved. Although the molecular mechanisms involved in NAFLD onset and progression are not completely understood, the gut microbiome (GM) is thought to play a key role in the process, influencing multiple physiological functions. GM alterations in diversity and composition directly impact disease states with an inflammatory course, such as non-alcoholic steatohepatitis (NASH). However, how the GM influences liver disease susceptibility is largely unknown. Similarly, the impact of strategies targeting the GM for the treatment of NASH remains to be evaluated. This review provides a broad insight into the role of gut microbiota in NASH pathogenesis, as a diagnostic tool, and as a therapeutic target in this liver disease. We highlight the idea that the balance in metabolic fermentations can be key in maintaining liver homeostasis. We propose that an overabundance of alco...

Natural herbs and functional foods contain bioactive molecules capable of augmenting the immune system and mediating anti-viral functions. Functional foods, such as prebiotics, probiotics, and dietary fibers, have been shown to have positive effects on gut microbiota diversity and immune function. The use of functional foods has been linked to enhanced immunity, regeneration, improved cognitive function, maintenance of gut microbiota, and significant improvement in overall health. The gut microbiota plays a critical role in maintaining overall health and immune function, and disruptions to its balance have been linked to various health problems. SARS-CoV-2 infection has been shown to affect gut microbiota diversity, and the emergence of variants poses new challenges to combat the virus. SARS-CoV-2 recognizes and infects human cells through ACE2 receptors prevalent in lung and gut epithelial cells. Humans are prone to SARS-CoV-2 infection because their respiratory and gastrointestinal tracts are rich in microbial diversity and contain high levels of ACE2 and TMPRSS2. This review article explores the potential use of functional foods in mitigating the impact of SARS-CoV-2 variants on gut microbiota diversity, and the potential use of functional foods as a strategy to combat these effects.

The gut and the brain communicate bidirectionally through anatomic and humoral pathways, establishing what is known as the gut–brain axis. Therefore, interventions affecting one system will impact on the other, giving the opportunity to investigate and develop future therapeutic strategies that target both systems. Alterations in the gut–brain axis may arise as a consequence of changes in microbiota composition (dysbiosis), modifications in intestinal barrier function, impairment of enteric nervous system, unbalanced local immune response and exaggerated responses to stress, to mention a few. In this review we analyze and discuss several novel pharmacological targets within the gut–brain axis, with potential applications to improve intestinal and mental health.

Interactions between diet and gut microbiota are critical regulators of energy metabolism. The effects of fibre intake have been deeply studied but little is known about the impact of proteins. Here, we investigated the effects of high protein supplementation (Investigational Product, IP) in a double blind, randomised placebo-controled intervention study (NCT01755104) where 107 participants received the IP or an isocaloric normoproteic comparator (CP) alongside a mild caloric restriction. Gut microbiota profiles were explored in a patient subset (n = 53) using shotgun metagenomic sequencing. Visceral fat decreased in both groups (IP group: − 20.8 ± 23.2 cm2; CP group: − 14.5 ± 24.3 cm2) with a greater reduction (p < 0.05) with the IP supplementation in the Per Protocol population. Microbial diversity increased in individuals with a baseline low gene count (p < 0.05). The decrease in weight, fat mass and visceral fat mass significantly correlated with the increase in microbial ...

OBJECTIVE Obesity alters gut microbiota ecology and associates with low-grade inflammation in humans. Roux-en-Y gastric bypass (RYGB) surgery is one of the most efficient procedures for the treatment of morbid obesity resulting in drastic weight loss and improvement of metabolic and inflammatory status. We analyzed the impact of RYGB on the modifications of gut microbiota and examined links with adaptations associated with this procedure. RESEARCH DESIGN AND METHODS Gut microbiota was profiled from fecal samples by real-time quantitative PCR in 13 lean control subjects and in 30 obese individuals (with seven type 2 diabetics) explored before (M0), 3 months (M3), and 6 months (M6) after RYGB. RESULTS Four major findings are highlighted: 1) Bacteroides/Prevotella group was lower in obese subjects than in control subjects at M0 and increased at M3. It was negatively correlated with corpulence, but the correlation depended highly on caloric intake; 2) Escherichia coli species increased ...

There is increasing evidence of the health benefits of olive oil consumption in the diet. Some authors have studied the effect of high fat/high calorie diets and have detected changes on the microbiota. However, these studies are mainly based on saturated fats. Here we present a study on the specific effect on gut bacterial populations of extra virgin olive oil, rich in monounsaturated fatty acids and phenolic compounds, in comparison to refined olive oil, rich in monounsaturated fatty acids but low in phenolic compounds, and to butter, rich in saturated fatty acids and cholesterol. Four groups of animals were studied: one group of mice received a standard chow diet, and the other received three high fat diets, rich in extra virgin olive oil, refined olive oil or butter. Evolution of symbiont population in feces was studied using culture-dependent and culture-independent methods. In the latter, the V3 region of 16S rDNA was amplified and separated by denaturing gradient gel electrophoresis; followed by sequencing of the most representative bands. Culture-dependent studies and comparison of the different DGGE profiles throughout the experiment demonstrated that different dietary fats had different effects on gut microbial composition. Butter-induced changes in the microbial counts resembled those previously described in obese individuals. Interestingly, a different behavior between extra virgin and refined olive oil was also observed, extra virgin olive oil being most different from butter. To our knowledge, no studies have analyzed gut microbiota depending on diets with different fatty acid saturations including different types of olive oil. This may offer new data supporting the benefits for health of extra virgin olive oil, so important in the Mediterranean diet.

The gut microbiota is implicated in the pathogenesis of colorectal cancer (CRC). We aimed to map the CRC mucosal microbiota and metabolome and define the influence of the tumoral microbiota on oncological outcomes. Methods A multicentre, prospective observational study was conducted of CRC patients undergoing primary surgical resection in the UK (n = 74) and Czech Republic (n = 61). Analysis was performed using metataxonomics, ultra-performance liquid chromatography-mass spectrometry (UPLC-MS), targeted bacterial qPCR and tumour exome sequencing. Hierarchical clustering accounting for clinical and oncological covariates was performed to identify clusters of bacteria and metabolites linked to CRC. Cox proportional hazards regression was used to ascertain clusters associated with disease-free survival over median follow-up of 50 months. Thirteen mucosal microbiota clusters were identified, of which five were significantly different between tumour and paired normal mucosa. Cluster 7, containing the pathobionts Fusobacterium nucleatum and Granulicatella adiacens, was strongly associated with CRC (P FDR = 0.0002). Additionally, tumoral dominance of cluster 7 independently predicted favourable disease-free survival (adjusted p = 0.031). Cluster 1, containing Faecalibacterium prausnitzii and Ruminococcus gnavus, was negatively associated with cancer (P FDR = 0.0009), and abundance was independently predictive of worse disease-free survival (adjusted p = 0.0009). UPLC-MS analysis revealed two major metabolic (Met) clusters. Met 1, composed of medium chain (MCFA), long-chain (LCFA) and very long-chain (VLCFA) fatty acid species, ceramides and lysophospholipids, was negatively associated with CRC (P FDR = 2.61 × 10 -11 ); Met 2, composed of phosphatidylcholine species, nucleosides and amino acids, was strongly associated with CRC (P FDR = 1.30 × 10 -12 ), but metabolite clusters were not associated with disease-free survival (p = 0.358). An association was identified between Met 1 and DNA mismatch-repair deficiency (p = 0.005). FBXW7 mutations were only found in cancers predominant in microbiota cluster 7.

Sugarcane leaves-derived polyphenols (SLP) have been demonstrated to have diverse health-promoting benefits, but the mechanism of action has not been fully elucidated. This study aimed to investigate the anti-metabolic disease effects of SLP and the underlying mechanisms in mice. In the current study, we prepared the SLP mainly consisting of three fl avonoid glycosides, three phenol derivatives, and two lignans including one new compound, and further demonstrated that SLP reduced body weight gain and fat accumulation, improved glucose and lipid metabolism disorders, ameliorated hepatic steatosis, and regulated short-chain fatty acids (SCFAs) production and secondary bile acids metabolism in ob/ob mice. Notably, SLP largely altered the gut microbiota composition, especially enriching the commensal bacteria Akkermansia muciniphila and Bacteroides acidifaciens. Oral gavage with the above two strains ameliorated metabolic syndrome (MetS), regulated secondary bile acid metabolism, and increased the production of SCFAs in high-fat diet (HFD)-induced obese mice. These results demonstrated that SLP could be used as a prebiotic to attenuate MetS via regulating gut microbiota composition and further activating the secondary bile acids-mediated gut-adipose axis.

A polyphenolic alkaloid-enriched extract (PAE) was prepared from the fruiting bodies of a wild edible mushroom Sarcodon leucopus. Oral administration of PAE reduced hyperglycemia, hyperlipidemia, hepatic that PAE produces taxonomic and predicted functional changes in the gut microbiome of DIO mice. A of Intestinimonas and Anaerotruncus, is detected in the gut microbiome of PAE-treate mice. Accordingly, reductions of deoxycholic acid and lithocholic acid are found in the feces of PAE-treated DIO mice, which the anti-metabolic syndrome effects of the PAE is proposed. We suppose the polyphenolic alkaloid extract from S. leucopus

Gut fungi is known to play many important roles in human health regulations. Herein, we investigate the anti-obesity efficacy of the antifungal antibiotics (amphotericin B, fluconazole and 5-fluorocytosine) in the high fat diet-fed (HFD) mice. Supplementation of amphotericin B or fluconazole in water can effectively inhibit obesity and its related disorders, whereas 5-fluorocytosine exhibit little effects. The gut fungus Candida parapsilosis is identified as a key commensal fungus related to the diet-induced obesity by the culture-dependent method and the inoculation assay with C. parapsilosis in the fungi-free mice. In addition, the increase of free fatty acids in the gut due to the production of fungal lipases from C. parapsilosis is confirmed as one mechanism by which C. parapsilosis promotes obesity. The current study demonstrates the gut C. parapsilosis as a causal fungus for the development of diet-induced obesity in mice and highlights the therapeutic strategy targeting the g...

Inflammatory bowel diseases (IBD) are commonly considered as Crohn's disease and ulcerative colitis, but the possibility that the alterations in gut microbiota and oxidative stress may affect the course of experimental colitis in obese physically exercising mice treated with the intestinal alkaline phosphatase (IAP) has been little elucidated. Mice fed a high-fat-diet (HFD) or normal diet (ND) for 14 weeks were randomly assigned to exercise on spinning wheels (SW) for 7 weeks and treated with IAP followed by intrarectal administration of TNBS. The disease activity index (DAI), grip muscle strength test, oxidative stress biomarkers (MDA, SOD, GSH), DNA damage (8-OHdG), the plasma levels of cytokines IL-2, IL-6, IL-10, IL-12p70, IL-17a, TNF-α, MCP-1 and leptin were assessed, and the stool composition of the intestinal microbiota was determined by next generation sequencing (NGS). The TNBS-induced colitis was worsened in obese sedentary mice as manifested by severe colonic damage, an increase in DAI, oxidative stress biomarkers, DNA damage and decreased muscle strength. The longer running distance and weight loss was observed in mice given IAP or subjected to IAP + SW compared to sedentary ones. Less heterogeneous microbial composition was noticed in sedentary obese colitis mice and this effect disappeared in IAP + SW mice. Absence of Alistipes, lower proportion of Turicibacter, Proteobacteria and Faecalibacterium, an increase in Firmicutes and Clostridium, a decrease in oxidative stress biomarkers, 8-OHdG content and proinflammatory cytokines were observed in IAP + SW mice. IAP supplementation in combination with moderate physical activity attenuates the severity of murine colitis complicated by obesity through a mechanism involving the downregulation of the intestinal cytokine/chemokine network and oxidative stress, the modulation of the gut microbiota and an improvement of muscle strength.

Inflammatory bowel diseases (IBD) are commonly considered as Crohn’s disease and ulcerative colitis, but the possibility that the alterations in gut microbiota and oxidative stress may affect the course of experimental colitis in obese physically exercising mice treated with the intestinal alkaline phosphatase (IAP) has been little elucidated. Mice fed a high-fat-diet (HFD) or normal diet (ND) for 14 weeks were randomly assigned to exercise on spinning wheels (SW) for 7 weeks and treated with IAP followed by intrarectal administration of TNBS. The disease activity index (DAI), grip muscle strength test, oxidative stress biomarkers (MDA, SOD, GSH), DNA damage (8-OHdG), the plasma levels of cytokines IL-2, IL-6, IL-10, IL-12p70, IL-17a, TNF-α, MCP-1 and leptin were assessed, and the stool composition of the intestinal microbiota was determined by next generation sequencing (NGS). The TNBS-induced colitis was worsened in obese sedentary mice as manifested by severe colonic damage, an i...

Gut microbiota contain communities of viruses, bacteria, fungi, and Eukarya, and live as biofilms. In health, these biofilms adhere to the intestinal mucus surface without contacting the epithelium. Disruptions to the equilibrium between these biofilms and the host may create invasive pathobionts from these commensal communities and contribute to disease pathogenesis. Environmental factors appear to dominate over genetics in determining the shifts in microbiota populations and function, including when comparing microbiota between low-income and industrialized countries. The observations discussed herein carry enormous potential for the development of novel therapies targeting phenotype in microbiota dysbiosis. .

Initial establishment of the human gut microbiota is generally believed to occur immediately following birth, involving key gut commensals such as bifidobacteria that are acquired from the mother. The subsequent development of this early gut microbiota is driven and modulated by specific dietary compounds present in human milk that support selective colonization. This represents a very intriguing example of host-microbe coevolution, where both partners are believed to benefit. In recent years, various publications have focused on dissecting microbial infant gut communities and their interaction with their human host, being a determining factor in host physiology and metabolic activities. Such studies have highlighted a reduction of microbial diversity and/or an aberrant microbiota composition, sometimes referred to as dysbiosis, which may manifest itself during the early stage of life, i.e., in infants, or later stages of life. There are growing experimental data that may explain how the early human gut microbiota affects risk factors related to adult health conditions. This concept has fueled the development of various nutritional strategies, many of which are based on probiotics and/or prebiotics, to shape the infant microbiota. In this review, we will present the current state of the art regarding the infant gut microbiota and the role of key commensal microorganisms like bifidobacteria in the establishment of the first microbial communities in the human gut.

Many studies highlighted that a bidirectional communication between the gut and the central nervous system (CNS) exists. A vigorous immune response to antigens must be avoided, and pathogenic organisms crossing the gut barrier must be detected and killed. For this reason, the immune system developed fine mechanisms able to maintain this delicate balance. The microbiota is beneficial to its host, providing protection against pathogenic bacteria. It is intimately involved in numerous aspects of host physiology, from nutritional status to behavior and stress response. In the last few years, the implication of the gut microbiota and its bioactive microbiota-derived molecules in the progression of multiple diseases, as well as in the development of neurodegenerative disorders, gained increasing attention. The purpose of this review is to provide an overview of the gut microbiota with particular attention toward neurological disorders and mast cells. Relevant roles are played by the mast cells in neuroimmune communication, such as sensors and effectors of cytokines and neurotransmitters. In this context, the intake of beneficial bacterial strains as probiotics could represent a valuable therapeutic approach to adopt in combination with classical therapies. Further studies need to be performed to understand if the gut bacteria are responsible for neurological disorders or if neurological disorders influence the bacterial profile.

Many studies highlighted that a bidirectional communication between the gut and the central nervous system (CNS) exists. A vigorous immune response to antigens must be avoided, and pathogenic organisms crossing the gut barrier must be detected and killed. For this reason, the immune system developed fine mechanisms able to maintain this delicate balance. The microbiota is beneficial to its host, providing protection against pathogenic bacteria. It is intimately involved in numerous aspects of host physiology, from nutritional status to behavior and stress response. In the last few years, the implication of the gut microbiota and its bioactive microbiota-derived molecules in the progression of multiple diseases, as well as in the development of neurodegenerative disorders, gained increasing attention. The purpose of this review is to provide an overview of the gut microbiota with particular attention toward neurological disorders and mast cells. Relevant roles are played by the mast ...

The gut microbiota plays a critical role in obesity and lipid metabolism disorder. Chokeberry (Aronia melanocarpa L.) are rich in polyphenols with various physiological and pharmacological activities. We determined serum physiological parameters and fecal microbial components by using related kits, liquid chromatography-mass spectrometry (LC-MS) and 16S rRNA gene sequencing every 10 days. Real-time PCR analysis was used to measure gene expression of bile acids (BAs) and lipid metabolism in liver and adipose tissues. We analyzed the effects of different Chokeberry polyphenol (CBPs) treatment time on obesity and lipid metabolism in high fat diet (HFD)-fed rats. The results indicated that CBPs treatment prevents obesity, liver steatosis and improves dyslipidemia in HFDfed rats. CBPs modulated the composition of the gut microbiota with the extended treatment time, reducing the Firmicutes/Bacteroidetes ratio (F/B ratio) and increasing the relative abundance of Bacteroides, Prevotella, Akkermansia and other bacterial species associated with anti-obesity properties. We found that CBPs treatment gradually decreased the total BAs pool and particularly reduced the relative content of cholic acid (CA), deoxycholic acid (DCA) and enhanced the relative content of chenodeoxycholic acid (CDCA). These changes were positively correlated Bacteroides, Prevotella and negatively correlated with Clostridium, Eubacterium, Ruminococcaceae. In liver and white adipose tissues, the gene expression of lipogenesis, lipolysis and BAs metabolism were regulated after CBPs treatment in HFD-fed rats, which was most likely mediated through FXR and TGR-5 signaling pathway to improve lipid metabolism. In addition, the mRNA expression of PPARγ, UCP1 and PGC-1α were upregulated markedly in interscapular brown adipose tissue (iBAT) after CBPs treatment. We confirmed that CBPs could reduce the body weight of HFD-fed rats by accelerating energy homeostasis and thermogenesis in iBAT. Finally, the fecal microbiota transplantation (FMT) experiment results demonstrated that FMT from CBPs-treated rats failed to reduce the weight of HFD-fed rats. However, FMT from CBPs-treated rats improved dyslipidemia and reshaped gut microbiota in HFD-fed rats. In conclusion, CBPs treatment improved obesity and complications by regulating gut microbiota in HFD-fed rats. The gut microbiota plays an important role in BAs metabolism after CBPs treatment, and BAs have therefore emerged as major effectors in microbe-host signaling events that influence host lipid metabolism, energy metabolism and thermogenesis.

Serotonin (5-hydroxytryptamine or 5-HT) once most extensively studied as a neurotransmitter of the central nervous system, is seen to be predominantly secreted in the gut. About 95% of 5-HT is estimated to be found in gut mainly within the enterochromaffin cells whereas about 5% is found in the brain. 5-HT is an important enteric signaling molecule and is well known for playing a key role in sensory-motor and secretory functions in the gut. In recent times studies uncovering various new functions of gut-derived 5-HT indicate that many more are yet to be discovered in coming days. Recent studies revealed that 5-HT plays a pivotal role in immune cell activation and generation/perpetuation of inflammation in the gut. In addition to its various roles in the gut, there are now emerging evidences that suggest an important role of gut-derived 5-HT in other biological processes beyond the gut, such as bone remodeling and metabolic homeostasis. This review focuses to briefly summarize the accumulated and newly updated role of 5-HT in the maintenance of normal gut physiology and in the pathogenesis of inflammation in the gut. The collected information about this multifaceted signaling molecule may aid in distinguishing its good and bad effects which may lead to the development of novel strategies to overcome the unwanted effect, such as in inflammatory bowel disease.

Although the exact etiology of inflammatory bowel diseases (IBD) is unknown, studies have shown that dysregulated immune responses, genetic factors, gut microbiota, and environmental factors contribute to their pathogenesis. Intriguingly, serotonin (5-hydroxytryptamine or 5-HT) seems to be a molecule with increasingly strong implications in the pathogenesis of intestinal inflammation, affecting host physiology, including autophagy and immune responses, as well as microbial composition and function. 5-HT may also play a role in mediating how environmental effects impact outcomes in IBD. In this review, we aim to explore the production and important functions of 5-HT, including its impact on the gut. In addition, we highlight the bidirectional impacts of 5-HT on the immune system, the gut microbiota, and the process of autophagy and how these effects contribute to the manifestation of intestinal inflammation. We also explore recent findings connecting 5-HT signalling and the influence...

The termite gut is an efficient decomposer of polyphenol-rich diets, such as lignocellulosic biomasses, and it has been proposed that non-enzymatic oxidative mechanisms could be involved with the digestive process in these animals. However, oxidant levels are completely unknown in termites, as well as protective mechanisms against oxidative damage to the termite gut and its microbiota. As the first step in investigating the role oxidants plays in termite gut physiology, this work presents oxidant levels, antioxidant enzymatic defenses, cell renewal and microbiota abundance along the litter-feeding termite Cornitermes cumulans gut compartments (foregut, midgut, mixed segment and hindgut p1, p3, p4, and p5 segments) and salivary glands. The results show variable levels of oxidants along the C. cumulans gut, the production of antioxidant enzymes, gut cell renewal as potential defenses against oxidative injuries and the profile of microbiota distribution (being predominantly inverse to ...

Cockroaches are insects that can accommodate diets of different composition, including lignocellulosic materials. Digestion of these compounds is achieved by the insect's own enzymes and also by enzymes produced by gut symbionts. The presence of different and modular bacterial phyla on the cockroach gut tract suggests that this insect could be an interesting model to study the organization of gut bacterial communities associated with the digestion of different lignocellulosic diets. Thus, changes in the diversity of gut associated bacterial communities of insects exposed to such diets could give useful insights on how to improve hemicellulose and cellulose breakdown systems. In this work, through sequence analysis of 16S rRNA clone libraries, we compared the phylogenetic diversity and composition of gut associated bacteria in the cockroach Periplaneta americana collected in the wild-types or kept on two different diets: sugarcane bagasse and crystalline cellulose. These high fib...

Depending on their chemical structure, pectic polymers may be fermented by different bacteria in the human gut and, therefore, display a different metabolite profile. We aimed to investigate the chemical structure of pectins from peach palm fruits and to evaluate their in vitro fecal fermentation profiles. A fraction (PW-AP) containing a linear highly methyl esterified homogalacturonan (degree of esterification of 70%) with minor portions of xylogalacturonan and type I rhamnogalacturonan was submitted to fermentation by the human gut microbiota. It produced significantly less gas than fructooligosaccharides (FOS) at all evaluated time points, and in 24 h presented a cumulative gas production ~27% lower than FOS. Drops in pH could be observed during fermentation of both FOS and PW-AP. Moreover, the pectin was slower fermented than FOS, though with a similar production of total short chain fatty acids (SCFA) and a lower production of branched chain fatty acids. The amounts of specific SCFA differed from that of FOS, with higher production of acetate (16.2%) and propionate (6.2%) and lower production butyrate (112%). The ratio of total SCFA production to gas production was 4.0 mL/µmol and 5.5 mL/µmol for FOS and PW-AP, respectively, indicating that the latter leads to less gas formation per µmol of produced SCFA. Overall, the understanding of how pectic structures are fermented brings new insights into the fiber utilization by the human gut microbiota and its relation to biological outcomes.

Background: Toll-like receptor (TLR) signaling has been implicated in colorectal cancer (CRC) development. Intestinal microbiota can affect the expression of TLRs, which may induce inflammatory responses and impair the gut homeostasis. Here, we aimed to evaluate certain intestinal microbiota related to TLRs expression in colonic tissues of adenomatous polyposis and CRC patients. Results: Fecal and colonic tissue samples were collected from normal controls (NC), adenomatous (AP) cases and (CRC) patients via colonoscopy for CRC screening during 2016 to 2018. Fecal samples were collected to analyze intestinal bacteria including Streptococcus bovis , Enterococcus faecalis , Bacteroides fragilis , enterotoxigenic Bacteroides fragilis (ETBF) , Fusobacterium nucleatum , Porphyromonas gingivalis, Porphyromonas spp . and Roseburia spp . by real-time PCR. Gene expression of TLR2, TLR4 and TLR5 was examined in colonic tissues by qRT-PCR. Different abundant of gut bacteria were achieved in NC, ...

It is acknowledged that some obesity trajectories are set early in life, and that rapid weight gain in infancy is a risk factor for later development of obesity. Identifying modifiable factors associated with early rapid weight gain is a prerequisite for curtailing the growing worldwide obesity epidemic. Recently, much attention has been given to findings indicating that gut microbiota may play a role in obesity development. We aim at identifying how the development of early gut microbiota is associated with expected infant growth. We developed a novel procedure that allows for the identification of longitudinal gut microbiota patterns (corresponding to the gut ecosystem developing), which are associated with an outcome of interest, while appropriately controlling for the false discovery rate. Our method identified developmental pathways of Staphylococcus species and Escherichia coli that were associated with expected growth, and traditional methods indicated that the detection of Bacteroides species at day 30 was associated with growth. Our method should have wide future applicability for studying gut microbiota, and is particularly important for translational considerations, as it is critical to understand the timing of microbiome transitions prior to attempting to manipulate gut microbiota in early life.

It is increasingly appreciated that members of the gut microbiota are key modulators of human health and the status of major diseases including cancer, diabetes and inflammatory bowel disease. Central to their survival is the ability to metabolise complex dietary and host-derived glycans including intestinal mucins. The latter are critical components of the gut epithelium glycocalyx and mucus barriers, essential for microbiota-gut homeostasis and protection from infections by pathogens. The prominent and model human gut microbe Bacteroides thetaiotaomicron (B. theta) is a versatile and highly efficient complex glycan degrader thanks to the expansion of gene clusters termed polysaccharide utilisation loci (PULs) in its genome. While the mechanisms for several singular dietary glycan-induced PULs have been elucidated, studies on the 16-18 mucin-induced PULs in B. theta significantly lag behind. A combination of the scale and complexity of B. theta transcriptomic response to mucins and complex glycan configurations of mucins represent major hurdles for the functional characterisation of the mucin induced PULs. As a result, there is very limited knowledge on how mucin metabolism is coordinated in B. theta and what specific PULs, genes and metabolites are critical for mucin-B. theta, and more generally mucin-microbiota interactions and their importance in microbiota-gut homeostasis. Here we show that a mucin inducible PUL BT4240-50, (i) encodes activities consistent with a machinery that couples the processing of mucin-O glycan glycoproteins with the metabolism of N-acetylgalactosamine (GalNAc), an abundant mucin O-glycan sugar; (ii) is important for competitive growth on mucins invitro; (iii) encodes a key kinase enzyme (BT4240) that is critical for GalNAc metabolism and (iv) has related PULs encoded by a range of prominent Bacteroides species in the human gut. Furthermore, BT4240 kinase was also critical for glycosaminoglycan metabolism, thus extending the PULs function beyond mucins. Our work advances our understanding of the vital metabolic processes that govern mucosal glycoprotein metabolism and by implication, a key aspect of host-microbiota interactions at mucosal surfaces and highlight GalNAc as a key metabolite targeted for competitive growth.

We have identified a decreased abundance of microbial species known to have a potential antiinflammatory, protective effect in subjects that developed Celiac Disease (CeD) compared to those who did not. We aim to confirm the potential protective role of one of these species, namely Bacteroides vulgatus, and to mechanistically establish the effect of bacterial bioproducts on gluten-dependent changes on human gut epithelial functions. METHODS: We identified, isolated, cultivated, and sequenced a unique novel strain (20220303-A2) of B. vulgatus found only in control subjects. Using a human gut organoid system developed from pre-celiac patients, we monitored epithelial phenotype and innate immune cytokines at baseline, after exposure to gliadin, or gliadin plus B. vulgatus cell free supernatant (CFS). RESULTS: Following gliadin exposure, we observed increases in epithelial cell death, epithelial monolayer permeability, and secretion of pro-inflammatory cytokines. These effects were mitigated upon exposure to B. vulgatus 20220303-A2 CFS, which had matched phenotype gene product mutations. These protective effects were mediated by epigenetic reprogramming of the organoids treated with B. vulgatus CFS. CONCLUSIONS: We identified a unique strain of B. vulgatus that may exert a beneficial role by protecting CeD epithelium against a gluten-induced break of epithelial tolerance through miRNA reprogramming.

Barsak mikrobiyotası milyarlarca hücre ve mikroorganizmaya ev sahipliği yapmaktadır. Mikrobiyotanın; immün sistemin geliştirilmesi, beslenme, büyüme, barsak homeostazının sağlanması gibi önemli fonksiyonlarının olması son yıllarda araştırmacıların ilgisini çekmeye başlamış ve giderek bu konunun popülerliğini artırmıştır. Yapılan çalışmalarda barsakların organizmanın; sindirim sistemi, metabolizma, bağışıklık sistemi ve nöroendokrin uyarıcılar gibi çeşitli mekanizmalarda aktif olarak görev alan yararlı mikroorganizmaları barındırdığı ortaya konmuştur. Diğer yandan barsak mikrobiyomunun barsak mukozasında koruyucu, yapısal ve metabolik fonksiyonları vardır. Son yıllarda mikrobiyotanın egzersiz performansı üzerine olumlu etkileri olabileceği öne sürülmektedir. Henüz bunun altında yatan mekanizma tam olarak açıklanamasa da olası etkinliğin antioksidan enzim sisteminin güçlendirilmesi, yoğun egzersiz kaynaklı meydana gelen oksidatif stresin baskılanması ve kullanılan enerji sisteminin düzenlenmesi olduğu düşünülmektedir. Probiyotiklerin barsak mikrobiyotası üzerindeki iyileştirici etkileri dolaylı olarak atletik performansa olumlu katkılar sağlayabilir. Bu derleme dayanıklılık sporları ile uğraşan sporcularda probiyotik tüketiminin atletik performans üzerine etkilerini incelemek amacıyla yazılmıştır.

In this study we investigated the effects of the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene variants on the composition of faecal microbiota, in patients affected by Cystic Fibrosis (CF). CFTR mutations (F508del is the most common) lead to a decreased secretion of chloride/water, and to mucus sticky secretions, in pancreas, respiratory and gastrointestinal tracts. Intestinal manifestations are underestimated in CF, leading to ileum meconium at birth, or small bowel bacterial overgrowth in adult age. Methods: Thirty-six CF patients, fasting and under no-antibiotic treatment, were CFTR genotyped on both alleles. Faecal samples were subjected to molecular microbial profiling through Temporal Temperature Gradient Electrophoresis and species-specific PCR. Ecological parameters and multivariate algorithms were employed to find out if CFTR variants could be related to the microbiota structure. Results: Patients were classified by two different criteria: 1) presence/absence of F508del mutation; 2) disease severity in heterozygous and homozygous F508del patients. We found that homozygous-F508del and severe CF patients exhibited an enhanced dysbiotic faecal microbiota composition, even within the CF cohort itself, with higher biodiversity and evenness. We also found, by species-specific PCR, that potentially harmful species (Escherichia coli and Eubacterium biforme) were abundant in homozygous-F508del and severe CF patients, while beneficial species (Faecalibacterium prausnitzii, Bifidobacterium spp., and Eubacterium limosum) were reduced. Conclusions: This is the first report that establishes a link among CFTR variants and shifts in faecal microbiota, opening the way to studies that perceive CF as a 'systemic disease', linking the lung and the gut in a joined axis.

In liver cirrhosis (LC), impaired intestinal functions lead to dysbiosis and possible bacterial translocation (BT). Bacteria or their byproducts within the bloodstream can thus play a role in systemic inflammation and hepatic encephalopathy (HE). We combined 16S sequencing, NMR metabolomics and network analysis to describe the interrelationships of members of the microbiota in LC biopsies, faeces, peripheral/portal blood and faecal metabolites with clinical parameters. LC faeces and biopsies showed marked dysbiosis with a heightened proportion of Enterobacteriaceae. Our approach showed impaired faecal bacterial metabolism of short-chain fatty acids (SCFAs) and carbon/methane sources in LC, along with an enhanced stress-related response. Sixteen species, mainly belonging to the Proteobacteria phylum, were shared between LC peripheral and portal blood and were functionally linked to iron metabolism. Faecal Enterobacteriaceae and trimethylamine were positively correlated with blood proinflammatory cytokines, while Ruminococcaceae and SCFAs played a protective role. Within the peripheral blood and faeces, certain species (Stenotrophomonas pavanii, Methylobacterium extorquens) and metabolites (methanol, threonine) were positively related to HE. Cirrhotic patients thus harbour a 'functional dysbiosis' in the faeces and peripheral/portal blood, with specific keystone species and metabolites related to clinical markers of systemic inflammation and HE. Compositional shifts in the gut microbiota are linked with liver disease 1,2 . In liver cirrhosis (LC), the alteration in gut microbiota is characterized by an overgrowth of potentially pathogenic bacteria and a decrease in beneficial commensal species 3 . The portal system accounts for 75% of the blood reaching the hepatic parenchyma and

Rheumatoid Arthritis (RA) is a chronic systemic autoimmune disease. Modifications of gut microbiota seem to be associated with the disease, but the impact of gut microbiota on therapies’ outcome remains unclear. A role of T cells in RA pathogenesis has been addressed, particularly on the Th17/Treg cells balance. Our study aimed to evaluate in early RA (ERA) patients compared to a control group, fecal gut microbiota composition, short-chain fatty acids concentrations, and the levels of circulating Th17/Treg and their own cytokines, before and after 3 months of standard treatment (Methotrexate (MTX) plus glucocorticoids). Fecal microbiota characterization was carried out on 19 ERA patients and 20 controls matched for sex and age. Significant decreased biodiversity levels, and a partition on the base of the microbiota composition, between the ERA patients at baseline compared to controls, were observed. The co-occurrent analysis of interactions revealed a characteristic clustered struc...

This short communication reports the preliminary results of Fecal Microbial Transplantation (FMT) impact on microbiota, microbial translocation (MT), and immune activation in four recurrent Clostridium difficile infection (R-CDI) patients. After FMT a restore of gut microbiota composition with a significant increase of fecal acetyl-putrescine and spermidine and fecal acetate and butyrate, a decrease of immune activation of T cells CD4+ and CD8+levels, and of LPS binding protein (LBP) level, were observed. Preliminary results indicate that FMT seems to be helpful not only as a CDI radical cure, with an impact on fecal microbiota and metabolome profiles, but also on MT and immune activation.

In liver cirrhosis (LC), impaired intestinal functions lead to dysbiosis and possible bacterial translocation (BT). Bacteria or their byproducts within the bloodstream can thus play a role in systemic inflammation and hepatic encephalopathy (HE). We combined 16S sequencing, NMR metabolomics and network analysis to describe the interrelationships of members of the microbiota in LC biopsies, faeces, peripheral/portal blood and faecal metabolites with clinical parameters. LC faeces and biopsies showed marked dysbiosis with a heightened proportion of Enterobacteriaceae. Our approach showed impaired faecal bacterial metabolism of short-chain fatty acids (SCFAs) and carbon/methane sources in LC, along with an enhanced stress-related response. Sixteen species, mainly belonging to the Proteobacteria phylum, were shared between LC peripheral and portal blood and were functionally linked to iron metabolism. Faecal Enterobacteriaceae and trimethylamine were positively correlated with blood pro...

Liver disease is associated with qualitative and quantitative changes in the intestinal microbiota. In cirrhotic patients the alteration in gut microbiota is characterized by an overgrowth of potentially pathogenic bacteria (i.e., gram negative species) and a decrease in autochthonous familiae. Here we summarize the available literature on the risk of gut dysbiosis in liver cirrhosis and its clinical consequences. We therefore described the features of the complex interaction between gut microbiota and cirrhotic host, the so called "gut-liver axis", with a particular attention to the acquired risk of bacterial translocation, systemic inflammation and the relationship with systemic infections in the cirrhotic patient. Such knowledge might help to develop novel and innovative strategies for the prevention and therapy of gut dysbiosis and its complication in liver cirrhosis.

Introduction: Members of the human intestinal microbiota are key players in maintaining human health. Alterations in the composition of gut microbial community (dysbiosis) have been linked with important human diseases. Understanding the underlying processes that control community structure, including the bacterial interactions within the microbiota itself, is essential. Bdellovibrio bacteriovorus is a gram-negative bacterium that preys other gram-negative species for survival, acting as a population-balancer. It was found in terrestrial/aquatic ecosystems, and in animal intestines, postulating its presence also in the human gut. Methods: The present study was aimed to evaluate, by end-point PCR and qPCR, the presence of B. bacteriovorus in intestinal and faecal biopsy specimens from 92 paediatric healthy subjects and patients, suffering from Inflammatory Bowel Diseases (IBD), Celiac disease and Cystic fibrosis (CF). Results: i) B. bacteriovorus was present and abundant only in healthy individuals, while it was heavily reduced in patients, as in the case of IBD and Celiac, while in CF patients and relative controls we observed comparable results; ii) B. bacteriovorus seemed to be mucosa-associated, because all IBD and Celiac biopsies (and related controls) were treated with mucusremoving agents, leaving only the mucosa-attached microflora; iii) B. bacteriovorus abundance was district-dependent, with a major preponderance in duodenum, and gradually decreasing up to rectum; iv) B. bacteriovorus levels significantly dropped in disease status, in duodenum and ileum. Results obtained in this study could represent the first step for new therapeutic strategies aimed to restore a balance in the intestinal ecosystem, utilizing Bdellovibrio as a probiotic.