Gut Microbiota-host Interactions Research Articles

Biocontrol of Avian Gastrointestinal Parasites Using Predatory Fungi: Current Status, Challenges, and Opportunities

This review describes the current research status regarding the implementation of predatory fungi in the biological control approach of bird gastrointestinal (GI) parasitosis. The main GI parasites of Galliformes (e.g., broilers, layers, peacocks, pheasants) and Ratites (e.g., ostriches, emus, rheas) are addressed, as well as their impact on farms, zoos, and private collections. The main characteristics regarding biocontrol with predatory fungi are briefly described, such as their mode of action and efficacy against GI parasites of different animal hosts. The state of the art regarding the use of predatory fungi in birds is reviewed here by describing all associated articles already published in the main databases, techniques, and their main findings. Ovicidal fungi such as Pochonia chlamydosporia, Metarhizium spp. and Acremonium spp., and larvicidal fungi, namely Duddingtonia flagrans, Arthrobotrys spp. and Monacrosporium thaumasium, have shown promising predacious activity against ascarid eggs and nematode larvae from chickens and ostriches, both in vitro and in vivo, also revealing tolerance to the GI passage in chickens and maintenance of predacious capacity. Further studies are needed to understand the fungi–parasite–host gut microbiota interactions and target other avian GI parasitic species, such as nematodes, coccidia, cestodes, and trematodes.

Fusobacterium nucleatum promotes colorectal cancer cells adhesion to endothelial cells and facilitates extravasation and metastasis by inducing ALPK1/NF-κB/ICAM1 axis

ABSTRACT Metastasis is the leading cause of death for colorectal cancer (CRC) patients, and the spreading tumor cells adhesion to endothelial cells is a critical step for extravasation and further distant metastasis. Previous studies have documented the important roles of gut microbiota-host interactions in the CRC malignancy, and Fusobacterium nucleatum (F. nucleatum) was reported to increase proliferation and invasive activities of CRC cells. However, the potential functions and underlying mechanisms of F. nucleatum in the interactions between CRC cells and endothelial cells and subsequent extravasation remain unclear. Here, we uncovered that F. nucleatum enhanced the adhesion of CRC cells to endothelial cells, promoted extravasation and metastasis by inducing ICAM1 expression. Mechanistically, we identified that F. nucleatum induced a new pattern recognition receptor ALPK1 to activate NF-κB pathway, resulting in the upregulation of ICAM1. Interestingly, the abundance of F. nucleatum in tumor tissues of CRC patients was positively associated with the expression levels of ALPK1 and ICAM1. Moreover, high expression of ALPK1 or ICAM1 was significantly associated with a shorter overall survival time of CRC patients. This study provides a new insight into the role of gut microbiota in engaging into the distant metastasis of CRC cells.

Gut microbiome alterations and gut barrier dysfunction are associated with host immune homeostasis in COVID-19 patients

BackgroundCOVID-19 is an infectious disease characterized by multiple respiratory and extrapulmonary manifestations, including gastrointestinal symptoms. Although recent studies have linked gut microbiota to infectious diseases such as influenza, little is known about the role of the gut microbiota in COVID-19 pathophysiology.MethodsTo better understand the host-gut microbiota interactions in COVID-19, we characterized the gut microbial community and gut barrier function using metagenomic and metaproteomic approaches in 63 COVID-19 patients and 8 non-infected controls. Both immunohematological parameters and transcriptional profiles were measured to reflect the immune response in COVID-19 patients.ResultsAltered gut microbial composition was observed in COVID-19 patients, which was characterized by decreased commensal species and increased opportunistic pathogenic species. Severe illness was associated with higher abundance of four microbial species (i.e., Burkholderia contaminans, Bacteroides nordii, Bifidobacterium longum, and Blautia sp. CAG 257), six microbial pathways (e.g., glycolysis and fermentation), and 10 virulence genes. These severity-related microbial features were further associated with host immune response. For example, the abundance of Bu. contaminans was associated with higher levels of inflammation biomarkers and lower levels of immune cells. Furthermore, human-origin proteins identified from both blood and fecal samples suggested gut barrier dysfunction in COVID-19 patients. The circulating levels of lipopolysaccharide-binding protein increased in patients with severe illness and were associated with circulating inflammation biomarkers and immune cells. Besides, proteins of disease-related bacteria (e.g., B. longum) were detectable in blood samples from patients.ConclusionsOur results suggest that the dysbiosis of the gut microbiome and the dysfunction of the gut barrier might play a role in the pathophysiology of COVID-19 by affecting host immune homeostasis.

Preparing and Rearing Axenic Insects with Tissue Cultured Seedlings for Host-Gut Microbiota Interaction Studies of the Leaf Beetle.

Insect guts are colonized by diverse bacteria that can profoundly impact the host's physiological traits. Introducing a particular bacterial strain into an axenic insect is a powerful method to verify gut microbial function and elucidate the mechanisms underlying gut microbe-host interactions. Administering antibiotics or sterilizing egg surfaces are two commonly used methods to remove gut bacteria from insects. However, in addition to the potential adverse effects of antibiotics on insects, previous studies indicated that feeding antibiotics could not eliminate gut bacteria. Thus, germ-free artificial diets are generally employed to maintain axenic insects, which is a tedious and labor-intensive process that cannot fully resemble nutritional components in natural food. Described here is an efficient and simple protocol to prepare and maintain axenic larvae of a leaf beetle(Plagiodera versicolora). Specifically, surfaces of the beetle eggs were sterilized, following which germ-free poplar leaves were used to rear axenic larvae. The axenic status of the insects was further confirmed via culture-dependent and culture-independent assays. Collectively, by combining egg disinfection and germ-free cultivation, an efficient and convenient method was developed to obtain axenic P. versicolora, providing a readily transferable tool for other leaf-eating insects.

Preparing and Rearing Axenic Insects with Tissue Cultured Seedlings for Host-Gut Microbiota Interaction Studies of the Leaf Beetle

Preparing and Rearing Axenic Insects with Tissue Cultured Seedlings for Host-Gut Microbiota Interaction Studies of the Leaf Beetle

Emerging Applications of Metabolomics to Assess the Efficacy of Traditional Chinese Medicines for Treating Type 2 Diabetes Mellitus

Diabetes is a common and complex disease that can exacerbate the complications related to cardiovascular disease, and this is especially true for type 2 diabetes mellitus (T2DM). In addition to the standard pharmacological therapies, T2DM has also been treated with nonconventional regimens such as traditional Chinese medicine (TCM), e.g., herbal medicines and TCM prescriptions, although the mechanisms underlying the therapeutic benefits remain unclear. In this regard, many studies have used metabolomics technology to elucidate the basis for the efficacy of TCM for T2DM. Metabolomics has recently attracted much attention with regard to drug discovery and pharmacologically relevant natural products. In this review, we summarize the application of metabolomics to the assessment of TCM efficacy for treating T2DM. Increasing evidence suggests that the metabolic profile of an individual patient may reflect a specific type of T2DM syndrome, which may provide a new perspective for disease diagnosis. In addition, TCM has proved effective for countering the metabolic disorders related to T2DM, and this may constitute the basis for TCM efficacy. Therefore, further determining how TCM contributes to the reversal of metabolic disorders, such as using network pharmacology or by assessing the contribution of host–gut microbiota interactions, will also provide researchers with new potential targets for pharmacologic-based therapies.

Cytotoxic T-Cell Trafficking Chemokine Profiles Correlate With Defined Mucosal Microbial Communities in Colorectal Cancer.

The involvement of gut microbiota in T-cell trafficking into tumor tissue of colorectal cancer (CRC) remains to be further elucidated. The current study aimed to evaluate the expression of major cytotoxic T-cell trafficking chemokines (CTTCs) and chemokine-associated microbiota profiles in both tumor and adjacent normal tissues during CRC progression. We analyzed the expression of chemokine C-X-C motif ligands 9, 10, and 11 (CXCL9, CXCL10, and CXCL11), and C-C motif ligand 5 (CCL5), characterized gut mucosa-associated microbiota (MAM), and investigated their correlations in CRC patients. Our results showed that the expression of CXCL9, CXCL10, and CXCL11 was significantly higher in tumor than in adjacent normal tissues in 136 CRC patients. Notably, the high expression of CXCL9 in tumor tissues was associated with enhanced CD8+ T-cell infiltration and improved survival. Moreover, the MAM in tumor tissues showed reduction of microbial diversity and increase of oral bacteria. Microbial network analysis identified differences in microbial composition and structure between tumor and adjacent normal tissues. In addition, stronger associations between oral bacteria and other gut microbes were observed. Furthermore, the correlation analysis between the defined MAM and individual CTTCs showed that the CTTCs’ correlated operational taxonomic units (OTUs) in tumor and adjacent normal tissues rarely overlap with each other. Notably, all the enriched OTUs were positively correlated with the CTTCs in either tumor or adjacent normal tissues. Our findings demonstrated stronger interactions between oral bacteria and gut microbes, and a shifted correlation pattern between MAM and major CTTCs in tumor tissues, underlining possible mechanisms of gut microbiota–host interaction in CRC.

The First Report of Bacteroides fragilis and Bacteroides thetaiotaomicron Relative Abundance in Obese Iranian Population

Background: Obesity is a multifactorial disorder, and gut microbiota has a fundamental role in its pathophysiology. Bacteroides spp. has significant roles in gut microbiota- host interactions that determine health and disease development. Since the gut microbiota pattern changes based on different criteria in each population, we studied the abundance of two important Bacteroides strains, Bacteroides fragilis, and Bacteroides thetaiotaomicron, in Iranian obese and normal-weight subjects for the first time. Methods: In this study, 100 participants were recruited and classified based on their body mass index (BMI). The subjects were divided into normal (average BMI, 22.37 kg/m2) and obese (average BMI, 29.10 kg/m2) groups. Bacterial DNA was extracted from the samples, and quantitative polymerase chain reaction (qPCR) was conducted based on 16s rDNA universal primers. Finally, the correlation between bacterial abundance and obesity was investigated. Results: The results of qPCR showed that the relative abundance means of B. fragilis in normal weight and obese subjects was 8.68 × 1012 and 9.27 × 1012 cfu/mL, respectively. Also, the relative abundance mean of B. thetaiotaomicron in normal weight and obese subjects was 2.32 × 1012 and 5.39 × 1012 cfu/mL, respectively. Although obese subjects had more B. fragilis and B. thetaiotaomicron abundance compared to subjects with normal weight, no significant difference was identified between relative abundance of B. fragilis (P = 0.79) and B. thetaiotaomicron (P = 0.18) in the two groups. Conclusions: Although obese subjects had more B. fragilis and B. thetaiotaomicron abundance compared to normal-weight subjects, no significant difference was identified between the two groups. Since Bacteroides spp. have significant role in gut microbiota-host interaction, determination of their abundance in obesity development and targeting restoration of gut microbiota pattern could be valuable in controlling obesity. In this regard, dietary intervention could be based on determination of gut microbiota pattern in certain populations.

Microbiota Metabolites Modulate the T Helper 17 to Regulatory T Cell (Th17/Treg) Imbalance Promoting Resilience to Stress-Induced Anxiety- and Depressive-Like Behaviors

ObjectivesChronic stress disrupts immune homeostasis while gut microbiota-derived metabolites attenuate inflammation, thus promoting resilience to stress-induced immune and behavioral abnormalities. There are both peripheral and brain region-specific maladaptations of the immune response to chronic stress that produce interrelated mechanistic considerations required for the design of novel therapeutic strategies for prevention of stress-induced psychological impairment. MethodsPharmacokinetic studies revealed that this effect may be attributed to specific synbiotic-produced metabolites including 4-hydroxyphenylpropionic, 4-hydroxyphenylacetic acid and caffeic acid. Using a model of chronic unpredictable stress, behavioral abnormalities were associated to strong immune cell activation and recruitment in the ileum while inflammasome pathways were implicated in the prefrontal cortex and hippocampus. Chronic stress also upregulated the ratio of activated proinflammatory T helper 17 (Th17) to regulatory T cells (Treg) in the liver and ileum and it was predicted with ingenuity pathway analysis that the aryl hydrocarbon receptor (AHR) could be driving the synbiotic’s effect on the ileum’s inflammatory response to stress. Synbiotic treatment indiscriminately attenuated the stress-induced immune and behavioral aberrations in both the ileum and the brain while in a gut-immune co-culture model, the synbiotic-specific metabolites promoted anti-inflammatory activity through the AHR. ResultsThis study shows that a combination of probiotics and polyphenol-rich prebiotics, a synbiotic, attenuates the chronic-stress induced inflammatory responses in the ileum and the prefrontal cortex promoting resilience to the consequent depressive- and anxiety-like behaviors in male mice. ConclusionsOverall, this study characterizes a novel synbiotic treatment for chronic-stress induced behavioral impairments while defining a putative mechanism of gut-microbiota host interaction for modulating the peripheral and brain immune systems. Funding SourcesGrant AT008661 from the NIH’s ODS and the NCCIH.

Mechanisms underlying gut microbiota-host interactions in insects.

Insects are the most diverse group of animals and colonize almost all environments on our planet. This diversity is reflected in the structure and function of the microbial communities inhabiting the insect digestive system. As in mammals, the gut microbiota of insects can have important symbiotic functions, complementing host nutrition, facilitating dietary breakdown or providing protection against pathogens. There is an increasing number of insect models that are experimentally tractable, facilitating mechanistic studies of gut microbiota-host interactions. In this Review, we will summarize recent findings that have advanced our understanding of the molecular mechanisms underlying the symbiosis between insects and their gut microbiota. We will open the article with a general introduction to the insect gut microbiota and then turn towards the discussion of particular mechanisms and molecular processes governing the colonization of the insect gut environment as well as the diverse beneficial roles mediated by the gut microbiota. The Review highlights that, although the gut microbiota of insects is an active field of research with implications for fundamental and applied science, we are still in an early stage of understanding molecular mechanisms. However, the expanding capability to culture microbiomes and to manipulate microbe-host interactions in insects promises new molecular insights from diverse symbioses.

Alterations in Bile Acid Metabolism Associated With Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory disorder closely related to gut dysbiosis, which is associated with alterations in an important bacterial metabolite, bile acids (BAs). Although certain findings pertinent to BA changes in IBD vary among studies owing to the differences in sample type, quantitated BA species, study methodology, and patient characteristics, a specific trend concerning variations of BAs in IBD has been identified. In elaborating on this observation, it was noted that primary BAs and conjugated BAs are augmented in fecal samples but there is a reduction in secondary BAs in fecal samples. It is not entirely clear why patients with IBD manifest these changes and what role these changes play in the onset and development of IBD. Previous studies have shown that IBD-associated BA changes may be caused by alterations in BA absorption, synthesis, and bacterial modification. The complex relationship between bacteria and BAs may provide additional and deeper insight into host-gut microbiota interactions in the pathogenesis of IBD. The characteristic BA changes may generate profound effects in patients with IBD by shaping the gut microbiota community, affecting inflammatory processes, causing BA malabsorption associated with diarrhea, and even leading to intestinal dysplasia and cancer. Thus, therapeutic strategies correcting the alterations in the composition of BAs, including the elimination of excess BAs and the supplementation of deficient BAs, may prove promising in IBD.

A Systematic Pipeline to Enhance the Fecal Metabolome Coverage by LC-HRMS

The comprehended knowledge of the metabolic profile of the fecal matter has been recognized as an important point for understanding metabolic changes in the human systemic metabolism and it can provide precious information about host-gut microbiota interactions. However, few analytical strategies have been addressed for a broad analysis of metabolites with different chemical properties to better understand the chemical space of fecal samples. Here we report a systematic pipeline to achieve comprehensive coverage of the fecal metabolome, from high polar to nonpolar metabolites, using dog fecal samples as a proof-of-concept. This pipeline comprises a monophasic (ACN/H2O) and a biphasic extraction (methyl tert-butyl ether (MTBE)/MeOH/H2O) of the sample, followed by three liquid chromatography-high resolution tandem mass spectrometry (LC-HRMS/MS) methods using HILIC-amide, RP-C18 and CSH-C18 columns, and a switch polarity acquisition mode in the electrospray ion source. This approach allowed the annotation of 376 metabolites from 70 different chemical classes. The chemical space analysis by molecular networking and the pathway analysis revealed the complexity of the fecal sample and the importance of combined methods to better understand biochemical pathways. This pipeline can be used as a valuable tool to comprehend the relationship between host-gut microbiota metabolites and the influence of diet, medication, or environmental changes.

Vitamin D Modulates Intestinal Microbiota in Inflammatory Bowel Diseases.

Inflammatory bowel disease (IBD) is a chronic inflammation of the gastrointestinal tract (GIT), including Crohn’s disease (CD) and ulcerative colitis (UC), which differ in the location and lesion extensions. Both diseases are associated with microbiota dysbiosis, with a reduced population of butyrate-producing species, abnormal inflammatory response, and micronutrient deficiency (e.g., vitamin D hypovitaminosis). Vitamin D (VitD) is involved in immune cell differentiation, gut microbiota modulation, gene transcription, and barrier integrity. Vitamin D receptor (VDR) regulates the biological actions of the active VitD (1α,25-dihydroxyvitamin D3), and is involved in the genetic, environmental, immune, and microbial aspects of IBD. VitD deficiency is correlated with disease activity and its administration targeting a concentration of 30 ng/mL may have the potential to reduce disease activity. Moreover, VDR regulates functions of T cells and Paneth cells and modulates release of antimicrobial peptides in gut microbiota-host interactions. Meanwhile, beneficial microbial metabolites, e.g., butyrate, upregulate the VDR signaling. In this review, we summarize the clinical progress and mechanism studies on VitD/VDR related to gut microbiota modulation in IBD. We also discuss epigenetics in IBD and the probiotic regulation of VDR. Furthermore, we discuss the existing challenges and future directions. There is a lack of well-designed clinical trials exploring the appropriate dose and the influence of gender, age, ethnicity, genetics, microbiome, and metabolic disorders in IBD subtypes. To move forward, we need well-designed therapeutic studies to examine whether enhanced vitamin D will restore functions of VDR and microbiome in inhibiting chronic inflammation.

Characterization of the Kenyan Honey Bee (Apis mellifera) Gut Microbiota: A First Look at Tropical and Sub-Saharan African Bee Associated Microbiomes.

Gut microbiota plays important roles in many physiological processes of the host including digestion, protection, detoxification, and development of immune responses. The honey bee (Apis mellifera) has emerged as model for gut-microbiota host interaction studies due to its gut microbiota being highly conserved and having a simple composition. A key gap in this model is understanding how the microbiome differs regionally, including sampling from the tropics and in particular from Africa. The African region is important from the perspective of the native diversity of the bees, and differences in landscape and bee management. Here, we characterized the honey bee gut microbiota in sub-Saharan Africa using 16S rRNA amplicon sequencing. We confirm the presence of the core gut microbiota members and highlight different compositions of these communities across regions. We found that bees from the coastal regions harbor a higher relative abundance and diversity on core members. Additionally, we showed that Gilliamella, Snodgrassella, and Frischella dominate in all locations, and that altitude and humidity affect Gilliamella abundance. In contrast, we found that Lactobacillus was less common compared temperate regions of the world. This study is a first comprehensive characterization of the gut microbiota of honey bees from sub-Saharan Africa and underscores the need to study microbiome diversity in other indigenous bee species and regions.

Microbiota metabolites modulate the T helper 17 to regulatory T cell (Th17/Treg) imbalance promoting resilience to stress-induced anxiety- and depressive-like behaviors

Chronic stress disrupts immune homeostasis while gut microbiota-derived metabolites attenuate inflammation, thus promoting resilience to stress-induced immune and behavioral abnormalities. There are both peripheral and brain region-specific maladaptations of the immune response to chronic stress that produce interrelated mechanistic considerations required for the design of novel therapeutic strategies for prevention of stress-induced psychological impairment. This study shows that a combination of probiotics and polyphenol-rich prebiotics, a synbiotic, attenuates the chronic-stress induced inflammatory responses in the ileum and the prefrontal cortex promoting resilience to the consequent depressive- and anxiety-like behaviors in male mice. Pharmacokinetic studies revealed that this effect may be attributed to specific synbiotic-produced metabolites including 4-hydroxyphenylpropionic, 4-hydroxyphenylacetic acid and caffeic acid. Using a model of chronic unpredictable stress, behavioral abnormalities were associated to strong immune cell activation and recruitment in the ileum while inflammasome pathways were implicated in the prefrontal cortex and hippocampus. Chronic stress also upregulated the ratio of activated proinflammatory T helper 17 (Th17) to regulatory T cells (Treg) in the liver and ileum and it was predicted with ingenuity pathway analysis that the aryl hydrocarbon receptor (AHR) could be driving the synbiotic’s effect on the ileum’s inflammatory response to stress. Synbiotic treatment indiscriminately attenuated the stress-induced immune and behavioral aberrations in both the ileum and the brain while in a gut-immune co-culture model, the synbiotic-specific metabolites promoted anti-inflammatory activity through the AHR. Overall, this study characterizes a novel synbiotic treatment for chronic-stress induced behavioral impairments while defining a putative mechanism of gut-microbiota host interaction for modulating the peripheral and brain immune systems.

Changes in dietary fiber intake in mice reveal associations between colonic mucin O-glycosylation and specific gut bacteria

ABSTRACT The colonic mucus layer, comprised of highly O-glycosylated mucins, is vital to mediating host-gut microbiota interactions, yet the impact of dietary changes on colonic mucin O-glycosylation and its associations with the gut microbiota remains unexplored. Here, we used an array of omics techniques including glycomics to examine the effect of dietary fiber consumption on the gut microbiota, colonic mucin O-glycosylation and host physiology of high-fat diet-fed C57BL/6J mice. The high-fat diet group had significantly impaired glucose tolerance and altered liver proteome, gut microbiota composition, and short-chain fatty acid production compared to normal chow diet group. While dietary fiber inclusion did not reverse all high fat-induced modifications, it resulted in specific changes, including an increase in the relative abundance of bacterial families with known fiber digesters and a higher propionate concentration. Conversely, colonic mucin O-glycosylation remained similar between the normal chow and high-fat diet groups, while dietary fiber intervention resulted in major alterations in O-glycosylation. Correlation network analysis revealed previously undescribed associations between specific bacteria and mucin glycan structures. For example, the relative abundance of the bacterium Parabacteroides distasonis positively correlated with glycan structures containing one terminal fucose and correlated negatively with glycans containing two terminal fucose residues or with both an N-acetylneuraminic acid and a sulfate residue. This is the first comprehensive report of the impact of dietary fiber on the colonic mucin O-glycosylation and associations of these mucosal glycans with specific gut bacteria.

Gut Microbiota and Intestinal Trans-Epithelial Permeability.

Constant remodeling of tight junctions to regulate trans-epithelial permeability is essential in maintaining intestinal barrier functions and thus preventing diffusion of small molecules and bacteria to host systemic circulation. Gut microbiota dysbiosis and dysfunctional gut barrier have been correlated to a large number of diseases such as obesity, type 2 diabetes and inflammatory bowel disease. This led to the hypothesis that gut bacteria-epithelial cell interactions are key regulators of epithelial permeability through the modulation of tight junctions. Nevertheless, the molecular basis of host-pathogen interactions remains unclear mostly due to the inability of most in vitro models to recreate the differentiated tissue structure and components observed in the normal intestinal epithelium. Recent advances have led to the development of a novel cellular model derived from intestinal epithelial stem cells, the so-called organoids, encompassing all epithelial cell types and reproducing physiological properties of the intestinal tissue. We summarize herein knowledge on molecular aspects of intestinal barrier functions and the involvement of gut bacteria-epithelial cell interactions. This review also focuses on epithelial organoids as a promising model for epithelial barrier functions to study molecular aspects of gut microbiota-host interaction.

Comprehensive relationships between gut microbiome and faecal metabolome in individuals with type 2 diabetes and its complications.

As the treatment regimens such as metformin could confound the correlation between type 2 diabetes (T2D) and gut microbiome, we should revisit the relationship between gut microbiota and T2D patients who are not currently treated with metformin. The study recruited 65 T2D patients: 49 with and 16 without diabetic complications, and 35 healthy controls. We sequenced the 16S rRNA V3-V4 region of gut microbiota and detected metabolites based on liquid chromatography mass spectrometry (LC/MS) and gas chromatography mass spectrometry (GC/MS) in faecal samples. The composition of both the gut microbiota and faecal metabolites changed significantly with T2D patients. The abundance of Proteobacteria and the ratio of Firmicutes/Bacteroidetes were higher in T2D patients than healthy subjects, and the short chain fatty acids (SCFAs), bile acids and lipids of T2D patients were significantly disordered. Moreover, the abundances of certain SCFA-producing bacteria (Lachnospiraceae and Ruminococcaceae etc.) were significantly increased in T2D patients, while the faecal SCFAs concentrations were significantly decreased. It's suggested that the role of SCFA-producing bacteria was not simply to produce SCFAs. Then we identified 44 microbial modules to explore the correlations between the gut microbiota and metabolic traits. Specially, most modules including certain SCFA-producing bacteria were comprehensively correlated to body mass index, the levels of blood glucose, blood pressure, blood cholesterol and faecal bile acids and lipids. Our study identified the relationships between the gut microbiota and faecal metabolites, and provided a resource for future studies to understand host-gut microbiota interactions in T2D.

Emerging Applications of Metabolomics in Traditional Chinese Medicine Treating Hypertension: Biomarkers, Pathways and More.

Hypertension is a prevalent, complex, and polygenic cardiovascular disease, which is associated with increased mortality and morbidity. Across the world, traditional Chinese medicine (TCM) constituted by herbal medicine and non-pharmacological therapies is used to assist blood pressure management. Though widely accepted in daily practice, its mechanism remains largely unknown. Recent years saw a number of studies utilizing metabolomics technologies to elucidate the biological foundation of the antihypertensive effect of TCM. Metabolomics is a relatively “young” omics approach that has gained enormous attention recently in cardiovascular drug discovery and pharmacology studies of natural products. In this review, we described the use of metabolomics in deciphering TCM diagnostic codes for hypertension and in revealing molecular events that drive the antihypertensive effect. By corroborating the diagnostic rules, there's accumulating evidence showing that metabolic profile could be the signature of different syndromes/patterns of hypertension, which offers new perspectives for disease diagnosis and efficacy optimization. Moreover, TCM treatment significantly altered the metabolic perturbations associated with hypertension, which could be a crucial mechanism of the therapeutic effect of TCM. Not only significantly rebalances the dynamics of metabolic flux, TCM but also elicits metabolic network reorganization through restoring the functions of key metabolites, and metabolic pathways. The role of TCM in regulating metabolic perturbations will be informative to researchers seeking new leads for drug discovery. This review further envisioned the promises of employing metabolomics to explore network pharmacology, host-gut microbiota interactions and metabolic reprogramming in TCM, and possible herb-drug interactions in this field in future.

Brain-Gut-Microbiota Axis in Alzheimer's Disease.

Disturbances along the brain-gut-microbiota axis may significantly contribute to the pathogenesis of neurodegenerative disorders. Alzheimer’s disease (AD) is the most frequent cause of dementia characterized by a progressive decline in cognitive function associated with the formation of amyloid beta (Aβ) plaques and neurofibrillary tangles. Alterations in the gut microbiota composition induce increased permeability of the gut barrier and immune activation leading to systemic inflammation, which in turn may impair the blood-brain barrier and promote neuroinflammation, neural injury, and ultimately neurodegeneration. Recently, Aβ has also been recognized as an antimicrobial peptide participating in the innate immune response. However, in the dysregulated state, Aβ may reveal harmful properties. Importantly, bacterial amyloids through molecular mimicry may elicit cross-seeding of misfolding and induce microglial priming. The Aβ seeding and propagation may occur at different levels of the brain-gut-microbiota axis. The potential mechanisms of amyloid spreading include neuron-to-neuron or distal neuron spreading, direct blood-brain barrier crossing or via other cells as astrocytes, fibroblasts, microglia, and immune system cells. A growing body of experimental and clinical data confirms a key role of gut dysbiosis and gut microbiota-host interactions in neurodegeneration. The convergence of gut-derived inflammatory response together with aging and poor diet in the elderly contribute to the pathogenesis of AD. Modification of the gut microbiota composition by food-based therapy or by probiotic supplementation may create new preventive and therapeutic options in AD.