Gut Immune Cells Research Articles

CD8 + T cells may mediate the effect of gut microbiota on psoriasis: evidence from two-step mendelian randomization and bayesian weighting.

Emerging research indicates that gut microbiota and the associated immune responses are crucial in the development of chronic inflammatory skin diseases. This investigation employs Mendelian Randomization (MR) and Bayesian weighting to elucidate the causal links between gut microbiota, immune cells, and psoriasis, with a specific emphasis on CD8 + T cells. We leveraged summary statistics from genome-wide association studies (GWAS) related to gut microbiota, immune cells, and psoriasis. Single nucleotide polymorphisms (SNPs) were chosen as instrumental variables (IVs) to evaluate causal relationships through various MR methods, such as inverse variance weighted (IVW), MR Egger, weighted median, and simple mode. Additionally, Bayesian weighting was used to validate results and account for potential pleiotropy. The IVW analysis revealed significant associations between certain gut microbiota and psoriasis, notably identifying a protective link between Escherichia coli and psoriasis. Further MR analysis demonstrated that Escherichia coli had a causal relationship with CD8 + T cells. Increased levels of CD8 + T cells were associated with a higher risk of psoriasis. BWMR analysis confirmed these findings, showing that CD8 + T cells mediated 10.09% of the protective effect of Escherichia coli on psoriasis. This study underscores the significant role of Escherichia coli and CD8 + T cells in psoriasis, suggesting both protective and exacerbating effects. Understanding these microbiota-immune interactions can lead to the development of more effective, personalized treatments and preventative strategies, ultimately improving patient outcomes and quality of life.

Role of Crosstalk Between Gut Microbiota and Immune Cells in Colorectal Cancer: A Narrative Review

Abstract Colorectal cancer (CRC) ranks among the most prevalent and deadly cancers globally, with its incidence increasing due to lifestyle factors such as increased consumption of red meat and decreased vegetable intake. A distinctive aspect of CRC is its strong connection to the gut microbiota, which is crucial in both tumorigenesis and immune regulation. This narrative review provides a comprehensive analysis of the interactions between gut microbiota and the immune system, focusing on their importance in CRC progression and responses to immunotherapy. Imbalances in the composition of gut microbes are strongly associated with CRC development. Notably, species such as Fusobacterium nucleatum and Bacteroides fragilis have been identified as key regulators of immune responses within the tumor microenvironment. These microbes affect the functions of immune cells, such as T cells, macrophages and myeloid-derived suppressor cells, thereby influencing cancer progression and prognosis. Additionally, this review underscores the potential of gut microbiota as biomarkers for CRC detection and outcome prediction. There is also growing interest in the use of probiotics, fecal microbiota transplantation and dietary modifications as supplementary treatments. A deeper understanding of how microbial communities interact with the immune system may pave the way for novel personalized therapies, particularly by enhancing the effectiveness of immune checkpoint inhibitors.

Gut microbiota, immune cells, and chronic sinusitis: A Mendelian randomization analysis.

Allergic rhinitis (AR) is a common allergic inflammatory disease that affects the upper respiratory tract. Although previous research suggests a potential association between gut microbiota alterations and AR, the causal relationship remains unclear. This study employs Mendelian randomization (MR) to reduce confounding factors and reverse causality. By using genetic variants as instrumental variables, the MR approach aims to provide more reliable causal evidence of the relationship between gut microbiota, immune-related antibodies, and AR. This study utilized large-scale genome-wide association study data from the FINRISK 2002 cohort and the UK Biobank to systematically investigate the causal relationships between gut microbiota, antibody immune responses, and AR through a 2-sample MR approach. We applied the inverse variance weighting method to assess the potential mediating role of antibody immune responses in the interaction between gut microbiota and AR. MR analysis identified 17 gut microbiomes significantly associated with chronic rhinosinusitis (CRS) risk. Specifically, increased abundances of the CAG-884 and UBA1407 species were linked to a higher CRS risk, while greater levels of Atopobiaceae and Bacteroides thetaiotaomicron were associated with a reduced risk. In addition, of the 29 immune cell types correlated with CRS, 12 were found to increase risk, while 17 reduced it. Notably, CAG-884 indirectly influenced CRS risk by affecting the proportion of TD double negative (CD4-CD8-) % T cells, with a mediating effect ratio of 36.4%. Our findings confirm a causal relationship between gut microbiota and immune cells in relation to CRS, underscoring the mediating role of immune cells in this interaction.

HFD aggravated the arthritis and atherosclerosis by altering the intestinal status and gut microbiota

AbstractRheumatoid arthritis (RA) and cardiovascular disease (CVD) are both the chronic inflammatory disease. To investigate the influence of secondary atherosclerosis on arthritis mice, we treated the ApoE−/− mice with K/BxN serum and high fat diet (HFD), and subsequently assessed the phenotypes as well as immune profiles of K/BxN serum and HFD induced ApoE−/− mice. We found that HFD treatment aggravated the hyperlipidemia, atherosclerotic lesions, ankle swelling and arthropathy of mice. We further demonstrated that HFD altered the gut microbiota and metabolism, intestinal homeostasis and Th17/Treg cell balance in lamina propria lymphocytes. Moreover, HFD decreased the number of Peyer’ s patches and altered the expression profiling of gut immune cells. In addition, HFD increased the number of aortic leukocytes and macrophages, then aggravated the atherosclerosis in aorta, which led to greater inflammation in mice aorta and aortic root. Collectively, our study indicated that HFD aggravated the arthritis and atherosclerosis, which may be contributed by microbiota dysbiosis, the intestinal permeability and disrupted immunological homeostasis.

An untargeted metabolomic study using MALDI-mass spectrometry imaging reveals region-specific biomarkers associated with bowel inflammation

IntroductionInflammatory bowel diseases (IBDs) are chronic immune driven intestinal disorders with marked metabolic alteration. Mass spectrometry imaging (MSI) enables the direct visualization of biomolecules within tissues and facilitates the study of metabolic changes. Integrating multiple spatial information sources is a promising approach for discovering new biomarkers and understanding biochemical alteration within the context of the disease.ObjectiveThis study evaluates the metabolomic changes in gut tissue samples from a preclinical model of spontaneous colitis, the HLA-B27/hβ2m transgenic rat, to uncover disease biomarkers.MethodsWe applied MSI to study the biochemical profile of bowel samples from HLA-B27/hβ2m transgenic and WT control rats in an unbiased manner. Statistical comparison was used to identify discriminative features. Some features were annotated using LC-MS/MS. The significance of these discriminative features was evaluated based on their distribution within histological layers and the presence of immune infiltration.ResultsWe identified spatially resolved changes in the metabolomic pattern of HLA-B27+ samples compared to WT controls. Out of the 275 discriminative features identified, 83 were annotated as metabolites. Two functional groups of discriminative metabolites were discussed as markers of gut barrier impairment and immune cell infiltration.ConclusionMS imaging’s spatial dimension provides insights into disease mechanisms through the identification of spatially resolved biomarkers.

Exploring the relationship between gut microbiota, immune characteristics, and female genital tract polyps using genetic evidence.

The study investigates the causal relationship between gut microbes and female genital tract polyps, exploring the potential mediating role of immune cells via Mendelian randomization (MR) analysis. Our MR study was designed following the STROBE-MR guidelines. We combined data from a large-scale GWAS meta-analysis, including 731 immune profiles and female genital tract polyps, with gut microbiology data sourced from the MiBioGen consortium. Univariate Mendelian randomization was employed to identify gut microbes and immune profiles significantly associated with female genital tract polyps causally. A 2-step MR analysis was utilized to investigate the potential mediating role of immune cells. Furthermore, we utilized the multivariable MR approach based on Bayesian model averaging (MR-BMA) to further assess the prioritization of gut microbiota vs immune characteristics in the development of female genital tract polyps. Through univariate MR analysis, we identified a significant causal link between 12 gut microbiota, 31 immune features, and female genital tract polyps. Four causal pathways involving gut microbiota, immune cells, and polyps were identified among them. MR-BMA analysis indicated marginal inclusion probability (MIP) values exceeding 0.1 for 5 gut microbiota groups: Victivallaceae (model-averaged causal estimate [MACE] = 0.060, MIP = 0.581, P = .0089), Ruminococcus gautreuii (MACE = 0.052, MIP = 0.346, P = .0640), Lachnoclostrium (MACE = 0.0380, MIP = 0.225, P = .1875), Alphaprobacter (MACE = 0.0186, MIP = 0.140, P = .3934), and Fusicatenibacter (MACE = 0.013, MIP = 0.110, P = .5818). Six immune features exhibit high priority, with MIP values exceeding 0.5, including HLA DR on CD33+ HLA DR+ CD14dim (MACE = -0.015, MIP = 0.753, P = .0853), HVEM on naive CD4+ T cell (MACE = 0.024, MIP = 0.737, P = .0053), CD80 on CD62L+ plastic cytoplasmic dendritic cell (MACE = 0.024, MIP = 0.721, P = .0228), CD28 on activated and secret CD4 regulatory T cell (MACE = 0.0054, MIP = 0.706, P = .3245), HLA DR on CD14+ CD16 monocyte (MACE = -0.0003, MIP = 0.520, P = .7927), HLA DR on CD14+ monocyte (MACE = -0.0029, MIP = 0.509, P = .5576). Our research indicates that gut microbiota exerts an independent causal influence on female genital tract polyps, potentially impacting them via various immune cells.

Causality between gut microbiota, immune cells, and breast cancer: Mendelian randomization analysis.

The association between gut microbiota (GM) and breast cancer (BC) has been studied. Nevertheless, the causal relationship between them and the potential mediating factors have not been clearly defined. Therefore, in this study, Mendelian randomization analysis (MR) was employed to explore the causal relationship between 473 GM and BC, as well as the mediating effect of potential immune cells. In this investigation, we availed ourselves of the publicly accessible summary statistics from the genome-wide association study to undertake two-sample and reverse Mendelian randomization analyses on GM and BC, with the intention of clarifying the causal association between GM and BC. Subsequently, through the application of the two-step Mendelian randomization analysis, it was revealed that the relationship between GM and BC was mediated by immune cells. The stability of the research outcomes was verified via sensitivity analysis. Mendelian randomization analysis elucidated the protective impacts of 8 genera on BC (such as Phylum Actinobacteriota, Species Bacteroides A plebeius A, Species Bifidobacterium adolescentis, Species CAG-841 sp002479075, Family Fibrobacteraceae, Order Fibrobacterales, Class Fibrobacteria, and Species Phascolarctobacterium sp003150755). Additionally, there are 23 immune cell traits related to BC. Our research findings showed that the species Megamonas funiformis was associated with an increased risk of BC, and 11.20% of this effect was mediated by CD38 on IgD+ CD24-. Likewise, HLA DR on CD33br HLA DR+ CD14- mediated the causal relationship between Species Prevotellamassilia and BC, having a mediating ratio of 7.89%. This study clarifies a potential causal relationship between GM, immune cells, and BC and provides genetic evidence for this causal connection. It offers research directions for the subsequent prevention and treatment of BC through the interaction between GM and immune cells, and provides a reference for future mechanistic and clinical studies in this field.

Causal Links Between gut microbiota, blood metabolites, immune cells, inflammatory proteins, and myopia: Mendelian Randomization study

Causal Links Between gut microbiota, blood metabolites, immune cells, inflammatory proteins, and myopia: Mendelian Randomization study

Causal Relationships Between Gut Microbiota, Immune Cell and Pancreatic Cancer: A Two-Step, Two-Sample Mendelian Randomization Study.

Gut microbiota (GM) is associated with both the occurrence and development of pancreatic cancer (PC), and immune cells potentially play a role in this process. This study sought to evaluate the causative effect of GM on PC and to ascertain possible immune cell mediators. The study primarily employed a two-step, two-sample Mendelian randomization (MR) analysis to explore the causal relationship between GM and PC within the European population, placing particular emphasis on the application of the inverse variance weighted (IVW) approach. Additionally, mediation analysis was conducted to explore the potential influence of immune cells as mediators. The MR analysis revealed a significant association between Geminocystis and the risk of PC. Increased abundance of Geminocystis was positively associated with the risk of PC (odds ratio (OR): 2.580, 95% confidence interval (CI): 1.050 - 6.342). The validity of the outcomes was also verified by the sensitivity analysis. The mediation MR analysis showed that the B-cell absolute count served as a partial intermediary in the causal link between Geminocystis and the risk of PC, contributing to 15.321% of the mediating impact. This MR study demonstrated that Geminocystis has a causal relationship with PC and potentially mediates B-cell absolute count in the TBNK panel.

Unraveling the role of gut microbiota and immune cells in thyroid cancer and tumor drug resistance

The gut microbiota (GM) and immune cells (IC) are increasingly recognized as key players in cancer development and progression. This study aimed to explore the potential mediating role of IC in the causal relationship between GM and thyroid cancer (TC) using Mendelian randomization (MR) analysis. Data from genome-wide association studies (GWAS) encompassing 473 GM species, 731 IC types, and TC were utilized. MR analysis identified nine GM species with significant causal relationships to TC, mediated by 10 IC phenotypes such as "Switched Memory AC," "IgD-CD38dim AC," and "EM DN (CD4-CD8-) AC." These findings suggest a complex interplay where specific IC mediate the effects of GM on TC risk. Sensitivity analyses confirmed the robustness of these results, with no evidence of horizontal pleiotropy. This study highlights potential mechanisms linking GM and IC to TC, offering insights that could inform GM-based immunotherapeutic strategies and IC-targeted interventions. However, further experimental research is needed to validate these causal pathways and better understand the underlying biological mechanisms.

A two-step, two-sample Mendelian randomization analysis investigating the interplay between gut microbiota, immune cells, and melanoma skin cancer.

This study aims to rigorously explore the potential causal relationships among gut microbiota (GM), immune cells, and melanoma skin cancer among participants from Europe, where this disease exhibits significant prevalence and profound societal impact. Using the genome-wide association analysis database, a double-sample Mendelian randomization (MR) analysis was drawn upon to investigate GM, immune cells, and melanoma skin cancer. The inverse variance weighted approach was applied to estimate the causal connections among these variables. A two-step MR analysis was employed to quantitatively gauge the impact of immune cells mediated GM on melanoma skin cancer. To address potential sources of bias, such as pleiotropy and heterogeneity, multiple analytical techniques were integrated. The MR analysis pinpointed 6 GM taxa related to either an augmented or declined risk of late-stage melanoma skin cancer. In the same vein, 32 immune cell phenotypes were noticed as correlates with modified risk of melanoma skin cancer. Our study also implies that the probable association between GM and melanoma could be facilitated by 5 immune cell phenotypes. The findings of our study underline certain GM taxa and immune cells as potential influencers on the onset and development of melanoma skin cancer. Importantly, our results spotlight 5 immune cell phenotypes as potential agents mediating this association.

Exploring the mediating role of immune cells in the pathogenesis of IgA nephropathy through the inflammatory axis of gut microbiota from a genomic perspective.

IgA nephropathy (IgAN) is a chronic glomerular disease characterized by the deposition of IgA antibodies in the kidney's mesangium. Its pathogenesis involves genetic, immune, and environmental factors, particularly within the mucosal immune system and gut microbiota. Immune cells play a central role in mediating these processes, which this study investigates using Mendelian Randomization (MR) to explore causal relationships among gut microbiota, inflammatory markers, blood cells, and immune cells in IgAN pathogenesis. We conducted a two-sample MR analysis using Genome-Wide Association Study (GWAS) summary data to assess the causal effects of gut microbiota, inflammatory markers, and blood cell traits on IgAN. Data sources included the FinnGen dataset for IgAN and relevant GWAS datasets for immune traits, blood cells, and inflammatory markers. Inverse variance weighting (IVW) was the primary MR method, supported by sensitivity analyses. We particularly examined the mediation effect of immune cells on these exposures' influence on IgAN. Significant associations were found between several factors and IgAN. Gut microbiota traits, such as Firmicutes E and Sporomusales, increased IgAN risk, while Citrobacter A and Herbinix reduced it. Inflammatory markers, including Interleukin-10 and Fibroblast Growth Factor 23, promoted IgAN onset. Blood cell traits like red blood cell perturbation response increased risk, while monocyte perturbation response was protective. Immune traits played a key mediating role, with Transitional %B cells reducing IgAN risk and CD28- CD25 + + CD8br %T cells increasing it. This study highlights the pivotal mediating role of immune cells in the interactions between gut microbiota, inflammatory markers, and IgAN risk. These findings identify potential biomarkers and therapeutic targets, providing new insights into the immune mechanisms underlying IgAN and opportunities for intervention.

Transport functions of intestinal lymphatic vessels.

Lymphatic vessels are crucial for fluid absorption and the transport of peripheral immune cells to lymph nodes. However, in the small intestine, the lymphatic fluid is rich in diet-derived lipids incorporated into chylomicrons and gut-specific immune cells. Thus, intestinal lymphatic vessels have evolved to handle these unique cargoes and are critical for systemic dietary lipid delivery and metabolism. This Review covers mechanisms of lipid absorption from epithelial cells to the lymphatics as well as unique features of the gut microenvironment that affect these functions. Moreover, we discuss details of the intestinal lymphatics in gut immune cell trafficking and insights into the role of inter-organ communication. Lastly, we highlight the particularities of fat absorption that can be harnessed for efficient lipid-soluble drug distribution for novel therapies, including the ability of chylomicron-associated drugs to bypass first-pass liver metabolism for systemic delivery. In all, this Review will help to promote an understanding of intestinal lymphatic-systemicinteractionsto guide future research directions.

Genetic link between gut microbiota, immune cells, and rheumatoid arthritis: Mechanism of action of CD28 proteins

The gut microbiota serves a crucial function in modulating the immune responses of the host, as well as in managing inflammation within the body. In this particular study, the researchers sought to delve deeper into the specific mechanisms through which CD28 interacts with the gut microbiota and influences the functionality of immune cells. The study collected intestinal microbial samples from RA patients and healthy controls, analyzed microbial composition by high-throughput sequencing, and detected CD28 expression in T cells in combination with cellular immunology methods. At the same time, the effects of CD28 deletion on intestinal microbiota changes and inflammatory responses were evaluated using animal models. The findings from this study revealed a notable distinction in the gut microbiota profiles of individuals diagnosed with rheumatoid arthritis (RA) when compared to those of healthy control subjects. Specifically, the abundance of certain microbial species was observed to have a negative correlation with the expression levels of CD28, highlighting a complex interaction between the gut microbiome and the immune regulatory mechanisms involved in RA. Furthermore, experiments conducted on mice lacking CD28 demonstrated considerable alterations in their gut microbiota composition. These Cd28-deficient mice exhibited elevated levels of inflammatory markers, indicating an interplay between CD28 and the regulation of both the microbiota and the immune response.

Molecular patterns of microbial and metabolic interactions in septic patients with persistent lymphopenia

BackgroundPersistent lymphopenia can be regarded as an important index of acquired immune dysfunction in sepsis. Whether the specific immune factor changes in septic patients with lymphopenia and the correlation to gut microbiota and metabolites remain unclear. MethodsThis single-center prospective observation conducted lymphocyte subgroup analysis of blood samples and 16S rRNA gene amplicons sequencing and untargeted metabolomics analysis of fecal samples from 36 subjects with the persistent (≥3d) (n = 21) and non-persistent lymphopenia (<3d) (n = 15). ResultsThe persistent lymphopenia showed higher the 28d mortality and 90d mortality, while significantly lower CD3+T/LY, CD3+T cells, CD3+CD4+T cells, CD3+CD8+T cells, Th1 cells, Th2 cells, CD45RA + Treg cells. The 16S rRNA results showed that Staphylococcus, Peptostreptococcus, Bulleidia, Leuconostoc were significant enriched in the persistent lymphopenia. The metabolomics analysis showed that α-Ketoisovaleric acid was increased and 7-DHCA, α-MCA, β-MCA, HCA, LCA-3S, CA, UCA and Citramalic acid were decreased in the persistent lymphopenia. ConclusionIn the process of interaction between host receptors and gut microbiota in patients with persistent lymphopenia sepsis, with a significant reduction in gut microbiota diversity and bile acid metabolites. That can affect various inflammatory pathways of gut immune cells, causing immune dysfunction in the body, which may be one of the main causes of death.

The pyruvate–GPR31 axis promotes transepithelial dendrite formation in human intestinal dendritic cells

The intestinal lumen is rich in gut microbial metabolites that serve as signaling molecules for gut immune cells. G-protein-coupled receptors (GPCRs) sense metabolites and can act as key mediators that translate gut luminal signals into host immune responses. However, the impacts of gut microbe-GPCR interactions on human physiology have not been fully elucidated. Here, we show that GPR31, which is activated by the gut bacterial metabolite pyruvate, is specifically expressed on type 1 conventional dendritic cells (cDC1s) in the lamina propria of the human intestine. Using human induced pluripotent stem cell-derived cDC1s and a monolayer human gut organoid coculture system, we show that cDC1s extend their dendrites toward pyruvate on the luminal side, forming transepithelial dendrites (TED). Accordingly, GPR31 activation via pyruvate enhances the fundamental function of cDC1 by allowing efficient uptake of gut luminal antigens, such as dietary compounds and bacterial particles through TED formation. Our results highlight the role of GPCRs in tuning the human gut immune system according to local metabolic cues.

Osteoporosis in postmenopausal women is associated with disturbances in gut microbiota and migration of peripheral immune cells

BackgroundPostmenopausal osteoporosis (PMO) results from a reduction in bone mass and microarchitectural deterioration in bone tissue due to estrogen deficiency, which may increase the incidence of fragility fractures. In recent years, the “gut-immune response-bone” axis has been proposed as a novel potential approach in the prevention and treatment of PMO. Studies on ovariectomized murine model indicated the reciprocal role of Th17 cells and Treg cells in the aetiology of osteoporosis. However, the relationship among gut microbiota, immune cells and bone metabolic indexes remains unknown in PMO.MethodsA total of 77 postmenopausal women were recruited for the study and divided into control (n = 30), osteopenia (n = 19), and osteoporosis (n = 28) groups based on their T score. The frequency of Treg and Th17 cells in lymphocytes were analyzed by flow cytometry. The serum levels of interleukin (IL)-10, 17 A, 1β, 6, tumor necrosis factor (TNF)-α, and lipopolysaccharide (LPS) were determined via enzyme-linked immunosorbent assay. Additionally, 16S rRNA gene V3-V4 region sequencing analysis was performed to investigate the gut microbiota of the participants.ResultsThe results demonstrated decreased bacterial richness and diversed intestinal composition in PMO. In addition, significant differences of relative abundance of the gut microbial community in phylum and genus levels were found, mainly including increased Bacteroidota, Proteobacteria, and Campylobacterota, as well as reduced Firmicutes, Butyricicoccus, and Faecalibacterium. Intriugingly, in the osteoporosis group, the concentration of Treg cells and associated IL-10 in peripheral circulation was negatively regulated, while other chronic systemic proinflammatory cytokines and Th17 cells showed opposite trends. Moreover, significantly elevated plasma lipopolysaccharide (LPS) in patients with osteoporosis indicated that disrupted intestinal integrity and permeability. A correlation analysis showed close relationships between gut bacteria and inflammation.ConclusionsCollectively, these observations will lead to a better understanding of the relationship among bone homeostasis, the microbiota, and circulating immune cells in PMO. The elevated LPS levels of osteoporosis patients which not only indicate a breach in intestinal integrity but also suggest a novel biomarker for assessing osteoporosis risk linked to gut health.

Dissecting causal relationships between gut microbiome, immune cells, and brain injury: A Mendelian randomization study.

Increasing literature has affirmed that changes in the gut microbiome (GM) composition were linked to distinct brain injury (BI) through the gut-brain axis, but it is uncertain if such links reflect causality. Further, the immune cell changes mediating the impact of GM on BI are not completely understood. We made use of the summary statistics of 211 GM (MiBioGen consortium), 731 immune cells, and 2 different BIs (FinnGen consortium), namely traumatic BI (TBI) and focal BI (FBI), from the extensive genome-wide association studies to date. We executed bidirectional Mendelian randomization (MR) analyses to ascertain the causal relationships between the GM and BI, and 2-step MR to validate possible mediating immune cells. Additionally, thorough sensitivity analyses verified the heterogeneity, robustness, as well as horizontal pleiotropy of the results. Based on the results of inverse-variance weighted (IVW) and sensitivity analyses, in MR analyses, 5 specific GM taxa and 6 specific GM taxa were causally associated with FBI and TBI, respectively; 27 immunophenotypes and 39 immunophenotypes were causally associated with FBI and TBI, respectively. Remarkably, Anaerofilum, LachnospiraceaeNC2004group, RuminococcaceaeUCG004, CCR2 on myeloid dendritic cell (DC), CD123 on CD62L+ plasmacytoid DC, and CD123 on plasmacytoid DC were causally associated with TBI and FBI (all P < .040). However, our reverse MR did not indicate any influence of TBI and FBI on the specific GM. In mediation analysis, we found that the associations between Escherichia.Shigella and FBI were mediated by CD123 on CD62L + plasmacytoid DC in addition to CD123 on plasmacytoid DC, each accounting for 4.21% and 4.21%; the association between FamilyXIIIAD3011group and TBI was mediated by CCR2 on myeloid DC, with mediated proportions of 5.07%. No remarkable horizontal pleiotropy or heterogeneity of instrumental variables was detected. Our comprehensive MR analysis first provides insight into potential causal links between several specific GM taxa with FBI/TBI. Additionally, CD123 on plasmacytoid DC in conjunction with CCR2 on myeloid DC may function in gut microbiota-host crosstalk in FBI and TBI, correspondingly. Further studies are critical to unravel the underlying mechanisms of the links between GM and BI.

Effects of parenteral nutrition supplemented with beta-hydroxy-beta-methylbutyrate on gut-associated lymphoid tissue and morphology in mice.

Parenteral nutrition (PN) without enteral nutrition (EN) leads to marked atrophy of gut-associated lymphoid tissue (GALT), causing mucosal defense failure in both the gut and the extraintestinal mucosal system. We evaluated the effects of beta-hydroxy-beta-methylbutyrate (HMB) on GALT and gut morphology in PN-fed mice. Experiment 1: male Institute of Cancer Research mice were assigned to the Chow (n = 12), Control (standard PN: n = 10), or H600 and H2000 (PN containing 600 mg/kg or H2000 mg/kg body weight of Ca-HMB: n = 12 and 10, respectively) groups. After 5 days of dietary manipulation, all mice were killed and the whole small intestine was harvested. GALT lymphocyte cell numbers and phenotypes of Peyer patch (PP), intraepithelial space, and lamina propria lymphocytes were evaluated. Experiment 2: 47 mice (Chow: n = 12; Control: n = 14; H600: n = 11; and H2000: n = 10) were fed for 5 days as in experiment 1. Proliferation and apoptosis of gut immune cells and mucosa, and protein expressions (mammalian target of rapamycin [mTOR], caspase-3, and Bcl2) were evaluated in the small intestine. Compared with the Controls, the Chow and HMB groups showed significantly higher PP cell numbers, prevented gut mucosal atrophy, inhibited apoptosis of gut cells, and increased their proliferation in association with increased mTOR activity and Bcl2 expression. HMB-supplemented PN is a potentially novel method of preserving GALT mass and gut morphology in the absence of EN.

Causal effects of gut microbiota, metabolites, immune cells, liposomes, and inflammatory proteins on anorexia nervosa: A mediation joint multi-omics Mendelian randomization analysis

Causal effects of gut microbiota, metabolites, immune cells, liposomes, and inflammatory proteins on anorexia nervosa: A mediation joint multi-omics Mendelian randomization analysis