Host Gut Microbiota Research Articles

A Simplified Method for the Isolation of Extracellular Vesicles from Probiotic Bacteria and Their Characterization

Probiotic bacteria are normal inhabitants of a healthy human gut, conferring multiple beneficial effects on the gut and beyond. Under various disease states, the abundance and diversity of beneficial bacteria are significantly decreased, a process called dysbiosis. Among the intra- and extracellular components of probiotics, the extracellular vesicles (EVs) secreted by them have recently garnered significant attention as potential mediators of probiotics’ effects on host health. Further, these nanosized particles that encapsulate a wide range of bioactive molecules (proteins, lipids, RNA, and DNA) are standing out as key factors that could mediate gut microbiota–host communication and confer ameliorating effects in experimental inflammatory, metabolic, and cardiovascular disease models. However, a standard protocol of EV isolation from probiotic bacteria, not varying from lab to lab, must be established to achieve consistency in the experimental results in these pre-clinical models. Our current study compared two commonly used methods for EV isolation from biological samples, ultracentrifugation and precipitation, to develop a standard protocol for isolating EVs from the probiotics Lactobacillus acidophilus (LA), a Gram-positive bacterium, and Escherichia coli Nissle (EcN), a Gram-negative bacterium. The ultracentrifugation method gave ~1.5-fold higher EV yield for both LA and EcN compared to the precipitation method. Further, EcN released a higher level of EVs compared to LA. EVs were quantified and characterized by nanoparticle-tracking analysis (NTA) and by measuring the specific surface biomarkers using Western blot. Here, we describe our standardized step-by-step protocol for isolating EVs from probiotic bacteria and their characterization.

Pinworm microbiomes are distinct from their chipmunk host gut microbiota

Pinworm microbiomes are distinct from their chipmunk host gut microbiota

Specialized pro-resolving lipid mediators in gut immunophysiology: from dietary precursors to inflammation resolution.

This review aims to examine recent research on the role of specialized pro-resolving mediators (SPMs) in the regulation of gut immunophysiology. Inflammatory bowel disease (IBD) is characterized by chronic inflammation in the gastrointestinal tract, driven by disruptions in the intestinal barrier and an imbalance between the host immune system and gut microbiota. Dietary polyunsaturated fatty acids (PUFAs), especially ω-3 and ω-6, are key regulators of immune responses and help maintain the integrity of the intestinal barrier. These PUFAs serve as precursors to SPMs, lipid mediators that play a critical role in resolving inflammation. SPMs actively reprogram immune cells, promoting the clearance of cellular debris, reducing cytokine production, and restoring tissue homeostasis without suppressing the immune response. Emerging evidence indicates that in the gut, SPMs strengthen intestinal barrier function, modulate immune responses in colitis and colon cancer, and influence gut microbiota composition. The recent evidence strongly supports the central role of SPMs in maintaining gut health and restoring organ function following inflammatory challenges. This evidence highlights the potential of therapeutic approaches that target these pathways for both the prevention and treatment of gut-related inflammatory conditions.

Bacillus subtilis HGCC-1 improves growth performance and liver health via regulating gut microbiota in golden pompano

Probiotics as green inputs have been reported to regulate metabolism and immunity of fish. However, the mechanisms by which probiotics improve growth and health of fish are unclear. Therefore, the aim of this study was to investigate the effect of Bacillus subtilis HGCC-1, an indigenous probiotic isolated from fish, on growth performance, host lipid metabolism, liver inflammation and gut microbiota of golden pompano. 160,000 golden pompanos with the initial body weight of 93.6 ± 5.0 g was randomly assigned to two dietary groups: Control and HGCC-1 (control diet supplemented with 0.3 g/kg Bacillus subtilis HGCC-1 fermentation product), and after three weeks of feeding, 26 golden pompanos were randomly collected from each group for gut microbiome and host phenotype analysis. Dietary supplementation with Bacillus subtilis HGCC-1 significantly promoted growth performance (P < 0.05) and enhanced feed utilization. Besides, HGCC-1 improved liver health and alleviated hepatic steatosis and inflammation. Furthermore, Bacillus subtilis HGCC-1 enhanced intestinal lipid absorption, promoted hepatic utilization of dietary fat by improving hepatic lipid uptake/transport and fatty acid β-oxidation to provide energy, and reduced hepatic TG level (P < 0.05), which may be the potential mechanism of Bacillus subtilis HGCC-1-mediated growth promotion. Finally, Bacillus subtilis HGCC-1 significantly altered the structure and function of gut microbiota (P < 0.05), leading to enrichment of beneficial taxa such as Bacillus (P < 0.0001) and increased of the ratio of “Functional Group 2/Functional Group 1” (P = 0.00092). Interestingly, the ratio of “Functional Group 2/Functional Group 1” was linked to the growth traits (Spearman, P < 0.05), while the intestinal abundance of Bacillus was correlated with serum TG in fish (Spearman, R = 0.47, P = 0.00091), suggesting a role of the intestinal microbiota in HGCC-1 mediated effect on growth and lipid metabolism. In summary, Bacillus subtilis HGCC-1 promotes growth performance, alleviate hepatic steatosis and enhances liver health via regulating gut microbiota in golden pompano, which ultimately showed as beneficial effect of fish growth and health.

Citrus aurantium 'Changshan-huyou' physiological premature fruit drop: A promising prebiotic to tackle obesity.

Presently, the mitigation and governance of obesity have surfaced as significant public health dilemmas on a global scale. A wealth of studies indicated that the host gut microbiota is instrumental in regulating the interplay between high-fat diet (HFD) intake and the pathogenesis of obesity. Physiological premature fruit drop, a major byproduct of citrus, is rich in a variety of bioactive constituents, yet its potential has remained underutilized for an extended period. The objective of this investigation is to examine the chemical constituents of Citrus aurantium'Changshan-huyou' premature fruit drop (HYFD) and investigate its anti-obesity effects, elucidating its potential pathways. Volatile compounds and flavonoids in HYFD were analyzed using chromatographic and mass spectrometric techniques. Furthermore, this study utilized biochemical assays and histopathological examinations to evaluate the effects of HYFD on HFD-fed mice. The impact of HYFD on the gut microbiota of the mice was examined through 16S rRNA gene sequencing, and fecal microbiota transplantation was employed to validate the role of the gut microbial community in host obesity prevention. Concurrently, transcriptome was employed to identify differentially expressed genes, providing further insights into the molecular mechanisms through which HYFD manifests its anti-obesity effects. Our findings demonstrated that HYFD supplementation significantly alleviated adiposity and ameliorated the dysbiosis of gut microbiota in HFD-induced mice. HYFD rectified the HFD-induced gut microbiota dysregulation, enhanced the presence of beneficial microbial taxa linked to lipid metabolism, including Parabacteroides and Alistipes, and elevated concentrations of the anti-obesity short-chain fatty acids, comprising caproic acid and isocaproic acid. Additionally, transcriptomic analyses confirmed that HYFD prevented obesity in mice by enhancing fatty acid catabolism via the activation of the AMPK/PPARα/CPT1a signaling pathway. Our results provided novel insights into the mechanism of citrus physiological premature fruit drop and its potential role in preventing obesity, while sparking greater interest in leveraging more biomass waste.

In vivo mechanism of the interaction between trimethylamine lyase expression and glycolytic pathways.

Recent studies confirmed that host-gut microbiota interactions modulate disease-linked metabolite TMA production via TMA lyase. However, microbial enzyme production mechanisms remain unclear. In the present study, we investigated the impact of dietary and intervention factors on gut microbiota, microbial gene expression, and the interplay between TMA lyase and glycolytic pathways in mice. Using 16S rRNA gene sequencing, metagenomics, and metabolomics, the gut microbiota composition and microbial functional gene expression profiles related to TMA lyase and glycolytic enzymes were determined. The results revealed that distinct diets and intervention factors altered gut microbiota, gene expression, and metabolites linked to glycine metabolism and glycolysis. Notably, an arabinoxylan-rich diet suppressed genes linked to choline, glycine, glycolysis, and TMA lyase, favoring glycine utilization via pyruvate pathways. Glycolytic inhibitors amplified these effects, mainly inhibiting pyruvate kinase. Our findings underscored the crosstalk between TMA lyase and glycolytic pathways, regulating glycine levels, and suggested avenues for targeted interventions and personalized diets to curb choline TMA lyase production.

Time-restricted feeding ameliorates non-alcoholic fatty liver disease through modulating hepatic nicotinamide metabolism via gut microbiota remodeling

ABSTRACT Non-alcoholic fatty liver disease (NAFLD) has emerged as a global health concern, lacking specific therapeutic strategies. Time-restricted feeding (TRF) regimen demonstrated beneficial effects in NAFLD; however, the underlying mechanisms remain unclear. In this study, we established a NAFLD mouse model through a high-fat diet (HFD) and implemented the 16:8 TRF regimen for a duration of 6 weeks. We demonstrated that TRF remarkably alleviated hepatic steatosis in HFD mice. Of note, aldehyde oxidase 1 (AOX1), a key enzyme in hepatic nicotinamide (NAM) catabolism, exhibited apparent upregulation in response to HFD, leading to abnormal accumulation of N-Methyl-6-pyridone-3-carboxamide (N-Me-6-PY, also known as 2PY) and N-Methyl-4-pyridone-5-carboxamide (N-Me-4-PY, also known as 4PY), whereas it was almost restored by TRF. Both N-Me-6-PY and N-Me-4-PY promoted de novo lipogenesis and fatty acid uptake capacities in hepatocyte, and aggravated hepatic steatosis in mice either fed chow diet or HFD. In contrast, pharmacological inhibition of AOX1 was sufficient to ameliorate the hepatic steatosis and lipid metabolic dysregulation induced by HFD. Moreover, transplantation of fecal microbiota efficiently mimicked the modulatory effect of TRF on NAM metabolism, thus mitigating hepatic steatosis and lipid metabolic disturbance, suggesting a gut microbiota-dependent manner. In conclusion, our study reveals the intricate relationship between host NAM metabolic modification and gut microbiota remodeling during the amelioration of NAFLD by TRF, providing promising insights into the prevention and treatment of NAFLD.

Distinct microbes, metabolites, and the host genome define the multi-omics profiles in right-sided and left-sided colon cancer

BackgroundStudies have reported clinical heterogeneity between right-sided colon cancer (RCC) and left-sided colon cancer (LCC). However, none of these studies used multi-omics analysis combining genetic regulation, microbiota, and metabolites to explain the site-specific difference.MethodsHere, 494 participants from a 16S rRNA gene sequencing cohort (50 RCC, 114 LCC, and 100 healthy controls) and a multi-omics cohort (63 RCC, 79 LCC, and 88 healthy controls) were analyzed. 16S rRNA gene, metagenomic sequencing, and metabolomics analyses of fecal samples were evaluated to identify tumor location-related bacteria and metabolites. Whole-exome sequencing (WES) and transcriptome sequencing (RNA-seq) were conducted to obtain the mutation burden and genomic expression pattern.ResultsWe found unique profiles of the intestinal microbiome, metabolome, and host genome between RCC and LCC. The bacteria Flavonifractor plautii (Fp) and Fusobacterium nucleatum, the metabolites L-phenylalanine, and the host genes PHLDA1 and WBP1 were the key omics features of RCC; whereas the bacteria Bacteroides sp. A1C1 (B.A1C1) and Parvimonas micra, the metabolites L-citrulline and D-ornithine, and the host genes TCF25 and HLA-DRB5 were considered the dominant omics features in LCC. Multi-omics correlation analysis indicated that RCC-enriched Fp was related to the accumulation of the metabolite L-phenylalanine and the suppressed WBP1 signal in RCC patients. In addition, LCC-enriched B.A1C1 was associated with the accumulation of the metabolites D-ornithine and L-citrulline as well as activation of the genes TCF25, HLA-DRB5, and AC079354.1.ConclusionOur findings identify previously unknown links between intestinal microbiota alterations, metabolites, and host genomics in RCC vs. LCC, suggesting that it may be possible to treat colorectal cancer (CRC) by targeting the gut microbiota–host interaction.EBEnjMWs8zdx83po8jPsMqVideo

Host-microbiota interactions in the infant gut revealed by daily faecal sample time series

Aim: This study aims to explore the interplay between host immune factors and gut microbiota in human infants in vivo using time-series daily stool samples and identify biomarkers of host-microbe interactions. Methods: 216 faecal samples collected from infants aged 5-6 or 11-12 months were analysed for gut microbiota composition, total bacterial load, and biomarkers of immune function. Results: We identified indications of microbial stimulation of eosinophil cationic protein (ECP), IgA, calprotectin (Cal), intestinal alkaline phosphatase (IAP), and Bactericidal/permeability-increasing protein (BPI) at 6 and 12 months, as well as stimulation of lipocalin 2 (LCN2), lactoferrin (LTF), and alpha-defensin-5 only at 6 months. The associations between biomarker concentrations and bacterial population growth were primarily positive at 6 months and mostly negative at 12 months, suggesting increasing host regulation of the microbiota with age. The exceptions were IAP, which was predictive of declining bacterial populations at both time points, and Cal, whose associations changed from negative at 6 months to positive at 12 months. Conclusion: There is an age-associated development in the correlation pattern between bacterial population growth and the biomarker concentrations, suggesting that host-microbe interactions change during early development. Albumin appeared as a potential marker of gut permeability, while LCN2 seemed to correlate with gut transit time. Mucin degradation appeared to decrease with age. Mucin2 and IAP emerged as potentially important regulators of the bacterial populations in the infant gut. The study demonstrates the utility of biomarker and bacteria profiling from daily stool samples for analysing in vivo associations between the immune system and the gut microbiota and provides evidence of host regulation of the microbiota in infants.

Effects of feces storage conditions for host-microbiota screenings in C. elegans

Background and aimsCurrent research on host-gut microbiota interactions is hindered by almost infinite bacterial combinations depending on intrinsic characteristics, environment, and health status, which prevents large-scale screenings in mammals. For these reasons, the bacterivore model organism C. elegans has been developed to test the effects of gut microbiota extracts from mammals. This study tested whether storage conditions of mouse feces and fecal extracts modify normal C. elegans healthspan.MethodsFeces from mice were processed for microbiota extraction after collection or after one or twelve months at -80 °C and compared to microbiota extracted six months before and left at room temperature. Extracts were probed for bacterial composition, viability, and nutritional content and tested in synchronized wild-type (strain N2) worms for food preferences and intake, development, fat accumulation, brood size, and maximal lifespan.ResultsLong-term freezing of feces before microbiota extraction modified composition but did not negatively impact subsequent worm development, fat accumulation, reproduction, and maximal lifespan, whereas using samples extracted and left at room temperature after a long period of time resulted in robust avoidance and was detrimental for normal growth.ConclusionsUsing frozen feces to test for impacts of microbiota in C. elegans appears an appropriate method since it did not affect normal biology and healthspan, which supports protocols with already existing feces stored in biobanks for high-throughput phenotype screenings.

The Relationship Between Soil and Gut Microbiota Influences the Adaptive Strategies of Goitered Gazelles in the Qaidam Basin.

The gut microbiota is integral to the health and adaptability of wild herbivores. Interactions with soil microbiota can shape the composition and function of the gut microbiota, thereby influencing the hosts' adaptive strategies. As a result, soil microbiota plays a pivotal role in enabling wild herbivores to thrive in extreme environments. However, the influence of soil microbiota from distinct regions on host's gut microbiota has often been overlooked. We conducted the first comprehensive analysis of the composition and diversity of gut and soil microbiota in goitered gazelles across six regions in the Qaidam Basin, utilizing source tracking and ecological assembly process analyses. Significant differences were observed in the composition and diversity of soil and gut microbiota among the six groups. Source tracking analysis revealed that soil microbiota in the GangciGC (GC) group contributed the highest proportion to fecal microbiota (8.94%), while the Huaitoutala (HTTL) group contributed the lowest proportion (1.80%). The GC group also exhibited the lowest α-diversity in gut microbiota. The observed differences in gut microbial composition and diversity among goitered gazelles from six regions in the Qaidam Basin were closely tied to their adaptive strategies. Ecological assembly process analysis indicated that the gut microbiota were primarily influenced by stochastic processes, whereas deterministic processes dominated most soil microbial groups. Both the differences and commonalities in gut and soil microbiota play essential roles in enabling these gazelles to adapt to diverse environments. Notably, the utilization pattern of soil microbiota by gut microbiota did not align with regional trends in gut microbial α-diversity. This discrepancy may be attributed to variations in environmental pressures and the gut's filtering capacity, allowing gazelles to selectively acquire microbiota from soil to maintain homeostasis. This study highlights the significant regional variation in gut and soil microbiota diversity among goitered gazelle populations in the Qaidam Basin and underscores the critical role of soil-derived microbiota in their environmental adaptation.

Host-specific effects of Eubacterium species on Rg3-mediated modulation of osteosarcopenia in a genetically diverse mouse population

BackgroundOsteosarcopenia, characterized by the simultaneous loss of bone and muscle mass, is a serious health problem in the aging population. This study investigated the interplay between host genetics, gut microbiota, and musculoskeletal health in a mouse model of osteosarcopenia, exploring the therapeutic potential of gut microbiota modulation.MethodsWe examined the effects of Rg3, a phytochemical, on osteosarcopenia and its interactions with host genetics and gut microbiota in six founder strains of the Collaborative Cross (CC) population. Subsequently, we evaluated the therapeutic potential of Eubacterium nodatum (EN) and Eubacterium ventriosum (EV), two gut microbes identified as significant correlates of Rg3-mediated osteosarcopenia improvement, in selected C57BL/6 J (B6) and 129S1/SvImJ (129S1) mouse strains.ResultsRg3 treatment altered gut microbiota composition aligned with osteosarcopenia phenotypes, which response varied depending on host genetics. This finding enabled the identification of two microbes in the Eubacterium genus, potential mediator of Rg3 effect on osteosarcopenia. Oral administration of EN and EV differentially impacted bone density, muscle mass, exercise performance, and related gene expression in a mouse strain-specific manner. In 129S1 mice, EN and EV significantly improved these parameters, effectively reversing osteosarcopenic phenotypes. Mechanistic investigations revealed that these effects were mediated through the modulation of osteoblast differentiation and protein degradation pathways. In contrast, EN and EV did not significantly improve osteosarcopenic phenotypes in B6 mice, although they did modulate mitochondrial biogenesis and microbial diversity.ConclusionsOur findings underscore the complex interplay between host genetics and the gut microbiota in osteosarcopenia and emphasize the need for personalized treatment strategies. EN and EV exhibit strain-specific therapeutic effects, suggesting that tailoring microbial interventions to individual genetic backgrounds may be crucial for optimizing treatment outcomes.9Nfyi13u2tifXMNNi2cAAqVideo Graphical

The microbiome's influence on obesity: mechanisms and therapeutic potential.

In 2023, the World Obesity Atlas Federation concluded that more than 50% of the world's population would be overweight or obese within the next 12 years. At the heart of this epidemic lies the gut microbiota, a complex ecosystem that profoundly influences obesity-related metabolic health. Its multifaced role encompasses energy harvesting, inflammation, satiety signaling, gut barrier function, gut-brain communication, and adipose tissue homeostasis. Recognizing the complexities of the cross-talk between host physiology and gut microbiota is crucial for developing cutting-edge, microbiome-targeted therapies to address the global obesity crisis and its alarming health and economic repercussions. This narrative review analyzed the current state of knowledge, illuminating emerging research areas and their implications for leveraging gut microbial manipulations as therapeutic strategies to prevent and treat obesity and related disorders in humans. By elucidating the complex relationship between gut microflora and obesity, we aim to contribute to the growing body of knowledge underpinning this critical field, potentially paving the way for novel interventions to combat the worldwide obesity epidemic.

Invasive Fascioloides magna infections impact gut microbiota in a definitive host in Europe

Invasive parasites that expand their natural range can be a threat to wildlife biodiversity and may pose a health risk to non-adapted, naive host species. The invasive giant liver fluke, Fascioloides magna, native to North America, has extended its range in Europe and uses mainly red deer (Cervus elaphus) as definitive hosts. The penetration of the intestinal barrier by the young flukes to reach the liver via the abdominal cavity as well as the release of fluke metabolism products and excreta with the bile and/or changes in the microbial community of the biliary system may enable the translocation of intestinal bacteria across the intestinal barrier and, in turn, could be associated with inflammation and changes in the intestinal bacterial community. The gut commensal community plays a key role in host nutrition and interacts with cells of the immune system to maintain host health. For this study, the gut bacterial community of red deer infected with F. magna and of non-infected red deer from one of the largest forest ecosystems in Central Europe, located on the border between the Czech Republic and Germany, was investigated. The individual fluke burden was associated with changes in the gut microbial composition of the gut of infected individuals, whereas the diversity and composition of the gut bacteria were only slightly different between fluke-infected and uninfected deer. Several bacterial taxa at the genus level were unique to individuals carrying either one or many liver flukes. Our results suggest that the microbiota of red deer is stable to perturbation by low numbers of F. magna. However, a larger parasite burden may cause changes in the gut microbial composition in definitive hosts implying that non-invasive fecal microbiome assessments could serve as indicator for wildlife health monitoring.

Integrative analysis of gut microbiome and host transcriptome reveal novel molecular signatures in Hashimoto's thyroiditis

BackgroundHashimoto's thyroiditis (HT) is an autoimmune disorder with unclear molecular mechanisms. While current diagnosis is well-established, understanding of the gut-thyroid axis in HT remains limited. This study aimed to uncover novel molecular signatures in HT by integrating gut metagenome and host transcriptome data (miRNA/mRNA), potentially elucidating disease pathogenesis and identifying new therapeutic targets.MethodsWe recruited 31 early HT patients and 30 healthy controls in a two-stage study (discovery and validation). Blood and fecal samples underwent RNA and metagenomic sequencing, respectively. Integrative analysis included differential expression, weighted correlation network, correlation and random forest analyses. Regression models and ROC curve analysis were used to evaluate the significance of identified molecular signatures in HT.ResultsIntegrative analysis revealed subtle changes in gut microbiota diversity and composition in early HT, increased abundance of Bacillota_A and Spirochaetota at the phylum level, and significant differences in 24 genera and 67 species. Ecological network analysis indicated an imbalance in the gut microbiota with reduced inhibitory interactions against pathogenic genera in HT. Functional analysis showed changes in infection- and immune-related pathways. Three characteristic species (Salaquimonas_sp002400845, Clostridium_AI_sp002297865, and Enterocloster_citroniae) were identified as most relevant to HT. Analysis of miRNA and mRNA expression profiles uncovered pathways related to immune response, inflammation, infection, metabolism, proliferation, and thyroid cancer in HT. Based on correlations with HT and interactions between them, six characteristic RNAs (hsa-miR-548aq-3p, hsa-miR-374a-5p, GADD45A, IRS2, SMAD6, WWTR1) were identified. Furthermore, our study uncovered significant gut microbiota-host transcriptome interactions in HT, revealing enrichment in metabolic, immune, and cancer-related pathways, particularly with strong associations among those 9 key molecular signatures. The validation stage confirmed improved HT classification accuracy by combining these signatures (AUC = 0.95, ACC = 0.85), suggesting their potential significance in understanding HT pathogenesis.ConclusionOur study reveals novel molecular signatures linking gut microbiome and host transcriptome in HT, providing new insights into the disease pathogenesis. These findings not only enhance our understanding of the gut-thyroid axis but also suggest potential new directions for therapeutic interventions in HT.

Weizmannia coagulans BC99 affects valeric acid production via regulating gut microbiota to ameliorate inflammation and oxidative stress responses in Helicobacter pylori mice.

Helicobacter pylori is a highly prevalent pathogen in human gastric mucosa epithelial cells with strong colonization ability. Weizmannia coagulans is a kind of active microorganism that is beneficial to the improvement of host gut microbiota balance and can prevent and treat intestinal diseases. We investigated the beneficial effects of W. coagulans BC99 in H. pylori infected mice and measured inflammation response, oxidative stress, and gut microbiota. Results showed that BC99 could alleviate the gastric inflammation, inhibit the increasing of inflammation parameters endotoxin, interleukin-10, transforming growth factor-β, and interferon-γ and oxidative stress myeloperoxidase and malondialdehyde, promote the levels of superoxide dismutase and catalase. Furthermore, 16S rRNA gene sequencing analysis revealed that BC99 reversed the change of gut microbiota by reducing the abundance of Olsenella, Candidatus_Saccharimonas, Monoglobus, and increasing the abundance of Tyzzerella. Meanwhile, BC99 caused elevated levels of Ligilactobacillus and Lactobacillus. In view of the beneficial effect of BC99 on the content of short-chain fatty acid, valeric acid with sodium valerate interfered with H. pylori infection in mice found that valeric acid had a good restorative effect of H. pylori infection relating inflammation and oxidative stress responses. These results suggest that W. coagulans BC99 can be used as a potential probiotic to prevent and treat H. pylori infection by regulating the inflammation, oxidative stress, and gut microbiota.

Pristimerin Alleviates DSS-Induced Colitis in Mice by Modulating Intestinal Barrier Function, Gut Microbiota Balance and Host Metabolism.

Pristimerin is a pentacyclic triterpenoid mainly derived from Celastraceae plants such as Maytenus ilicifolia, which has been traditionally used for the treatment of gastrointestinal disorders. Pharmacological studies have shown that pristimerin exhibited anti-inflammatory, antioxidant, anticancer and antibacterial activities. However, the potential mechanism of pristimerin for the treatment of ulcerative colitis (UC) remains elusive. In the present study, pristimerin could effectively inhibit the NO generation induced by LPS in RAW 264.7 cells and upregulate the decreased expression of tight junction proteins such as occludin and claudin-1. In vivo, oral administration of pristimerin (0.5 mg/kg and 1 mg/kg) could significantly relieve UC symptoms such as body weight loss, disease activity index, shortened colon length and colonic pathological damage. Meanwhile, pristimerin decreased the TNF-α, MPO and MDA levels and increased the levels of IL-10, IL-22, SOD activity, occludin and claudin-1 in colon tissues. Gut microbiota analysis of cecum contents revealed that pristimerin treatment effectively alleviated gut microbiota dysbiosis. Additionally, serum metabolomics showed that 33 potential biomarkers involving lipid and tryptophan metabolism were identified, which may account for the therapeutic effects of pristimerin on UC mice. In conclusion, our findings indicate that pristimerin attenuates UC symptoms in DSS-induced mice through modulating intestinal barrier integrity, gut microbiota composition, lipid and tryptophan metabolism.

Pathobiont and symbiont contribute to microbiota homeostasis through Malpighian tubules-gut countercurrent flow in Bactrocera dorsalis.

Host-gut microbiota interactions are more complex than good or bad. Both gut symbiotic bacteria and pathobionts can provide essential functions to their host in one scenario and yet be detrimental to host health in another. So, these gut-dwelling bacteria must be tightly controlled to avoid harmful effects on the host. However, how pathobionts and other symbiotic bacteria coordinate to establish a host immune defense system remains unclear. Here, using a Tephritidae fruit fly Bactrocera dorsalis, we report that both pathobionts and other gut symbiotic bacteria release tyramine, which is recognized by the host insects. These tyramines induce the formation of insect-conserved Malpighian tubules-gut countercurrent flow upon bacterial infection, which requires tyramine receptors and aquaporins. At the same time, pathobionts but not gut symbiotic bacteria induce the generation of reactive oxygen species, which are preserved by the countercurrent flow, promoting bacteria elimination through increasing gut peristalsis. More importantly, our results show that the Malpighian tubules-gut countercurrent flow maintains proper microbiota composition. Our work suggests a model where pathobiont-induced reactive oxygen species are preserved by Malpighian tubules-gut countercurrent flow involving both pathobionts and symbiotic bacteria. Furthermore, our work provides a Malpighian tubules-gut interaction that ensures efficient maintenance of the gut microbiota.

Host genetics and gut microbiota influence lipid metabolism and inflammation: potential implications for ALS pathophysiology in SOD1G93A mice

Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disorder characterized by the progressive loss of motor neurons, with genetic and environmental factors contributing to its complex pathogenesis. Dysregulated immune responses and altered energetic metabolism are key features, with emerging evidence implicating the gut microbiota (GM) in disease progression. We investigated the interplay among genetic background, GM composition, metabolism, and immune response in two distinct ALS mouse models: 129Sv_G93A and C57Ola_G93A, representing rapid and slow disease progression, respectively.Using 16 S rRNA sequencing and fecal metabolite analysis, we characterized the GM composition and metabolite profiles in non-transgenic (Ntg) and SOD1G93A mutant mice of both strains. Our results revealed strain-specific differences in GM composition and functions, particularly in the abundance of taxa belonging to Erysipelotrichaceae and the levels of short and medium-chain fatty acids in fecal samples. The SOD1 mutation induces significant shifts in GM colonization in both strains, with C57Ola_G93A mice showing changes resembling those in 129 Sv mice, potentially affecting disease pathogenesis. ALS symptom progression does not significantly alter microbiota composition, suggesting stability.Additionally, we assessed systemic immunity and inflammatory responses revealing strain-specific differences in immune cell populations and cytokine levels.Our findings underscore the substantial influence of genetic background on GM composition, metabolism, and immune response in ALS mouse models. These strain-specific variations may contribute to differences in disease susceptibility and progression rates. Further elucidating the mechanisms underlying these interactions could offer novel insights into ALS pathogenesis and potential therapeutic targets.

Unraveling the Gut Microbiota: Implications for Precision Nutrition and Personalized Medicine.

Recent studies have shown a growing interest in the complex relationship between the human gut microbiota, metabolism, and overall health. This review aims to explore the gut microbiota-host association, focusing on its implications for precision nutrition and personalized medicine. The objective is to highlight how gut microbiota modulate metabolic and immune functions, contributing to disease susceptibility and wellbeing. The review synthesizes recent research findings, analyzing key studies on the influence of gut microbiota on lipid and carbohydrate metabolism, intestinal health, neurobehavioral regulation, and endocrine signaling. Data were drawn from both experimental and clinical trials examining microbiota-host interactions relevant to precision nutrition. Our findings highlight the essential role of gut microbiota-derived metabolites in regulating host metabolism, including lipid and glucose pathways. These metabolites have been found to influence immune responses and gut barrier integrity. Additionally, the microbiota impacts broader physiological processes, including neuroendocrine regulation, which could be crucial for dietary interventions. Therefore, understanding the molecular mechanisms of dietary-microbiota-host interactions is pivotal for advancing personalized nutrition strategies. Tailored dietary recommendations based on individual gut microbiota compositions hold promise for improving health outcomes, potentially revolutionizing future healthcare approaches across diverse populations.