Diversity Of Intestinal Microbiome Research Articles

GSK3β Substrate-competitive Inhibitors Regulate the gut Homeostasis and Barrier Function to Inhibit Neuroinflammation in Scopolamine-induced Alzheimer's Disease Model Mice.

Alzheimer's disease (AD) is a neurodegenerative disease mainly characterized by cognitive impairment. Glycogen synthase kinase 3 (GSK3β) is a potential therapeutic target against AD. Isoorientin (ISO), a GSK3β substrate competitive inhibitor, plays anti-AD effects in in vitro and in vivo AD model. TFGF-18 is an ISO synthetic analog with improved potency, but its neuroprotective effect in vivo remains to be elucidated, and the underlying mechanisms of GSK3β inhibitor against AD need to be clarified. This study investigated the TFGF-18 and ISO effects on gut homeostasis and neuroinflammation in scopolamine (SCOP)-induced AD mice. And the protection on barrier function was observed in in vitro blood-brain barrier (BBB) model of mouse brain microvascular endothelial cells (bEnd.3). The results show that TFGF-18 and ISO improved cognitive function in SCOP-induced mice, and inhibited cholinergic system disorders and inflammation in the brain and intestine, decreased the level of lipopolysaccharides (LPS) in serum and intestine, protected the diversity and balance of intestinal microbiome, increased the expressions of tight junction protein (ZO-1, occludin), brain derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GDNF) in the mouse brain and intestine. In addition, TFGF-18 and ISO protected against barrier damage in LPS-stimulated BBB model of bEnd.3 cells in vitro. TFGF-18 and ISO increased the ratio of p-GSK3β/GSK3β, suppressed toll-like receptors 4 (TLR-4) expression and nuclear factor kappa-B (NF-κB) activation in vivo and in vitro, and increased the expressions of β-catenin, nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in vitro. In conclusion, The GSK3β inhibitors TFGF-18 and ISO modulate the gut homeostasis and barrier function to inhibit neuroinflammation and attenuate cognitive impairment by regulating NF-κB, β-catenin and Nrf2/HO-1 pathways.

Effects of dietary fermented attachments of suspension cage as a replacement for sea mud on growth and intestinal health of sea cucumber Apostichopus japonicus

In the suspension cage culture process, regular cleaning to remove epiphytic organisms from the cage is essential to prevent economic losses due to the sinking of the cage. However, after cleaning, many of attachments from the suspension cage accumulate in the tidal flats, causing environmental pollution and resource wastage. Moreover, because sea cucumbers (Apostichopus japonicus) are sedimentary food organisms, sea mud is typically added to their feed to varying degrees. However, long-term excavation of sea mud can destroy the marine environment. Therefore, developing an alternative new raw feed material to replace sea mud in sea cucumber feed is necessary to promote sustainable development of the A. japonicus aquaculture industry. The aim of this study was to explore the feasibility of using fermented attachments of suspension cage (FASC) as a raw feed material for A. japonicus. Different FASC concentrations (0, 25, 50, 75, and 100 %) were used in A. japonicus feed for 60 d. Replacing Sea mud with 100 % FASC significantly improved sea cucumber growth, reduced the feed coefficient, significantly increased the activity of intestinal digestive enzymes, improved intestinal structure, and enriched intestinal microbiome diversity. Furthermore, expressions of growth genes mapk-7 and fgfr-1 significantly increased in the 100 % FASC treatment compared with that in the control, and that of negative growth regulator gene gdf-8 was inhibited. The results suggested the potential of FASC as a new raw feed material for A. japonicus.

Metagenomic dissection of the intestinal microbiome in the giant river prawn Macrobrachium rosenbergii infected with Decapod iridescent virus 1

Microbiome in the intestines of aquatic invertebrates plays pivotal roles in maintaining intestinal homeostasis, especially when the host is exposed to pathogen invasion. Decapod iridescent virus 1 (DIV1) is a devastating virus seriously affecting the productivity and success of crustacean aquaculture. In this study, a metagenomic analysis was conducted to investigate the genomic sequences, community structure and functional characteristics of the intestinal microbiome in the giant river prawn Macrobrachiumrosenbergii infected with DIV1. The results showed that DIV1 infection could significantly reduce the diversity and richness of intestinal microbiome. Proteobacteria represented the largest taxon at the phylum level, and at the species level, the abundance of Gonapodya prolifera and Solemya velum gill symbiont increased significantly following DIV1 infection. In the infected prawns, four metabolic pathways related to purine metabolism, pyrimidine metabolism, glycerophospholipid metabolism, and pentose phosphate pathway, and five pathways related to nucleotide excision repair, homologous recombination, mismatch repair, base excision repair, and DNA replication were significantly enriched. Moreover, several immune response related pathways, such as shigellosis, bacterial invasion of epithelial cells, Salmonella infection, and Vibrio cholerae infection were repressed, indicating that secondary infection in M. rosenbergii may be inhibited via the suppression of these immune related pathways. DIV1 infection led to the induction of microbial carbohydrate enzymes such as the glycoside hydrolases (GHs), and reduced the abundance and number of antibiotic-resistant ontologies (AROs). A variety of AROs were identified from the microbiota, and mdtF and lrfA appeared as the dominant genes in the detected AROs. In addition, antibiotic efflux, antibiotic inactivation, and antibiotic target alteration were the main antibiotic resistance mechanisms. Collectively, the data would enable a deeper understanding of the molecular response of intestinal microbiota to DIV1, and offer more insights into its roles in prawn resistance to DIVI infection.

Diet composition and sterilization modifies intestinal microbiome diversity and burden of Theiler's virus infection-induced acute seizures.

Brain infection with Theiler's murine encephalomyelitis virus (TMEV) in C57BL/6J mice can induce acquired epileptogenesis. Diet alters acute seizure incidence in TMEV-infected mice; yet it is unclear whether intestinal dysbiosis may also impact acute or chronic behavioral comorbidities. This study thus assessed the impact of diet formulation and sterilization on acute seizure presentation, gut microbiome composition, and epilepsy-related chronic behavioral comorbidities. Baseline fecal samples were collected from male C57BL/6J mice (4- to 5-weeks-old; Jackson Labs) upon facility arrival. Mice were randomized to either autoclaved (AC) or irradiated diet (IR) (Prolab RMH 3000) or IR (Picolab 5053). Three days later, mice underwent intracerebral TMEV or phosphate-buffered saline (PBS) injection. Fecal samples were collected from a subset of mice at infection (Day 0) and Day 7 post-infection. Epilepsy-related working memory deficits and seizure threshold were assessed 6 weeks post-infection. Gut microbiome diversity was determined by 16S rRNA amplicon sequencing of fecal samples. TMEV-infected mice displayed acute handling-induced seizures, regardless of diet: 28 of 57 IR Picolab 5053 (49.1%), 30 of 41 IR Prolab RMH 3000 (73.2%), and 47 of 77 AC Prolab RMH 3000 (61%) mice displayed seizures. The number of observed seizures differed significantly by diet: IR Picolab 5053 diet-fed mice had 2.2 ± 2.8 seizures (mean ± standard deviation), IR Prolab RMH 3000 diet-fed mice had 3.5 ± 2.9 seizures, and AC Prolab RMH 3000 diet-fed mice had 4.4 ± 3.8 seizures during the 7-day monitoring period. Gut microbiome composition differed significantly in TMEV-infected mice fed the AC Prolab RMH 3000 diet, with measured differences in gram-positive bacteria. These mice also displayed worsened long-term working memory deficits. Diet-induced differences in intestinal dysbiosis in the TMEV model are associated with marked changes in acute seizure presentation, symptomatic recovery, and onset of chronic behavioral comorbidities of epilepsy. Our study reveals a novel disease-modifying impact of dietary manipulation on intestinal bacterial species after TMEV-induced acute seizures.

Strain specific differences in vitamin D3 response: impact on gut homeostasis.

Vitamin D3 regulates a variety of biological processes irrespective of its well-known importance for calcium metabolism. Epidemiological and animal studies indicate a role in immune regulation, intestinal barrier function and microbiome diversity. Here, we analyzed the impact of different vitamin D3- containing diets on C57BL/6 and BALB/c mice, with a particular focus on gut homeostasis and also investigated effects on immune cells in vitro. Weak regulatory effects were detected on murine T cells. By trend, the active vitamin D3 metabolite 1,25-dihydroxyvitamin D3 suppressed IFN, GM-CSF and IL-10 cytokine secretion in T cells of C57BL/6 but not BALB/c mice, respectively. Using different vitamin D3-fortified diets, we found a tissue-specific enrichment of mainly CD11b+ myeloid cells but not T cells in both mouse strains e.g. in spleen and Peyer's Patches. Mucin Reg3γ and Batf expression, as well as important proteins for gut homeostasis, were significantly suppressed in the small intestine of C57BL76 but not BALB/c mice fed with a high-vitamin D3 containing diet. Differences between both mouse stains were not completely explained by differences in vitamin D3 receptor expression which was strongly expressed in epithelial cells of both strains. Finally, we analyzed gut microbiome and again an impact of vitamin D3 was detected in C57BL76 but not BALB/c. Our data suggest strain-specific differences in vitamin D3 responsiveness under steady state conditions which may have important implications when choosing a murine disease model to study vitamin D3 effects.

Longitudinal profiling of the intestinal microbiome in children with cystic fibrosis treated with elexacaftor-tezacaftor-ivacaftor.

The intestinal microbiome influences growth and disease progression in children with cystic fibrosis (CF). Elexacaftor-tezacaftor-ivacaftor (ELX/TEZ/IVA), the newest pharmaceutical modulator for CF, restores the function of the pathogenic mutated CF transmembrane conductance regulator (CFTR) channel. We performed a single-center longitudinal analysis of the effect of ELX/TEZ/IVA on the intestinal microbiome, intestinal inflammation, and clinical parameters in children with CF. Following ELX/TEZ/IVA, children with CF had significant improvements in body mass index and percent predicted forced expiratory volume in one second, and required fewer antibiotics for respiratory infections. Intestinal microbiome diversity increased following ELX/TEZ/IVA coupled with a decrease in the intestinal carriage of Staphylococcus aureus, the predominant respiratory pathogen in children with CF. There was a reduced abundance of microbiome-encoded antibiotic resistance genes. Microbial pathways for aerobic respiration were reduced after ELX/TEZ/IVA. The abundance of microbial acid tolerance genes was reduced, indicating microbial adaptation to increased CFTR function. In all, this study represents the first comprehensive analysis of the intestinal microbiome in children with CF receiving ELX/TEZ/IVA.IMPORTANCECystic fibrosis (CF) is an autosomal recessive disease with significant gastrointestinal symptoms in addition to pulmonary complications. Recently approved treatments for CF, CF transmembrane conductance regulator (CFTR) modulators, are anticipated to substantially improve the care of people with CF and extend their lifespans. Prior work has shown that the intestinal microbiome correlates with health outcomes in CF, particularly in children. Here, we study the intestinal microbiome of children with CF before and after the CFTR modulator, ELX/TEZ/IVA. We identify promising improvements in microbiome diversity, reduced measures of intestinal inflammation, and reduced antibiotic resistance genes. We present specific bacterial taxa and protein groups which change following ELX/TEZ/IVA. These results will inform future mechanistic studies to understand the microbial improvements associated with CFTR modulator treatment. This study demonstrates how the microbiome can change in response to a targeted medication that corrects a genetic disease.

Fecal metabolite profiling identifies liver transplant recipients at risk for postoperative infection

Metabolites produced by the intestinal microbiome modulate mucosal immune defenses and optimize epithelial barrier function. Intestinal dysbiosis, including loss of intestinal microbiome diversity and expansion of antibiotic-resistant pathobionts, is accompanied by changes in fecal metabolite concentrations and increased incidence of systemic infection. Laboratory tests that quantify intestinal dysbiosis, however, have yet to be incorporated into clinical practice. We quantified fecal metabolites in 107 patients undergoing liver transplantation (LT) and correlated these with fecal microbiome compositions, pathobiont expansion, and postoperative infections. Consistent with experimental studies implicating microbiome-derived metabolites with host-mediated antimicrobial defenses, reduced fecal concentrations of short- and branched-chain fatty acids, secondary bile acids, and tryptophan metabolites correlate with compositional microbiome dysbiosis in LT patients and the relative risk of postoperative infection. Our findings demonstrate that fecal metabolite profiling can identify LT patients at increased risk of postoperative infection and may provide guideposts for microbiome-targeted therapies.

Analysis on Changes and Influencing Factors of the Intestinal Microbiota of Alpine Musk Deer between the Place of Origin and Migration.

In China, the population of wild musk deer, belonging to the family Moschidae, has drastically decreased in recent years owing to human activities and environmental changes. During the 1990s, artificial breeding of Alpine musk deer was conducted in Xinglong Mountain, Gansu Province, China, and their ex situ conservation was explored for over a decade. Ex situ protection is beneficial for expanding the population of animals and maintaining their genetic diversity; however, it can also induce metabolic diseases and parasitic infections and reduce reproductive capacity. The gut microbiota of animals has a considerable impact on host energy metabolism and immune regulation, thereby playing a crucial role in the overall health and reproductive success of the host. In this study, by comparing the differences in the intestinal microbiome of the musk deer according to their place of origin and migration, the changes in their gut microbiota and the influencing factors were explored to provide a theoretical basis for monitoring the health status of the musk deer. We used 16S rRNA high-throughput sequencing technology to analyze the structure and diversity of the gut microbiota of Alpine musk deer in Gansu (G, place of origin) and Sichuan (S, place of migration). The results showed that the dominant bacteria and genera in the intestinal microbiome of captive musk deer were similar in the places of origin and migration, but significant differences were observed in their relative abundance (p < 0.05). Regarding Firmicutes and Actinobacteria, which are related to plant cellulose digestion, the relative abundance in group G was higher than that in group S; regarding Proteobacteria and Verrucomicrobia, which are related to fat and starch intake, the relative abundance in group S was higher than that in group G; the relative abundance of Bacillus and Clostridium sensu stricto, which are related to fiber digestibility, was higher in group G than in group S; the relative abundance of conditional pathogens Acinetobacter and Escherichia-Shigella was higher in group S than in group G. The results of α and β diversity analysis also showed significant differences between the two groups (p < 0.05). The ACE and Shannon indices of musk deer in group G were considerably higher than those in group S, and the Simpson index of musk deer in group S was greater than that in group G, indicating that the abundance and diversity of intestinal microbiome were higher in musk deer of Gansu than those of Sichuan. Comparison of the changes in the intestinal microbiome of the musk deer according to the place of origin and migration showed that the plant cellulose content in the food of the musk deer, the fat content in the concentrated feed, and changes in the feeding environment have an impact on the intestinal microbiome. Effective monitoring of the health and immunity of the musk deer is crucial for ensuring their overall health, which in turn will aid in formulating a scientific and reasonable management plan for their conservation.

Sex-specific intestinal dysbiosis persists after multicompartmental injury

BackgroundPreclinical studies of the gut microbiome after severe traumatic injury have demonstrated severe dysbiosis in males, with sex-specific microbial differences up to 2 days after injury. However, the impact of host sex on injury-driven dysbiosis over time remains unknown. We hypothesized that sex-specific differences in intestinal microbiome diversity and composition after traumatic injury with and without stress would persist after 7 days. MethodsMale and proestrus female Sprague-Dawley rats (n = 8/group) were subjected to either polytrauma (lung contusion, hemorrhagic shock, cecectomy, bifemoral pseudofractures), polytrauma plus chronic restraint stress, or naïve controls. The fecal microbiome was measured on days 0, 3, and 7 using 16S rRNA sequencing and Quantitative Insights into Microbial Ecology bioinformatics analyses. Microbial alpha-diversity (Chao1 and Shannon indices) and beta-diversity were assessed. Analyses were performed in GraphPad and “R,” with significance defined as P < .05. ResultsPolytrauma and polytrauma plus chronic restraint stress reduced alpha-diversity (Chao1, Shannon) within 3 days postinjury, which persisted up to day 7 in both sexes; polytrauma and polytrauma plus chronic restraint stress females had significantly decreased Chao1 compared to male counterparts at day 7 (P = .02). At day 7, the microbiome composition in polytrauma females had higher proportion of Mucispirillum, whereas polytrauma plus chronic restraint stress males demonstrated elevated abundance of Ruminococcus and Akkermansia. ConclusionMulticompartmental trauma induces intestinal dysbiosis that is sex-specific with persistence of decreased diversity and unique “pathobiome” signatures in females after 1 week. These findings underline sex as an important biological variable that may influence variable host-specific responses and outcomes after severe trauma and critical illness. This underscores the need to consider precision medicine strategies to ameliorate these outcomes.

Metagenomic sequencing reveals altered gut microbial compositions and gene functions in patients with non-segmental vitiligo

BackgroundVitiligo has been correlated with an abnormal gut microbiota. We aimed to systematically identify characteristics of the gut microbial compositions, genetic functions, and potential metabolic features in patients with non-segmental vitiligo.MethodsTwenty-five patients with non-segmental vitiligo and 25 matched healthy controls (HCs) were enrolled. Metagenomic sequencing and bioinformatic analysis were performed to determine the gut microbiota profiles. Differences in gut microbiota diversity and composition between patients with vitiligo and HCs were analyzed. Gene functions and gut metabolic modules were predicted with the Kyoto Encyclopedia of Gene and Genomes (KEGG) and MetaCyc databases.ResultsCompared with HCs, alpha diversity of intestinal microbiome in vitiligo patients was significantly reduced. At the species level, the relative abundance of Staphylococcus thermophiles was decreased, and that of Bacteroides fragilis was increased in patients with vitiligo compared with those of the HCs. Linear discriminant analysis (LDA) effect size (LEfSe) analysis revealed representative microbial markers of Lachnospiraceae_bacterium_BX3, Massilioclostridium_coli, TM7_phylum_sp_oral_taxon_348 and Bacteroides_fragilis for patients with vitiligo. KEGG gene function analysis showed that the NOD-like receptor signaling pathway was significantly enriched in patients with vitiligo. Gut metabolic modules (GMMs) analysis showed that cysteine degradation was significantly down-regulated, and galactose degradation was up-regulated in patients with vitiligo. A panel of 28 microbial features was constructed to distinguish patients with vitiligo from HCs.ConclusionsThe gut microbial profiles and genetic functions of patients with vitiligo were distinct from those of the HCs. The identified gut microbial markers may potentially be used for earlier diagnosis and treatment targets.

Nurture outpaces nature: fostering with an attentive mother alters social dominance in a mouse model of stress sensitivity.

Maternal care is critical for epigenetic programming during postnatal brain development. Stress is recognized as a critical factor that may affect maternal behavior, yet owing to high heterogeneity in stress response, its impact varies among individuals. We aimed here to understand the connection between inborn stress vulnerability, maternal care, and early epigenetic programming using mouse populations that exhibit opposite poles of the behavioral spectrum (social dominance [Dom] and submissiveness [Sub]) and differential response to stress. In contrast to stress-resilient Dom dams, stress-vulnerable Sub dams exhibit significantly lower maternal attachment, serum oxytocin, and colonic Lactobacillus reuteri populations. Sub offspring showed a reduced hippocampal expression of key methylation genes at postnatal day (PND) 7 and a lack of developmentally-dependent increase in 5-methylcytosine (5-mC) at PND 21. In addition, Sub pups exhibit significant hypermethylation of gene promoters connected with glutamatergic synapses and behavioral responses. We were able to reverse the submissive endophenotype through cross-fostering Sub pups with Dom dams (Sub/D). Thus, Sub/D pups exhibited elevated hippocampal expression of DNMT3A at PND 7 and increased 5-mC levels at PND 21. Furthermore, adult Sub/D offspring exhibited increased sociability, social dominance, and hippocampal glutamate and monoamine levels resembling the neurochemical profile of Dom mice. We postulate that maternal inborn stress vulnerability governs epigenetic patterning sculpted by maternal care and intestinal microbiome diversity during early developmental stages and shapes the array of gene expression patterns that may dictate neuronal architecture with a long-lasting impact on stress sensitivity and the social behavior of offspring.

Identification of colorectal cancer progression-associated intestinal microbiome and predictive signature construction

ObjectiveThe relationship between intestinal microbiome and colorectal cancer (CRC) progression is unclear. This study aims to identify the intestinal microbiome associated with CRC progression and construct predictive labels to support the accurate assessment and treatment of CRC.MethodThe 192 patients included in the study were divided into stage I-II and stage III-IV CRC patients according to the pathological stages, and preoperative stools were collected from both groups for 16S rDNA sequencing of the intestinal microbiota. Pearson correlation and Spearman correlation coefficient analysis were used to analyze the differential intestinal microbiome and the correlation with tumor microenvironment and to predict the functional pathway. XGBoost model (XGB) and Random Forest model (RF) were used to construct the microbiome-based signature. The total RNA extraction from 17 CRC tumor simples was used for transcriptome sequencing.ResultThe Simpson index of intestinal microbiome in stage III-IV CRC were significantly lower than those in stage I-II CRC. Proteus, Parabacteroides, Alistipes and Ruminococcus etc. are significantly enriched genus in feces of CRC patients with stage III-IV. ko00514: Other types of O − glycan biosynthesis pathway is relevant with CRC progression. Alistipes indistinctus was positively correlated with mast cells, immune activators IL-6 and IL6R, and GOBP_PROTEIN_FOLDING_IN_ENDOPLASMIC_RETICULUM dominantly. The Random Forest (RF) model and eXtreme Gradient Boosting (XGBoost) model constructed with 42 CRC progression-associated differential bacteria were effective in distinguishing CRC patients between stage I-II and stage III-IV.ConclusionsThe abundance and diversity of intestinal microbiome may increase gradually with the occurrence and progression of CRC. Elevated fetal abundance of Proteus, Parabacteroides, Alistipes and Ruminococcus may contribute to CRC progression. Enhanced synthesis of O − glycans may result in CRC progression. Alistipes indistinctus may play a facilitated role in mast cell maturation by boosting IL-6 production. Alistipes indistinctus may work in the correct folding of endoplasmic reticulum proteins in CRC, reducing ER stress and prompting the survival and deterioration of CRC, which may owe to the enhanced PERK expression and activation of downstream UPR by Alistipes indistinctus. The CRC progression-associated differential intestinal microbiome identified in our study can be served as potential microbial markers for CRC staging prediction.

Characterization of microbiota and secretory Ig-A in the domestic duck (Anas platyrhynchos) small and large intestine

Abstract. Susanti R, Utami NR, Yuniastuti A. 2023. Characterization of microbiota and secretory Ig-A in the domestic duck (Anas platyrhynchos)small and large intestine. Biodiversitas 24: 2458-2466. The Microbiome composition could affect the duck's intestines' microenvironment, which may shape the microstructure's anatomy, metabolism, and immune system. Therefore, this study aims to characterize the intestinal microbiome's abundance, diversity, and IgA distribution in ducks' intestines. This study took 15 healthy domestic ducks (Anas platyrhynchosLinnaeus, 1758) from an intensive duck farm in Central Java, Indonesia. Five grams of each small and large intestine content were collected aseptically for metagenomic analysis. Then, the intestine organs were taken for immunohistochemistry preparations to depict the IgA distribution. The results showed that the small intestine has a greater bacterial abundance community, with 18 phyla, while only 13 are found in the large intestine. Interestingly, three phyla: Firmicutes, Actinobacteria, and Bacteroidetes, were found dominantly in both organs. However, the comparison of Firmicutes and Bacteroidetes ratio was higher in the small intestine (2357.76) than large intestine (10.64). The IgA distribution in the small and large intestines showed intermediate staining intensity (score: 2.07-2.20) and a final Allred score of 5.0 (positive). Even though dysbiosis microbiome was present in intestines with dominant species Streptococcus and Enterococcus, it seems no significant IgA over secretion. Understanding duck's gut immune response is important because it is highly tolerant to the pathogens that make them play an important role as an environmental reservoir for pathogenic viruses and bacteria and may potentially comprehend future infectious disease outbreaks.

The association between altered intestinal microbiome, impaired systemic and ocular surface immunity, and impaired wound healing response after corneal alkaline-chemical injury in diabetic mice.

We aim to investigate the effect of sustained hyperglycemia on corneal epithelial wound healing, ocular surface and systemic immune response, and microbiome indices in diabetic mice compared to controls after alkaline chemical injury of the eye. Corneal alkaline injury was induced in the right eye of Ins2Akita (Akita) mice and wild-type mice. The groups were observed at baseline and subsequently days 0, 3, and 7 after injury. Corneal re-epithelialization was observed under slit lamp with fluorescein staining using a cobalt blue light filter. Enucleated cornea specimens were compared at baseline and after injury for changes in cornea thickness under hematoxylin and eosin staining. Tear cytokine and growth factor levels were measured using protein microarray assay and compared between groups and time points. Flow cytometry was conducted on peripheral blood and ocular surface samples to determine CD3+CD4+ cell count. Fecal samples were collected, and gut microbiota composition and diversity pattern were measured using shotgun sequencing. Akita mice had significantly delayed corneal wound healing compared to controls. This was associated with a reduction in tear levels of vascular endothelial growth factor A, angiopoietin 2, and insulin growth factor 1 on days 0, 3, and 7 after injury. Furthermore, there was a distinct lack of upregulation of peripheral blood and ocular surface CD3+CD4+ cell counts in response to injury in Akita mice compared to controls. This was associated with a reduction in intestinal microbiome diversity indices in Akita mice compared to controls after injury. Specifically, there was a lower abundance of Firmicutes bacterium M10-2 in Akita mice compared to controls after injury. In diabetic mice, impaired cornea wound healing was associated with an inability to mount systemic and local immune response to ocular chemical injury. Baseline and post-injury differences in intestinal microbial diversity and abundance patterns between diabetic mice and controls may potentially play a role in this altered response.

Updates in Prevention of Surgical Site Infection: Comment.

Long et al.1 provided a well-written and accessible review of new ideas in the field of surgical site infection prevention. Within their discussion of the patient’s microbiome, the authors touch on the potential for interactions between the patient microbiome and anesthetic agents administered perioperatively. Although they accurately identify the immunosuppressive potential of volatile anesthetics and intravenous opioids, we think that it is important to note that there exist other agents capable of producing and maintaining general anesthesia. Medications like ketamine and propofol are immunomodulatory in different ways, and thus their use may also impact the development of surgical site infections.Long et al.1 cite two mouse model articles where exposure to volatile anesthetics was associated with a decrease in intestinal microbiome diversity.2,3 In contrast, Guo et al.,4 using a rat model, looked at the effect of a continuous infusion of propofol during a 3-h period on the intestinal microbiome and found little change in the diversity of the intestinal microbiome after exposure to propofol. Similarly, Gerb et al.5 looked at the effects on the intestinal microbiome of mice after 10 daily exposures to a bolus dose of ketamine that rendered the mice unconscious for approximately 15 to 30 min per ketamine exposure and also found little change in the diversity of the intestinal microbiome.No definitive evidence exists to recommend one type of anesthetic over another. Given the minimal impact on the intestinal microbiome, it might be tempting to conclude that replacing volatile anesthetics with agents such as propofol and ketamine might decrease the incidence of surgical site infection. But there is also evidence to the contrary. For example, Visvabharathy et al.6 looked at susceptibility to infection due to exogenous bacteremia using Listeria and Staphylococcus aureus in mice receiving intravenous propofol compared to mice receiving intravenous ketamine with xylazine and found that propofol increased susceptibility to infection. In a research letter, Liu et al.7 looked at the intestinal microbiome in 21 patients undergoing nephrectomy with propofol alone compared to sevoflurane alone compared to propofol and sevoflurane combined and found that the mixed anesthetic7 was associated with the fewest perturbations.Clearly it remains premature to advocate for a total intravenous technique in the absence of more clinically robust data. Further research in animal models and in humans is needed to try and elucidate not only if there is an optimal anesthetic agent for prevention of surgical site infection, but also what the combined effects of multiple anesthetics, as routinely administered when patients present for surgery, have on the patient’s susceptibility to infection after surgery.Surgical site infections are a multidisciplinary problem. Once more data are available, it may turn out that the effects of anesthetic agents are small and of minor importance in patients with normal immune systems. But the selection of anesthetic agents is one aspect we have almost complete control over; we should be making every effort to maximize the ability of the patient’s immune system to combat infection.The authors declare no competing interests.

Accumulation of Black Carbon Particles in Placenta, Cord Blood, and Childhood Urine in Association with the Intestinal Microbiome Diversity and Composition in Four- to Six-Year-Old Children in the ENVIRONAGE Birth Cohort.

The gut microbiome plays an essential role in human health. Despite the link between air pollution exposure and various diseases, its association with the gut microbiome during susceptible life periods remains scarce. In this study, we examined the association between black carbon particles quantified in prenatal and postnatal biological matrices and bacterial richness and diversity measures, and bacterial families. A total of 85 stool samples were collected from 4- to 6-y-old children enrolled in the ENVIRonmental influence ON early AGEing birth cohort. We performed 16S rRNA gene sequencing to calculate bacterial richness and diversity indices (Chao1 richness, Shannon diversity, and Simpson diversity) and the relative abundance of bacterial families. Black carbon particles were quantified via white light generation under femtosecond pulsed laser illumination in placental tissue and cord blood, employed as prenatal exposure biomarkers, and in urine, used as a post-natal exposure biomarker. We used robust multivariable-adjusted linear models to examine the associations between quantified black carbon loads and measures of richness (Chao1 index) and diversity (Shannon and Simpson indices), adjusting for parity, season of delivery, sequencing batch, age, sex, weight and height of the child, and maternal education. Additionally, we performed a differential relative abundance analysis of bacterial families with a correction for sampling fraction bias. Results are expressed as percentage difference for a doubling in black carbon loads with 95% confidence interval (CI). Two diversity indices were negatively associated with placental black carbon [Shannon: (95% CI: , ); Simpson: (95% CI: , )], cord blood black carbon [Shannon: (95% CI: , ); Simpson: (95% CI: , )], and urinary black carbon [Shannon: (95% CI: , ); Simpson: (95% CI: , )]. The explained variance of black carbon on the above indices varied from 6.1% to 16.6%. No statistically significant associations were found between black carbon load and the Chao1 richness index. After multiple testing correction, placental black carbon was negatively associated with relative abundance of the bacterial families Defluviitaleaceae and Marinifilaceae, and urinary black carbon with Christensenellaceae and Coriobacteriaceae; associations with cord blood black carbon were not statistically significant after correction. Black carbon particles quantified in prenatal and postnatal biological matrices were associated with the composition and diversity of the childhood intestinal microbiome. These findings address the influential role of exposure to air pollution during pregnancy and early life in human health. https://doi.org/10.1289/EHP11257.

Primary source of dietary protein is correlated with differences in the intestinal microbiome diversity

In spite of the recent popularization of the vegan diet, there is currently a deficit of studies that compare the impact and associated health benefits of dietary protein source, one of the main differentiators between vegan and non-vegan diets, on the intestinal microbiome. The objective of this study was therefore to correlate observed changes in the intestinal microbiome to changes in dietary protein sources. We hypothesized that changes in dietary protein source are associated with changes in the composition of the intestinal microbiome. The participant changed their diet over four separate one-week periods to include plant proteins only, plant proteins and dairy proteins, animal proteins only, and finally animal proteins and dairy proteins. The participant followed their respective dietary treatments for one week. Bacterial 16S dual-index sequencing and bioinformatic analysis identified seven genera and two families of bacteria. Of these, Bifidobacterium, Bacteroides, Lactobacillum, and Clostridium exhibited population trends correlated with changes in diet. Moreover, a comparison of α-diversity indicated a statistically significant change over the course of the experiment. Although the results of this experiment cannot be generalized due to the sample size, the hypothesis of this experiment was validated: changes in dietary protein source are correlated with changes in the diversity of the intestinal microbiome. However, we recommend further research into the impacts of variance in dietary protein source on the microbiome, especially by implementing longer-term dietary treatments.

Fecal Microbiota Transplantation in Liver Diseases and Recent Developments

Introduction: The intestine, as an important part of the human gastrointestinal tract, provides a favorable milieu for the growth and development of a diverse and large population (approximately 1000 species) of bacteria. Currently, the presence of a cohesive relationship between intestinal bacteria and the host is being well studied and identified. According to the available scientific evidence, the establishment of conditions of imbalance (dysbiosis) in the number and diversity of intestinal microbiome causes the onset/progression of acute and chronic liver disorders (fatty liver, cirrhosis, and liver autoimmune disease). Therefore, modifying the balance and creating conditions of microbial eubiosis by fecal microbiota transplantation can be considered as a novel and host-compatible biological approach in the supportive treatment of liver diseases. Consequently, in the present study, while referring to investigations related to the focus of intestinal microbiome and their relation to liver diseases, the existing scientific evidence on the clinical efficacy of fecal microbiota transplantation in the treatment of some liver diseases and recent advances are discussed.&#x0D; Conclusion: Both basic science research and clinical studies have proven that the fecal microbiota transplantation method can effectively strengthen and improve the gut microbiota during acute and chronic liver diseases, rebuild and restore the balance of the gut microbiome, and accelerate the patient's recovery.&#x0D;

Metagenomic and metabolomic analyses show correlations between intestinal microbiome diversity and microbiome metabolites in ob/ob and ApoE-/- mice.

Obesity and atherosclerosis are the most prevalent metabolic diseases. ApoE-/- and ob/ob mice are widely used as models to study the pathogenesis of these diseases. However, how gut microbes, gut bacteriophages, and metabolites change in these two disease models is unclear. Here, we used wild-type C57BL/6J (Wt) mice as normal controls to analyze the intestinal archaea, bacteria, bacteriophages, and microbial metabolites of ob/ob and ApoE-/- mice through metagenomics and metabolomics. Analysis of the intestinal archaea showed that the abundances of Methanobrevibacter and Halolamina were significantly increased and decreased, respectively, in the ob/ob group compared with those in the Wt and ApoE-/- groups (p < 0.05). Compared with those of the Wt group, the relative abundances of the bacterial genera Enterorhabdus, Alistipes, Bacteroides, Prevotella, Rikenella, Barnesiella, Porphyromonas, Riemerella, and Bifidobacterium were significantly decreased (p < 0.05) in the ob/ob mice, and the relative abundance of Akkermansia was significantly decreased in the ApoE-/- group. The relative abundances of A. muciniphila and L. murinus were significantly decreased and increased, respectively, in the ob/ob and ApoE-/- groups compared with those of the Wt group (p < 0.05). Lactobacillus_ prophage_ Lj965 and Lactobacillus _ prophage _ Lj771 were significantly more abundant in the ob/ob mice than in the Wt mice. Analysis of the aminoacyl-tRNA biosynthesis metabolic pathway revealed that the enriched compounds of phenylalanine, glutamine, glycine, serine, methionine, valine, alanine, lysine, isoleucine, leucine, threonine, tryptophan, and tyrosine were downregulated in the ApoE-/- mice compared with those of the ob/ob mice. Aminoacyl-tRNA synthetases are considered manifestations of metabolic diseases and are closely associated with obesity, atherosclerosis, and type 2 diabetes. These data offer new insight regarding possible causes of these diseases and provide a foundation for studying the regulation of various food nutrients in metabolic disease models.

Accumulation of Black Carbon Particles in Placenta, Cord Blood and Childhood Urine on the Intestinal Microbiome Diversity and Composition in Four-to-Six-Year-Old Children

Accumulation of Black Carbon Particles in Placenta, Cord Blood and Childhood Urine on the Intestinal Microbiome Diversity and Composition in Four-to-Six-Year-Old Children