Gut microbes reports最新文献

Antibodies play an essential role in preserving intestinal homeostasis in healthy and dysbiotic states. Recent studies demonstrate that a microbiome-dependent intestine-specific complement system maintains intestinal homeostasis. Morphine induces microbial dysbiosis within hours of administration characterized by the expansion of pathogenic bacteria with a concurrent decrease in commensal bacteria. A murine model of short-term morphine treatment was used to provide insights into the early immune processes during microbial dysbiosis. Within 24 h, morphine treatment upregulates the expression of classical complement pathway genes in intestinal tissue, with a concurrent increase in the complement proteins C1q and C3 in the ileal luminal content. Importantly, a parallel increase in the concentration of complement-activating antibodies IgM and IgG is observed in the ileal luminal content at 24 h. The increased concentration of complement proteins and antibodies are dependent on the microbiome, as microbial depletion prior to morphine treatment abolishes this increase. Finally, intestinal infiltration and activation of neutrophils is observed concurrent with microbial dysbiosis. This study demonstrates rapid microbiome-dependent intestinal recruitment of complement machinery during microbial dysbiosis. Together, these data confirm the relationship between intestinal complement and the microbiome and shows that the classical complement system is activated to protect the host during microbial dysbiosis.

Myeloperoxidase (MPO), predominantly expressed in neutrophils, catalyzes the production of hypochlorous acid (HOCl) that plays an integral role in the host defense against invading pathogens. However, little is known about its role in maintaining normal gut microbiome and function. Here, we report the comparisons of inflammation and microbiome in the intestines of WT and MPO^-/- mice. Immune cell profiling demonstrated that the MPO^-/- mice had significantly more neutrophils and T cells in their intestinal mucosae and significantly more fecal calprotectin as compared to the WT mice. Fluorescent dextran permeability of the bowel showed no difference between the two strains of mice. Carmine Red transit demonstrated that the MPO^-/- intestines had slower movements than did the WT controls. Sequencing the intestinal 16S rDNA of co-housed MPO^-/- and WT mice identified 13 bacterial families, 2 of which were unique to MPO^-/- and 7 to WT mice. Alpha diversity of the microbiome in WT intestines was significantly higher than that of MPO^-/- ones, and beta diversity of the two microbial communities of the two genotypes also differed significantly. Functional pathway analyses revealed distinct metabolic signatures. Thus, normal MPO function is important to intestinal health and its deficiency leads to gut inflammation and dysbiosis.

Cesarean section delivery is associated with altered early-life bacterial colonization and later adverse inflammatory outcomes. Although gut bacteriophages can alter the gut microbiome and host responses, little is known about how delivery mode impacts bacteriophage colonization over time. Therefore, we conducted shotgun metagenomic sequencing on serial stool samples from infants from birth to 24 months of age. 60% of infants were born by vaginal delivery. 94% of the DNA viral sequences identified were bacteriophages. Virome alpha diversity was increased in vaginally delivered infants at 2 months (p=0.004). Beta diversity differed by delivery mode up to 12 months when stratified by peripartum antibiotic use (p<0.05). Predicted bacteriophage hosts differed by delivery mode (Q <0.1) up to 24 months. Moreover, predicted bacteriophage functional genes differed by delivery mode up to 24 months. There was a higher abundance of viral auxiliary metabolic genes associated with host responses in vaginal delivery at early timepoints. Clear differences in bacteriophage composition and function by delivery mode were seen in early life. Given that bacteriophages are known to affect immune responses, our results suggest that future investigation into how delivery mode leads to adverse inflammatory outcomes should also include the potential role of bacteriophages and transkingdom interactions.

Non-steroidal anti-inflammatory drug (NSAID)-induced toxicities are a significant clinical problem, yet the factors influencing these outcomes remain incompletely understood. Here, we investigated the impact of mouse vendor on indomethacin-induced injury using C57BL/6 mice from different breeding facilities (in-house "Tar Heel" and commercial Charles River). We found that Tar Heel mice exhibited significantly enhanced susceptibility to indomethacin toxicity, characterized by greater body weight loss, increased ileal ulceration, elevated fecal lipocalin-2 levels, and higher goblet cell numbers in ileum compared to Charles River mice. Importantly, whole genome metagenomic analysis revealed distinct baseline gut microbiomes between the two types of mice. Notably, Tar Heel mice showed higher abundances of β-glucuronidase (GUS)-producing bacteria, particularly those expressing Loop-1 GUS enzymes, and elevated levels of mucolytic enzyme-encoding bacteria. These differences suggest that enhanced indomethacin toxicity observed in Tar Heel mice may be related to functional changes in their gut microbiome, which may predispose to an exaggerated response to NSAID exposure. Together, our findings demonstrate that vendor-specific differences significantly influence NSAID-induced intestinal toxicity and highlight the importance of considering mouse sources and gut microbial compositions in experimental design. Moreover, we highlight potential functional roles that gut microbes play in host-indomethacin interactions.

Metabolites from gut microbes have a wide range of functions within the host body. One important function of these metabolites is to either positively or negatively control CD8⁺ cytotoxic T lymphocytes (CTLs), which can kill cancer and virus-infected cells. In healthy conditions, gut microbes produce a mixture of metabolites that promote CTL activity but also suppress excessive inflammatory responses. However, gut microbial dysbiosis occurs in patients with cancer, and this leads to changes in the production of gut microbial metabolites that can suppress CTL activity, promote inflammatory responses, and/or aid cancer growth. Decreased levels of CTL-promoting metabolites such as short-chain fatty acids, indole metabolites and polyamines but increased levels of CTL-suppressing metabolites, such as certain bile acids along with oncogenic metabolites, have been observed in patients with cancer. This review summarizes the altered production of major microbial metabolites in patients with cancer and discusses the impact of these changes on anti-cancer CTL responses.

The microbiome, a complex micro-ecosystem, helps the host with various vital physiological processes. Alterations of the microbiome (dysbiosis) have been linked with several diseases, and generally, differential abundance testing between the healthy and patient groups is performed to identify important bacteria. However, providing a singular species of bacteria to an individual as treatment has not been as successful as fecal microbiota transplant therapy, where the entire microbiome of a healthy individual is transferred. These observations suggest that a combination of bacteria might be crucial for the beneficial effects. Here we provide the framework to utilize topic modeling, an unsupervised machine learning approach, to identify a community of bacteria related to health or disease. Specifically, we used our previously published gut microbiome data of patients with multiple sclerosis (MS), a neurodegenerative disease linked to a dysbiotic gut microbiome. We identified communities of bacteria associated with MS, including genera previously discovered, but also others that would have been overlooked by differential abundance testing. This method can be a useful tool for analyzing the microbiome, and it should be considered along with the commonly utilized differential abundance tests to better understand the role of the gut microbiome in health and disease.