Gut Microbiota Of Healthy Individuals Research Articles

Gut microbiota in cats with inflammatory bowel disease and low-grade intestinal T-cell lymphoma.

In cats and humans, several physiological and environmental factors have been shown to alter the gut microbiota of healthy individuals. Cats share several diseases with humans such as inflammatory bowel diseases and low-grade intestinal T-cell lymphoma. The physiopathology of these chronic enteropathies is poorly understood but may involve disequilibrium of the gut microbiota composition and disruption of normal microbiome activity profiles. These disorders are increasingly diagnosed in the feline species due to improved medicalization and easier access to endoscopy in veterinary practice. This review addresses the current data on the gut microbiota of cats in health and in chronic enteropathies. Such functional analysis will help the advancement of innovative diagnostic tools and targeted therapeutic strategies.

Prolonged Intake of Luvos Healing Earth does not alter the Composition of the Gut Microbiota in Patients with Diarrhea-predominant Irritable Bowel Syndrome and Healthy Controls.

The mineral compound Luvos Healing Earth (LHE) is a commercially available remedy empirically used for a variety of gastrointestinal disorders. The aim of this study was to investigate the possible effect of prolonged LHE therapy on gut microbiota in healthy individuals and in patients with diarrhea-predominant irritable bowel syndrome (IBS-D). In this prospective exploratory study, a total of 20 participants, including 12 healthy controls and 8 patients with IBS-D, received treatment with LHE (Magenfein Granulat, 1 sachet bid) for 6 weeks. Fecal samples were collected for microbiota analysis in the morning fasting state at regular intervals at 6 different timepoints: 2 weeks before starting therapy (Screen), and every 2 weeks during LHE therapy (V0-V3). Additionally, a follow-up visit was scheduled 4 weeks after the end of treatment (V4). Microbiota analysis was performed using the GA-map® Dysbiosis Test Lx v2. Dysbiosis Index, bacterial diversity, as well as the balance or imbalance of functionally important bacteria were assessed. The microbiota analysis revealed an overlap in gut microbiota profiles between healthy controls and patients with IBS-D. Bacterial communities were consistently stable during the entire treatment period, and no significant variations in composition were observed 4 weeks after the end of the therapeutic intervention. There was a remarkable stability of microbiota profiles over time within each individual and a high inter-individual variation. The majority of fecal samples exhibited profiles, reflecting an eubiotic state, with no significant changes in dysbiosis index, functional bacteria profiles, or bacterial diversity. Our findings indicate intraindividual resilience of microbiota consortia during the entire study period. Prolonged intake of LHE does not cause significant alterations in fecal microbiota profiles in healthy controls and patients with IBS-D. Luvos Healing Earth does not affect the stability of gut microbial diversity and bacterial functions.

Effects of bathing in different hot spring types on Japanese gut microbiota

Hot springs have been used for a variety of purposes, including the treatment and amelioration of illness and recreation. Japan has ten different types of therapeutic springs (described here as spa types), which are traditionally believed to have different efficacy. However, more research must be conducted to determine how they affect healthy people. Therefore, this study focused on the gut microbiota and aimed to investigate changes in the gut microbiota in healthy people after bathing in different spa types. Using Beppu's hot springs (simple, chloride, bicarbonate, sulfur, and sulfate types), 136 healthy Japanese adults living in the Kyushu area participated in the study and bathed in the same hot spring for seven days. Fecal samples were collected before and after the 7-day bathing period, and the relative abundance of the gut microbiota was determined by 16S rRNA sequencing. The results showed that the relative abundance of Bifidobacterium bifidum increased significantly after seven consecutive days of bathing in the bicarbonate spring. Significant increases in other gut microbiota were also observed after bathing in simple, bicarbonate, and sulfur springs. These results suggest that bathing in different hot springs may affect the gut microbiota in healthy individuals differently.

Gut Microbiota Alterations and Their Functional Differences in Depression According to Enterotypes in Asian Individuals.

This study aimed to investigate alterations in the gut microbiota of patients with depression compared to those in the gut microbiota of healthy individuals based on enterotypes as a classification framework. Fecal bacteria FASTA/Q samples from 333 Chinese participants, including 107 healthy individuals (Healthy group) and 226 individuals suffering from depression (DP group), were analyzed. The participants were classified into three enterotypes: Bacteroidaceae (ET-B), Lachnospiraceae (ET-L), and Prevotellaceae (ET-P). An α-diversity analysis revealed no significant differences in microbial diversity between the Healthy and DP groups across all enterotypes. However, there were substantial differences in the gut microbial composition for β-diversity, particularly within ET-L and ET-B. The DP group within ET-B exhibited a higher abundance of Proteobacteria, while a linear discriminant analysis (LDA) of the DP group showed an increased relative abundance of specific genera, such as Mediterraneibacter, Blautia, Bifidobacterium, and Clostridium. Within ET-L, Bifidobacterium, Blautia, Clostridium, Collinsella, and Corynebacterium were significantly higher in the DP group in the LDA and ANOVA-like differential expression-2 (ALDEx2) analyses. At the species level of ET-L, Blautia luti, Blautia provencensis, Blautia glucerasea, Clostridium innocuum, Clostridium porci, and Clostridium leptum were the primary bacteria in the DP group identified using the machine learning approach. A network analysis revealed a more tightly interconnected microbial community within ET-L than within ET-B. This suggests a potentially stronger functional relationship among the gut microbiota in ET-L. The metabolic pathways related to glucose metabolism, tryptophan and tyrosine metabolism, neurotransmitter metabolism, and immune-related functions showed strong negative associations with depression, particularly within ET-L. These findings provide insights into the gut-brain axis and its role in the pathogenesis of depression, thus contributing to our understanding of the underlying mechanisms in Asian individuals. Further research is warranted to explain the mechanistic links between gut microbiota and depression and to explore their potential for use in precision medicine interventions.

The Pathogenicity of Fusobacterium nucleatum Modulated by Dietary Fibers-A Possible Missing Link between the Dietary Composition and the Risk of Colorectal Cancer.

The dietary composition has been approved to be strongly associated with the risk of colorectal cancer (CRC), one of the most serious malignancies worldwide, through regulating the gut microbiota structure, thereby influencing the homeostasis of colonic epithelial cells by producing carcinogens, i.e., ammonia or antitumor metabolites, like butyrate. Though butyrate-producing Fusobacterium nucleatum has been considered a potential tumor driver associated with chemotherapy resistance and poor prognosis in CRC, it was more frequently identified in the gut microbiota of healthy individuals rather than CRC tumor tissues. First, within the concentration range tested, the fermentation broth of F. nucleatum exhibited no significant effects on Caco-2 and NCM460 cells viability except for a notable up-regulation of the expression of TLR4 (30.70%, p < 0.0001) and Myc (47.67%, p = 0.021) and genes encoding proinflammatory cytokines including IL1B (197.57%, p < 0.0001), IL6 (1704.51%, p < 0.0001), and IL8 (897.05%, p < 0.0001) in Caco-2 cells exclusively. Although no marked effects of polydextrose or fibersol-2 on the growth of F. nucleatum, Caco-2 and NCM460 cells were observed, once culture media supplemented with polydextrose or fibersol-2, the corresponding fermentation broths of F. nucleatum significantly inhibited the growth of Caco-2 cells up to 48.90% (p = 0.0003, 72 h, 10%) and 52.96% (p = 0.0002, 72 h, 10%), respectively in a dose-dependent manner. These two kinds of fibers considerably promoted butyrate production of F. nucleatum up to 205.67% (p < 0.0001, 6% polydextrose at 24 h) and 153.46% (p = 0.0002, 6% fibersol-2 at 12 h), which explained why and how the fermentation broths of F. nucleatum cultured with fibers suppressing the growth of Caco-2 cells. Above findings indicated that dietary fiber determined F. nucleatum to be a carcinogenic or antitumor bacterium, and F. nucleatum played an important role in the association between the dietary composition, primarily the content of dietary fibers, and the risk of CRC.

Diversity and composition of gut microbiota in healthy individuals and patients at different stages of hepatitis B virus-related liver disease

BackgroundHepatitis B virus (HBV) causes chronic hepatitis B (CHB), liver cirrhosis, and hepatocellular carcinoma. The evolution of human gut microbiota during the progression of HBV-related liver diseases remains unclear. Therefore, we prospectively enrolled patients with HBV-related liver diseases and healthy individuals. Through 16S ribosomal RNA amplicon sequencing, we characterized the gut microbiota of the participants and predicted the functions of microbial communities.ResultsWe analyzed the gut microbiota of 56 healthy controls and 106 patients with HBV-related liver disease [14 with resolved HBV infection, 58 with CHB, and 34 with advanced liver disease (15 with liver cirrhosis and 19 with hepatocellular carcinoma)]. Patients with HBV-related liver disease exhibited a higher degree of bacterial richness (all P < 0.05) than did healthy controls. Beta diversity analyses revealed a distinct clustering pattern between healthy controls and patients with HBV-related liver disease (all P < 0.05). The composition of bacteria (from the phylum level to the genus level) varied across the stages of liver disease. Linear discriminant analysis effect size revealed multiple taxa that differ significantly in abundance between healthy controls and patients with HBV-related liver disease; however, fewer differences were observed among patients with resolved HBV infection, those with CHB, and those with advanced liver disease. The ratio of Firmicutes to Bacteroidetes was increased in all three patient groups compared with the ratio in healthy controls (all P < 0.001). The analysis of the sequencing data by using PICRUSt2 revealed the changes in microbial functions with disease progression.ConclusionsThe diversity and composition of gut microbiota appear to vary significantly between healthy controls and patients at different stages of HBV-related liver disease. The understanding of gut microbiota may provide novel therapeutic options in these patients.

Human gut microbiota influences drug-metabolizing enzyme hepatic Cyp3a: A human flora-associated mice study.

Several studies revealed that gut microbiota affects the hepatic drug-metabolizing enzyme cytochrome P450 (Cyp). We hypothesized that individual gut microbiota variations could contribute to CYP activity. Human flora-associated (HFA) mice are established from germ-free mice using human feces and are often used to determine the effect of the human gut microbiota on the host. This study generated two groups of HFA mice using feces from two healthy individuals. Then, the composition of gut microbiota and hepatic Cyp activity was compared to analyze the effects of gut microbiota in healthy individuals on hepatic Cyp activity. A principal coordinate analysis based on the UniFrac distance for the composition of the cecal and fecal microbiota revealed apparent differences between the recipient groups. Hepatic Cyp, which is a marked difference in Cyp3a activity and Cyp3a11 gene expression, was observed between the recipient groups. Cyp2c and Cyp1a activities did not differ between recipient groups, with significantly lower enzymatic activities in recipients than in germ-free mice. These results indicate that the human gut microbiota affects hepatic Cyp activity. Especially, human gut microbiota composition differences have a pronounced effect on Cyp3a activity via Cyp3a11 gene expression regulation. Therefore, human gut microbiota variations among individuals may affect numerous drug metabolism, leading to drug efficacy and toxicity.

Human gut microbiota stimulate defined innate immune responses that vary from phylum to strain

The potential of commensal bacteria to modulate host immunity remains largely uncharacterized, largely due to the vast number of strains that comprise the human gut microbiota. We have developed a screening platform to measure the innate immune responses of myeloid cells to 277 bacterial strains isolated from the gut microbiota of healthy individuals and those with inflammatory bowel diseases. The innate immune responses to gut-derived bacteria are as strong as those toward pathogenic bacteria, and they vary from phylum to strain. Myeloid cells differentially rely upon innate receptors TLR2 or TLR4 to sense taxa, with differential sensing of Bacteroidetes and Proteobacteria that predict invivo functions. These innate immune responses can be modeled using combinations of up to 8 Toll-like receptor (TLR) agonists. Furthermore, the immunogenicity of strains is stable over time and following fecal microbiota transplantation into new human recipients. Collectively, this high-throughput approach provides an insight into how commensal microorganisms shape innate immune phenotypes.

Physical activity induced alterations of gut microbiota in humans: a systematic review

BackgroundGut microbiota is considered to have a great impact on human health and disease. While it is widely recognized that the gut microbiota of healthy individuals differs from those with obesity, inflammatory bowel disease, metabolic syndrome, and other chronic diseases, the alterations of gut microbiota with physical activity are not fully understood. Accordingly, we performed this systematic review to address the question regarding the effects of mild and intense exercise on the gut microbiota in humans.MethodsThe comparative analyses of gut microbiota were conducted following the PRISMA protocol to determine the differences in the active vs. non-active individuals (phenotypes) (n = 11), including the influence of physical activity intervention on the human gut microbiota (n = 13); the differences in the gut microbiota of athletes vs. non-athletes (n = 8); and the microbiota status at different stages of athletic performance or intervention (n = 7), with various of physical activities, sport disciplines, and activity duration. Literature searches were completed using four databases: PubMed, Web of Science, Scopus, and EBSCO, and 2090 articles were retrieved by using appropriate keywords. The low heterogeneity of the studies hasn’t allowed us to prepare a meta-analysis. After excluding 2052 articles, we ultimately selected 38 articles that met the eligibility criteria for this review.ResultsThe data analyses revealed that in non-athletes rising physical activity markedly influenced the relative abundance of short-chain fatty acid (SCFA). Aerobic training that lasted 60 min, and physical activity that characterized 60% HRmax or more also influenced beta diversity indexes. The results showed that athletes harbor a more diverse type of intestinal microflora than non-athletes, but with a relatively reduced abundance of SCFA- and lactic acid-producing bacteria, thereby suggesting an adverse effect of intense exercise on the population of gut microbiota.ConclusionIt is concluded that the level of physical activity modulates the gastrointestinal microbiota in humans. For a long period, increasing the intensity and volume of exercise may lead to gut dysbiosis. Perhaps, proper supplementation should be considered to keep gut microbiota in large biodiversity and richness, especially under unfavorable gut conditions associated with intense exercise.Trial registrationProspero CRD42021264064.

Changes in gut microbiota composition with age and correlations with gut inflammation in rats.

Increasing evidences indicate that gut microbiota composition is associated with multiple inflammatory diseases. However, little is known about how gut microbiota changes with age and correlations with gut inflammation at sexual maturity stage of healthy individuals. Elucidating the dynamic changes of gut microbiota in healthy individuals at the sexual maturity stage and correlations with gut inflammation can provide clues for early risk assessment of gut diseases at the sexual maturity stage. Here, the shift in gut bacteria and its relationship with gut inflammation at the sexual maturity stage were explored. Sprague–Dawley rats at the sexual maturity stage were used in this study. 16S rRNA gene sequencing was performed to decipher gut bacteria shifts from the 7th week to the 9th week, and enzyme-linked immunosorbent assay (ELISA) was used to measure gut inflammation and gut barrier permeability. We found an increase in bacterial richness with age and a decrease in bacterial diversity with age. The gut bacteria were primarily dominated by the phyla Firmicutes and Bacteroides and the genus Prevotella. The relative abundance of Firmicutes increased with age, and the relative abundance of Bacteroides decreased with age. There was a positive correlation between body weight and the Firmicutes:Bacteroides ratio. More and more gut microbiota participated in the host gut inflammation and barrier permeability regulation with age. Ruminococcus was the only gut bacteria participated in gut inflammation and barrier permeability regulation both in the 7th week and the 15th week. These results provide a better understanding of the relationship between gut bacteria and gut inflammation in sexually mature rats and show that Ruminococcus may be a potential indicator for early risk assessment of gut inflammation.

The Role of the Gut Microbiota in the Pathogenesis of Diabetes.

Diabetes mellitus is a significant clinical and therapeutic problem because it can lead to serious long-term complications. Its pathogenesis is not fully understood, but there are indications that dysbiosis can play a role in the development of diabetes, or that it appears during the course of the disease. Changes in microbiota composition are observed in both type 1 diabetes (T1D) and type 2 diabetes (T2D) patients. These modifications are associated with pro-inflammation, increased intestinal permeability, endotoxemia, impaired β-cell function and development of insulin resistance. This review summarizes the role of the gut microbiota in healthy individuals and the changes in bacterial composition that can be associated with T1D or T2D. It also presents new developments in diabetes therapy based on influencing the gut microbiota as a promising method to alter the course of diabetes. Moreover, it highlights the lacking data and suggests future directions needed to prove the causal relationship between dysbiosis and diabetes, both T1D and T2D.

Cell-Free Supernatant of Odoribacter splanchnicus Isolated From Human Feces Exhibits Anti-colorectal Cancer Activity.

The gut microbiota (GM) has been shown to be closely associated with the development of colorectal cancer (CRC). However, the involvement of GM is CRC has mainly been demonstrated by metagenomic profiling studies showing the compositional difference between the GM of healthy individuals and that of CRC patients and not by directly studying isolated gut microbes. Thus, to discover novel gut microbes involved in CRC, we isolated the GM from the feces of healthy individuals and evaluated its anti-CRC activity in vitro and in vivo. After GM isolation, cell-free supernatants (CFSs) were prepared from the isolated gut microorganisms to efficiently screen a large amount of the GM for anti-proliferative ability in vitro. Our results showed that the CFSs of 21 GM isolates had anti-proliferative activity against human colon cancer HCT 116 cells. Of these 21 GM isolates, GM07 was chosen for additional study because it had the highest anti-cancer activity against mouse colon cancer CT 26 cells in vitro and was further evaluated in a CT 26 allograft mouse model in vivo. GM07 was identified as Odoribacter splanchnicus through phylogenetic analysis based on 16S rRNA gene sequencing. Further investigation determined that the CFS of O. splanchnicus (OsCFS) induced anti-proliferative activity via apoptosis, but not cell cycle arrest. Moreover, GC/MS analysis suggested that the putative active molecule in OsCFS is malic acid. Finally, in the CRC mouse model, peri-tumoral injection of OsCFS significantly decreased CRC formation, compared to the control group. Altogether, these findings will provide valuable information for the discovery of potential probiotic candidates that inhibit CRC.

Gut and Cutaneous Microbiome Featuring Abundance of Lactobacillus reuteri Protected Against Psoriasis-Like Inflammation in Mice.

BackgroundPsoriasis is a chronic autoinflammatory skin disease, and its aetiology remains incompletely understood. Recently, gut microbial dysbiosis is found to be tightly associated with psoriasis.ObjectiveWe sought to reveal the causal role of gut microbiota dysbiosis in psoriasis pathogenesis and investigate the protective effect of healthy commensal bacteria against imiquimod -induced psoriasis-like skin response.MethodsBy using fecal microbial transplantation (FMT), 16S rRNA gene-based taxonomic profiling and Lactobacillus supplement, we have assessed the effect of FMT from healthy individuals on psoriasis-like skin inflammation and associated immune disorders in imiquimod-induced psoriasis mice.ResultsHere, by using psoriasis mice humanized with the stools from healthy donors and psoriasis patients, the imiquimod-induced psoriasis in mice with psoriasis patient stool was found to be significantly aggravated as compared to the mice with healthy donor stools. Further analysis showed fecal microbiota of healthy individuals protected against Treg/Th17 imbalance in psoriasis. Moreover, we found the gut and skin microbiome in mice receipted with gut microbiota of healthy individuals (HD) differed from those of mice receipted with gut microbiota of psoriasis patients (PSD). 16S rRNA sequencing revealed that Lactobacillus reuteri was greatly enriched in fecal and cutaneous microbiome of HD mice as compared to PSD mice. Intriguingly, supplement with Lactobacillus reuteri was sufficient to increase the expression of anti-inflammatory gene IL-10, reduce Th17 cells counts and confer resistance to imiquimod-induced inflammation on the mice with gut microbiota dysbiosis.ConclusionOur results suggested that the gut microbiota dysbiosis is the potential causal factor for psoriasis and the gut microbiota may serve as promising therapy target for psoriasis patients.

Dietary Variety Relates to Gut Microbiota Diversity and Abundance

ObjectivesCumulative evidence indicated dietary intake is associated with gut microbiota. This study aim to investigate the association between Dietary Variety Score (DVS) and the Index of Nutritional Quality (INQ) and gut microbiota in healthy individuals. MethodsIn this cross-sectional study, we analyzed gut microbiota composition and structure using 16S rRNA gene (V4-V5 region) sequencing of 128 participants. Dietary frequency and 24-h dietary consumption was ascertained using an FFQ. Differences in α- and β-diversity and taxonomic relative abundances between the higher and lower DVS and INQs were compared, followed by multivariable analyses. ResultsThe structure of the microbiota significantly differed by dietary variety. A lower score for DVS was associated with significantly lower richness (Shannon index P = 0.0096). The INQ of vitamin E (INQVE), Zinc (INQZn) and vitamin B6 (INQB6) correlated positively with the Shannon index (rho = 0.235, P = 0.008 for INQVE; rho = 0.209, P = 0.019 for INQZn; rho = 0.182, P = 0.040 for INQB6). A cumulative higher score of INQZn, INQB6 and INQVE was associated with significantly higher richness (Shannon index p-trend = 0.001). A lower score for DVS was associated with significantly reduced relative abundance of genus on Alistipes, Megasphaera and Barnesiella but higher Roseburia and Haemophilus. A lower score for INQVE was associated with significantly reduced relative abundance of genus on Coprococcus and Romboutsia. A lower score for INQB6 was associated with significantly reduced relative abundance of genus on Lachnospira, Dorea, Butyricicoccus, and Anaerostipes but higher Lachnoclostridium (the linear discriminant analysis effect size (LEfSe) >3). Meanwhile, the abundance of Coprococcus significantly increased with the higher cumulative score of INQVE, INQZn and INQB6 (P < 0.01), and it associated negatively with LDL level (coef = –0.264, P = 0.041). The findings were confirmed by multivariate analysis. ConclusionsLower dietary variety was significantly associated with reduced relative abundance of potentially beneficial bacteria but increased potentially harmful bacteria in the healthy individuals. Funding SourcesThis work was supported by the National Natural Science Foundation of China (No.82,060,593), Natural Science Foundation of Guangxi Province (No. 2018GXNSFDA050019).

Microbiota Features Associated With a High-Fat/Low-Fiber Diet in Healthy Adults.

A high intake of dietary saturated fatty acids (SFAs) is related to an increased risk of obesity, inflammation and cancer-related diseases, and this risk is attenuated only when SFAs are replaced by unsaturated fats and unrefined carbohydrates. The gut microbiota has recently emerged as a new environmental factor in the pathophysiology of these disorders, and is also one of the factors most influenced by diet. We sought to determine whether the gut microbiota of healthy individuals whose intake of SFAs exceeds World Health Organization (WHO) recommendations exhibits features similar to those reported in people with obesity, inflammation, cancer or metabolic disease. Healthy non-obese subjects were divided into two groups based on their SFAs intake. Body composition and gut microbiota composition were analyzed, and associations between bacterial taxa, diet and body fat composition were determined globally and separately by sex. Metagenome functional pathways were predicted by PICRUSt analysis. Subjects whose SFAs intake exceeded WHO recommendations also had a dietary pattern of low fiber intake. This high saturated fat/low fiber diet was associated with a greater sequence abundance of the Anaerotruncus genus, a butyrate producer associated with obesity. Analysis of data of high SFAs intake by sex showed that females presented with a greater abundance of Campylobacter, Blautia, Flavonifractor and Erysipelatoclostridium, whereas males showed higher levels of Anaerotruncus, Eisenbergiella, a genus from the order Clostridiales (FamilyXIIIUCG_001) and two genera from the Lachnospiraceae family. PICRUSt analysis confirmed these data, showing a correlation with a decrease in the abundance of sequences encoding for transporters of some metals such as iron, which is needed to maintain a healthy metabolism. Thus, the microbiota of healthy people on a high SFAs diet contain bacterial taxa (Anaerotruncus, Lachnospiraceae Flavonifractor, Campylobacter, Erysipelotrichacea and Eisenbergiella) that could be related to the development of some diseases, especially obesity and other pro-inflammatory diseases in women. In summary, the present study identifies bacterial taxa that could be considered as early predictors for the onset of different diseases in healthy subjects. Also, sex differences in gut microbiota suggest that women and men differentially benefit from following a specific diet.

Emergence of tigecycline- and eravacycline-resistant Tet(X4)-producing Enterobacteriaceae in the gut microbiota of healthy Singaporeans.

The recently discovered tigecycline-inactivating enzyme Tet(X4) can confer high-level tigecycline resistance on its hosts, which makes it a public health concern. This study focused on isolation and screening of Tet(X4)-positive Enterobacteriaceae from the gut microbiota of a cohort of healthy individuals in Singapore. MinION and Illumina sequencing was performed to obtain the complete genome sequences of Escherichia coli 2EC1-1 and 94EC. Subsequently, 109 human faecal samples were screened retrospectively for eravacycline-resistant Enterobacteriaceae strains, which were further tested for tet(X4) by PCR. The taxonomy of the isolated strains was determined by 16S rRNA gene PCR and Sanger sequencing. Comparative genomic analysis of E. coli 2EC1-1 and 94EC revealed that both carry tet(X4), which is encoded by IncI1-type plasmids p2EC1-1 and p94EC-2, respectively. Retrospective screening of faecal samples collected from 109 healthy individuals showed that the faecal carriage rate of Tet(X4)-producing Enterobacteriaceae is 10.1% (95% CI = 5.1%-17.3%), suggesting that tet(X4) is widely distributed in the gut microbiota of healthy individuals in Singapore. To the best of our knowledge, this is the first report on the prevalence of tet(X4) in the gut microbiota of a healthy human cohort, as well as the first description of this resistance mechanism outside of China. Our findings suggest that surveillance of tet(X4) in community settings is vital to monitor the spread of this resistance mechanism.

Black tea benefits short-chain fatty acid producers but inhibits genus Lactobacillus in the gut of healthy Sprague-Dawley rats.

The gut microbiota plays important roles in physiological and pathological processes of the host. The effect of black tea on the gut microbiota of healthy individuals remains unclear. Healthy Sprague-Dawley (SD) rats were given black tea for 4 weeks, and cecum content, serum, intestinal, and hepatic samples were collected. The results showed that black tea increased α-diversity and modulated β-diversity of the gut microbiota. Additionally, black tea enriched several short-chain fatty acid (SCFA) producers but suppressed genus Lactobacillus. Further tests revealed that the enrichment of SCFA producers was associated with a decrease in the oxidative stress of cecum content caused by black tea, and related to increased luminal butyric acid levels and enhanced intestinal barrier function. The suppression of genus Lactobacillus was related to the increase in luminal total bile acids caused by black tea. In vitro tests showed that bile acids rather than black tea directly inhibited Lactobacillus strains. The reduction in genus Lactobacillus did not affect the effects of black tea on intestinal barrier function and lipid levels. Our results imply that the effects of black tea on gut microbiota in healthy individuals are complex and provide a new perspective on the associations among black tea, gut microbiota, and health. © 2020 Society of Chemical Industry.

Extracellular Matrix and Oxidative Phosphorylation: Important Role in the Regulation of Hypothalamic Function by Gut Microbiota.

BackgroundIn previous studies, our team examined the gut microbiota of healthy individuals and depressed patients using fecal microbiota transplantation of germ-free (GF) mice. Our results showed that depression-like and anxiety-like behavioral phenotypes of host mice were increased, but the molecular mechanism by which gut microbiota regulate host behavioral phenotypes is still unclear.MethodsTo investigate the molecular mechanism by which gut microbiota regulate host brain function, adult GF mice were colonized with fecal samples derived from healthy control (HC) individuals or patients with major depressive disorder (MDD). Transcriptomic profiling of hypothalamus samples was performed to detect differentially expressed genes (DEGs). qRT-PCR was used for validation experiments.ResultsColonization germ-free (CGF) mice had 243 DEGs compared with GF mice. The most enriched KEGG pathways associated with upregulated genes were “protein digestion and absorption,” “extracellular matrix (ECM)-receptor interaction,” and “focal adhesion.” MDD mice had 642 DEGs compared with HC mice. The most enriched KEGG pathways associated with upregulated genes in MDD mice were also “protein digestion and absorption,” “ECM-receptor interaction,” and “focal adhesion.” Meanwhile, the most enriched KEGG pathway associated with downregulated genes in these mice was “oxidative phosphorylation,” and genes related to this pathway were found to be highly correlated in PPI network analysis.ConclusionIn summary, our findings suggested that regulation of ECM is a key mechanism shared by different gut microbiota and that inhibition of energy metabolism in the hypothalamus by gut microbiota derived from MDD patients is a potential mechanism of behavioral regulation and depression.

Isoflavone Rich Diet Ameliorates Experimental Autoimmune Encephalomyelitis (EAE) through Modulation of Gut Bacteria Depleted in Multiple Sclerosis Patients

Abstract Multiple sclerosis (MS), an autoimmune disease of the central nervous system, has been shown to be influenced by gut bacteria. We and others have shown that MS patients have depletion of isoflavone-metabolizing bacteria compared to healthy individuals. We hypothesize that gut bacteria-mediated isoflavone metabolism induces an anti-inflammatory state and reduction/depletion of these gut bacteria might predispose to MS development and/or severity. To test this, we placed mice on a diet with or without isoflavones and induced EAE, an animal model of MS. Mice on an isoflavone diet developed milder disease compared to those on an isoflavone-free diet. This phenomenon was dependent on the presence of isoflavone-metabolizing gut bacteria as confirmed by antibiotic depletion and bacterial reconstitution. Mice on an isoflavone diet exhibited altered peripheral immune responses, CNS cellular infiltration, and CNS pathology post EAE induction compared to mice on an isoflavone-free diet. Additionally, the gut microbiome of mice on an isoflavone diet and an isoflavone-free diet closely resembles the gut microbiota of healthy individuals and MS patients, respectively. Thus our results suggest that dietary isoflavone metabolites produced with the help of gut bacteria can influence the disease through modulation of the immune system.

Time-restricted feeding is associated with changes in human gut microbiota related to nutrient intake.

Time-restricted feeding (TRF) is a dietary therapeutic remedy for the prevention and treatment of metabolic diseases. Gut microbiota may influence the host metabolism and nutritional status of individuals. Given the significance of TRF and gut microbiota in metabolic diseases, the aim of this study was to explore the association between TRF and gut microbiota in healthy individuals, which is not clearly elucidated. Thirty healthy men (18-30 y of age) were divided in to two groups (TRF: n = 15 and non-TRF: n = 15). The TRF group was instructed to not consume any food for 16 h/d. Two-day food diary was used for dietary data collection. Stool samples were collected from both groups after 25 d of TRF or non-TRF. Gut microbiota profile was analyzed and quantified by using 16S rRNA gene sequencing. Cluster analysis revealed that Prevotlla_9, Faecalibacterium, and Dialister were the most abundant species in TRF, whereas Prevotell_7, Alloprevotella, and Prevotella_2 were less abundant in the non-TRF group. At the genus level, gut microbiota of the TRF group was significantly changed compared with that of the non-TRF group. Moreover, bar plot analysis revealed that Bacteroidetes was the most abundant phylum in TRF group, followed by Firmicutes. Heat map correlation showed that polyunsaturated fatty acids and vitamin D were positively correlated with Firmicutes, whereas iodine, vitamin E, magnesium, and carbohydrate intake were negative correlated with microbial richness. The present study demonstrated that TRF is associated with microbial composition and relative abundance. TRF intervention might increase microbial abundance, thereby influencing the host metabolism and nutritional status.