Hepatocellular carcinoma (HCC) has an extremely poor prognosis due to the development of chemoresistance, coupled with inherently increased stemness properties. Long non-coding RNAs (LncRNAs) are key regulators for tumor cell stemness and chemosensitivity. Currently the relevance between LINC00680 and tumor progression was still largely unknown, with only one study showing its significance in glioblastoma. The study herein was aimed at identifying the role of LINC00680 in the regulation HCC stemness and chemosensitivity.

Increasing evidence has revealed a close correlation between cancerous inhibitor of protein phosphatase 2A (CIP2A) and cancer progression. CIP2A has been shown to participate in diverse biological processes, such as development, tumorigenic transformation and chemoresistance. However, the functions of CIP2A in colorectal cancer (CRC) and its underlying mechanisms of action are not yet completely understood. The purpose of this study was to explore its clinical significance, function and relevant pathways in CRC.

Patients with Rett syndrome suffer from a loss-of-function mutation of the Mecp2 gene, which results in various symptoms including autistic traits and motor deficits. Deletion of Mecp2 in the brain mimics part of these symptoms, but the specific function of methyl-CpG-binding protein 2 (MeCP2) in the cerebellum remains to be elucidated. Here, we demonstrate that Mecp2 deletion in Purkinje cells (PCs) reduces their intrinsic excitability through a signaling pathway comprising the small-conductance calcium-activated potassium channel PTP1B and TrkB, the receptor of brain-derived neurotrophic factor. Aberration of this cascade, in turn, leads to autistic-like behaviors as well as reduced vestibulocerebellar motor learning. Interestingly, increasing activity of TrkB in PCs is sufficient to rescue PC dysfunction and abnormal motor and non-motor behaviors caused by Mecp2 deficiency. Our findings highlight how PC dysfunction may contribute to Rett syndrome, providing insight into the underlying mechanism and paving the way for rational therapeutic designs.

The decrease in ovarian hormone secretion that occurs during menopause results in an increase in body weight and adipose tissue mass. Probiotics and soy isoflavones (SIFs) could affect the gut microbiota and exert anti-obesity effects. The objective of this study was to investigate the effects of probiotics and a diet containing SIF (SIF diet) on ovariectomized mice with menopausal obesity, including the gut microbiome. The results demonstrate that Bifidobacterium longum 15M1 can reverse menopausal obesity, whilst the combination of Lactobacillus plantarum 30M5 and a SIF diet was more effective in alleviating menopausal lipid metabolism disorder than either components alone. Probiotics and SIFs play different anti-obesity roles in menopausal mice. Furthermore, 30M5 alters the metabolites of the gut microbiota that increase the circulating estrogen level, upregulates the expression of estrogen receptor α in abdominal adipose tissue and improves the production of short-chain fatty acids (SCFAs). A SIF diet can significantly alter the structure of the fecal bacterial community and enrich the pathways related to SCFAs production. Moreover, 30M5 and a SIF diet acted synergistically to effectively resolve abnormal serum lipid levels in ovariectomized mice, and these effects appear to be associated with regulation of the diversity and structure of the intestinal microbiota to enhance SCFAs production and promote estrogen circulation.

The gut microbiota in sows is important for the health of the host, and potential benefits may also be transferred to piglets during pregnancy. Therefore, systematic studies investigating the changes in the gut microbiota of sows are needed to elucidate the microbial compositions and functions. This study was conducted at 12 time points to investigate the temporal variations in gut microbiota on Days 27, 46, 64, 81, 100, and 113 during gestation (G) and Days 3, 5, 7, 10, 14, and 21 during lactation (L). Results suggested that the gut microbiota changed across the perinatal period with microbial function and abundance varying between the prenatal and postnatal periods. The alpha diversity was higher in the postnatal period than in the prenatal period. Thirty-eight genera were distributed between the two periods with Methanobrevibacter, Desulfovibrio, Akkermansia, and Turicibacter being enriched in the prenatal period while Eubacterium, Actinobacillus, Paludibacter, Butyricimonas, Megasphaera, Succiniclasticum, Acidaminococcus, and Rummeliibacillus were enriched in the postnatal period. Analysis done at the different time points of the prenatal period suggested that Days 27 and 113 had more microbial biomarkers than other days. Bacteroidales, Bacteroidia, and Prevotella were enriched on the 27th day, while bacteria belonging to the Clostridium and Ruminococcaceae were enriched on the 113th day. On the other hand, Clostridiales, Ruminococcaceae, Clostridia, and unclassified Christensenellaceae were enriched three days after delivery. Predicted microbial KO functions were also more enriched on Day 27 of the gestation period and Day 3 of the lactation period. Random forest, a machine learning method, was used to identify the top five important genera of Megasphaera, Stenotrophomonas, Phyllobacterium, Catenibacterium, and Turicibacter, while the most important function was arginine and proline metabolism. These systematic results provide important information for the gut microbiota of sows.

of Background Data: Depression is one of the most common comorbidities in patients with chronic low back pain. However, the mechanisms of depression in chronic low back pain patients and the effect of antidepressants on the comorbidity of pain and depression need to be further explored. The establishment of the appropriate animal models and of more effective therapies is critical for this comorbidity. Lumbar disc herniation (LDH) is the most common disease that causes low back pain. The current study examined whether an LDH model shows behavioral and biochemical alterations that are in accordance with the characteristics of the comorbidity of pain and depression and tested the effect of fluoxetine (FLX) on these measures. Objective: The current study examined whether an LDH model showed the behavioral and biochemical alterations that were in accordance with the characteristics of the comorbidity of pain and depression and tested the effect of FLX on these measures. Methods: The LDH animal model was generated by the implantation of the autologous nucleus pulposus on the left L5 nerve root just proximal to the dorsal root ganglion in Wistar rats. Pain intensity was evaluated by mechanical allodynia and thermal hyperalgesia, and changes in depressive behavior were examined by the taste preference and forced swim tests. Hippocampal serotonin (5-HT) levels were measured by liquid chromatography-mass spectrometry, and tumor necrosis factor-α (TNF-α) mRNA was quantified using real-time reverse transcriptase PCR. Results: LDH resulted in chronic pain, which further induced depressive behavior that persisted for 6 weeks after surgery. There were decreased 5-HT concentrations and upregulated TNF-α mRNA levels that were accompanied by behavioral changes. FLX treatment improved depressive behavior and moderately alleviated pain through increased 5-HT concentrations, and inhibited TNF-α mRNA expression. Conclusions: In summary, our studies provide initial evidence that the LDH chronic pain model might serve as a model of the comorbidity of low back pain and depression. The finding that FLX improved depressive behavior and pain through normalized 5-HT concentrations and TNF-α mRNA expression establishes the initial mechanism of the comorbidity of pain and depression.

In breast milk, 2'-Fucosyllactose (2'FL) is the most abundant breast milk oligosaccharide and can selectively promote the proliferation of bifidobacteria. This study aimed to explore the effect of ifidobacterial with different utilization capacities of 2'FL on the intestinal microecology of mice. Furthermore, the effects of ifidobacterial with different 2'FL utilization capabilities on mice gut microbiota under the competitive pressure of 2'FL as a carbon source were explored. Compared with the control group, 2'FL, Bifidobacterium (B.) bifidum M130R01M51 + 2'FL, B. longum subsp. Longum CCFM752, and CCFM752 + 2'FL treatments significantly decreased the food intake. Moreover, the water intake, body weight, and fecal water content in all groups showed no significant difference compared with the control group. The combination of B. longum subsp. longum CCFM752 and 2'FL can significantly increase the levels of pro-inflammatory and anti-inflammatory factors. B. bifidum M130R01M51 and mixed strains combined with 2'FL significantly increased the contents of acetic acid and isobutyric acid. The results showed that B. bifidum M130R01M51, B. breve FHuNCS6M1, B. longum subsp. longum CCFM752, and B. longum subsp. infantis SDZC2M4 combined with 2'FL significantly increased the species richness of the gut microbiota. Moreover, B. longum subsp. longum CCFM752 and B. longum subsp. infantis SDZC2M4 significantly increased the abundance of Faecalibaculum and Bifidobacterium, respectively. In conclusion, exploring the impact on intestinal microecology can provide theoretical guidance for the development of personalized prebiotics for different bifidobacteria, which has the potential to improve the ecological imbalance of infant gut microbiota.

The association between diet and inflammatory bowel disease (IBD) has been confirmed. However, the role of protein consumption in IBD remains controversial. This research aimed to explore the effects of milk-based protein (MBP), potato protein (PP), and mixed protein (MP) on the recovery of mice with dextran sulfate sodium (DSS)-induced ulcerative colitis (UC). MP alleviated UC symptoms through reducing colon shortening and tissue damage, decreasing neutrophil infiltration, maintaining the mucous layer integrity, and suppressing the expression of TNF-α, IL-17A, IL-6, and IL-1β. MBP and PP decreased the colon shortening and IL-1β levels but PP increased the MUC2 expression. Additionally, the gut microbial structure and composition were altered after different proteins supplement. Compared to DSS-treated mice, MP-treated mice showed that increased abundances in Coprococcus and Bifidobacterium and decreased abundances in Sutterella, Lactobacillus, and Akkermansia. MBP increased the proportion of Bifidobacterium and reduced Sutterella, but PP increased Ruminococcus and Bifidobacterium and decreased Adlercreutzia. Correspondence analysis of gut microbial composition to determine the effects of protein diets on immune response and pathological characteristics also verified the interaction between gut microbiota and alleviation of colitis. These results provide a theoretical basis for the selection of raw materials for clinical enteral nutrition preparations and potential use for potato protein wastes.

Fructooligosaccharides (FOS) are considered prebiotics and have been proven to selectively promote the growth of Bifidobacterium in the gut. This study aimed to clarify the effects of FOS intake on the composition of luminal and mucosal microbiota in mice. Briefly, mice were fed a 0% or 25% FOS (w/w)-supplemented diet for four weeks, and the composition of luminal and mucosal microbiota, especially the Bifidobacterium, was analyzed by sequencing the V3-V4 region of 16S rRNA and groEL gene, respectively. After FOS intervention, there were significant increases in the total and wall weights of the cecum and the amount of total short-chain fatty acids (SCFAs) in the cecal contents of the mice. At the phylum level, the results showed a significant increase in the relative abundance of Actinobacteria in the contents and mucosa from the cecum to the distal colon in the FOS group. Besides Bifidobacterium, a significant increase was observed in the relative abundance of Coprococcus in all samples at the genus level, which may be partially related to the increase in butyric acid levels in the luminal contents. Furthermore, groEL sequencing revealed that Bifidobacterium pseudolongum was almost the sole bifidobacterial species in the luminal contents (>98%) and mucosa (>89%). These results indicated that FOS can selectively promote B. pseudolongum proliferation in the intestine, either in the lumen or the mucosa from the cecum to the distal colon. Further studies are required to reveal the competitive advantage of B. pseudolongum over other FOS-metabolizing bacteria and the response mechanisms of B. pseudolongum to FOS.

Gut microbiome plays an essential role in asthma development, and probiotic-based manipulation of the gut microbiome has been proposed to prevent asthma. Although the preventive effect of Lactobacillus supplementation against allergies has been reported, the precise Lactobacillus species beneficial for effective prevention of asthma remain unidentified and the underlying mechanisms remain unclear. Therefore, we aimed to investigate the efficacy of oral administration of six Lactobacillus species and the mechanism underlying asthma prevention via gut microbiome modulation. We investigated the effects of oral administration of L. rhamnosus, L. fermentum, L. casei, L. gasseri, L. salivarius, and L. reuteri (five strains of each species) on asthma and gut microbiome of house dust mite (HDM)-treated murine models of asthma. Of these, L. reuteri administration was the most effective: it alleviated airway inflammation, decreased total IgE and HDM-IgG1, and reduced Th2-associated pro-inflammatory cytokines. Moreover, modulation of specific microbial genera by L. reuteri was more effective in asthma prevention than the modulation of the overall microbiota composition. Lactobacillus and Enterococcus were enriched after L. reuteri supplementation and were closely associated with total IgE and IL-13 production. Furthermore, L. reuteri specifically altered the gut microbial function toward butyrate generation. Thus, L. reuteri may reduce the risk of asthma development by modulating specific gut microbiota to improve the lung immune environment. Our study suggests a novel option for gut microbiome manipulation via L. reuteri supplementation for suppression of asthma and other allergic diseases.

Increasing researches have confirmed the relationship between slow-transit constipation and gut microbiota dysbiosis. Many population and animal experiments have identified probiotics as effectors for the relief of constipation symptoms, but the specific mechanism remains unclear. In this intervention study, Lactobacillus rhamnosus strains isolated from five different sources were administered to mice with loperamide-induced constipation, and the impacts of these strains on constipation-related indicators were evaluated. All five strains of L. rhamnosus were found to improve constipation to various degrees. However, contrary to previous studies, the abilities of L. rhamnosus strains to improve constipation symptoms were not associated with the levels of short-chain fatty acids (SCFAs) in the colon. The effects of different strains of L. rhamnosus on constipation relief were associated with different aspects of the GI tract, including gastrointestinal regulatory peptides, neurotransmitters, neurotrophic factors, and gut microbiota. The findings of this study demonstrate that L. rhamnosus strains can alleviate constipation-related symptoms via different pathways independent of SCFAs regulation. This study yields a new perspective for clinical use of probiotics to better improve constipation symptoms, by combining strains with different mechanisms for alleviation of constipation.

Lactobacillus casei, one of the most widely used probiotics, has been reported to alleviate multiple diseases. However, the effects of this species on intestinal diseases are strain-specific. Here, we aimed to screen L. casei strains with inflammatory bowel disease (IBD)-alleviating effects based on in vitro physiological characteristics. Therefore, the physiological characteristics of 29 L. casei strains were determined, including gastrointestinal transit tolerance, oligosaccharide fermentation, HT-29 cell adhesion, generation time, exopolysaccharide production, acetic acid production, and conjugated linoleic acid synthesis. The effects of five candidate strains on mice with induced colitis were also evaluated. The results showed that among all tested L. casei strains, only Lactobacillus casei M2S01 effectively relieved colitis. This strain recovered body weight, restored disease activity index score, and promoted anti-inflammatory cytokine expression. Gut microbiota sequencing showed that L. casei M2S01 restored a healthy gut microbiome composition. The western blotting showed that the alleviating effects of L. casei M2S01 on IBD were related to the inhibition of the NF-κB pathway. A good gastrointestinal tolerance ability may be one of the prerequisites for the IBDalleviating effects of L. casei. Our results verified the efficacy of L. casei in alleviating IBD and lay the foundation for the rapid screening of L. casei strain with IBD-alleviating effects.

Animal development is complex yet surprisingly robust. Animals may develop alternative phenotypes conditional on environmental changes. Under unfavorable conditions, Caenorhabditis elegans larvae enter the dauer stage, a developmentally arrested, long-lived, and stress-resistant state. Dauer larvae of free-living nematodes and infective larvae of parasitic nematodes share many traits including a conserved endocrine signaling module (DA/DAF-12), which is essential for the formation of dauer and infective larvae. We speculated that conserved post-transcriptional regulatory mechanism might also be involved in executing the dauer and infective larvae fate. We used an unbiased sequencing strategy to characterize the microRNA (miRNA) gene complement in C. elegans, Pristionchus pacificus, and Strongyloides ratti. Our study raised the number of described miRNA genes to 257 for C. elegans, tripled the known gene set for P. pacificus to 362 miRNAs, and is the first to describe miRNAs in a Strongyloides parasite. Moreover, we found a limited core set of 24 conserved miRNA families in all three species. Interestingly, our estimated expression fold changes between dauer versus nondauer stages and infective larvae versus free-living stages reveal that despite the speed of miRNA gene set evolution in nematodes, homologous gene families with conserved "dauer-infective" expression signatures are present. These findings suggest that common post-transcriptional regulatory mechanisms are at work and that the same miRNA families play important roles in developmental arrest and long-term survival in free-living and parasitic nematodes.

Rationale: Although sepsis-associated encephalopathy (SAE) is a common psychiatric complication in septic patients, the underlying mechanisms remain unclear. Here, we explored the role of the hippocampus (HPC) - medial prefrontal cortex (mPFC) pathway in cognitive dysfunction in lipopolysaccharide-induced brain injury. Methods: Lipopolysaccharide (LPS, 5 mg/kg, intraperitoneal) was used to induce an animal model of SAE. We first identified neural projections from the HPC to the mPFC via a retrograde tracer and virus expression. The activation viruses (pAAV-CaMKIIα-hM3Dq-mCherry) were injected to assess the effects of specific activation of mPFC excitatory neurons on cognitive tasks and anxiety-related behaviors in the presence of clozapine-N-oxide (CNO). Activation of the HPC-mPFC pathway was evaluated via immunofluorescence staining of c-Fos-positive neurons in mPFC. Western blotting was performed to determine protein levels of synapse- associated factors. Results: We successfully identified a structural HPC-mPFC connection in C57BL/6 mice. LPS-induced sepsis induces cognitive impairment and anxiety-like behaviors. Chemogenetic activation of the HPC-mPFC pathway improved LPS-induced cognitive dysfunction but not anxiety-like behavior. Inhibition of glutamate receptors abolished the effects of HPC-mPFC activation and blocked activation of the HPC-mPFC pathway. The glutamate receptor-mediated CaMKII/CREB/BDNF/TrKB signaling pathway influenced the role of the HPC-mPFC pathway in sepsis-induced cognitive dysfunction. Conclusions: HPC-mPFC pathway plays an important role in cognitive dysfunction in lipopolysaccharide-induced brain injury. Specifically, the glutamate receptor-mediated downstream signaling appears to be an important molecular mechanism linking the HPC-mPFC pathway with cognitive dysfunction in SAE.

Gut microbial disturbance affects allergic diseases including asthma, atopic dermatitis (AD) via the aberrant immune response. Some Bifidobacterial species and strains have been reported to improve AD via modulating immune-microbe interactions in patients. However, the effective metabolites and mechanism of alleviating AD in bifidobacteria remain to be elucidated. This study aimed to explore the microbial metabolite and mechanism of Bifidobacterium longum to improve AD. Based on shotgun metagenomic sequencing and UHPLC Q-Exactive-MS targeted metabolic experiments in vitro and in vivo, we focused on tryptophan metabolism and indole derivatives, which are endogenous ligands for aryl hydrocarbon receptor (AHR). Indole-3-carbaldehyde (I3C), a tryptophan metabolite of B. longum CCFM1029 activated AHR-mediated immune signaling pathway to improve AD symptoms in animal and clinical experiments. B. longum CCFM1029 upregulated tryptophan metabolism and increased I3C to suppress aberrant T helper 2 type immune responses, but these benefits were eliminated by AHR antagonist CH223191. Furthermore, B. longum CCFM1029 reshaped gut microbial composition in AD patients, increased fecal and serum I3C, and maintained the abundance of Lachnospiraceae related to tryptophan metabolism of gut microbiota. The results suggested that based on the interactions of the gut-skin axis, B. longum CCFM1029 upregulated tryptophan metabolism and produced I3C to activate AHR-mediated immune response, alleviating AD symptoms. Indole derivates, microbial metabolites of tryptophan, may be the potential metabolites of bifidobacteria to alleviate AD via the AHR signaling pathway.

Polyethylene glycol (PEG) is one of the most commonly used bowel cleansing methods. Although the safety of PEG for bowel cleansing has been proven, its impact on intestinal microbiota has not been clearly explained, especially in terms of the dynamic changes in intestinal microbiota after PEG bowel cleansing, and there are no consistent results. In this study, stool samples were collected from 12 participants at six time points before and after bowel cleansing. We obtained data on the microbiota of these samples using 16S rRNA gene sequencing and analysis. The data revealed that the structure and composition of the microbiota changed greatly approximately 7 d after intestinal cleansing. The analysis of the dynamic changes in the microbiota showed that the change was most significant at day 3, but the internal structure of the microbiota was similar to that before bowel cleansing. A comparison of the most significantly changed microbiota at different time points before and after bowel cleansing revealed four bacteria: Bacteroides, Roseburia, Eubacterium, and Bifidobacterium. We also established a humanized mouse model to simulate human bowel cleansing using PEG. The results showed that the mouse model achieved similar effects to human bowel cleansing, but its recovery speed was one stage earlier than that of humans. These findings suggest that the intestinal microbiota after bowel cleansing initially underwent a short-term change and then actively returned to its initial status. The results on key bacteria and establishment of mouse models can provide a reference for subsequent research on bowel cleansing.

The aim of this study was to establish continuous therapeutic-dose ampicillin (CTDA)-induced dysbiosis in a mouse model, mimicking typical adult exposure, with a view to using this to assess its impact on gut microbiota, intestinal metabolites and host immune responses. Mice were exposed to ampicillin for 14 days and antibiotic-induced dysbiosis was evaluated by alteration of microbiota and gut permeability. The cecal index was increased in the CTDA group, and the gut permeability indicated by fluorescent dextran, endotoxin and D-Lactate in the serum was significantly increased after antibiotic use. The tight-junction proteins ZO-1 and occludin in the colon were reduced to half the control level in CTDA. We found that alpha-diversity was significantly decreased in mice receiving CTDA, and microbial community structure was altered compared with the control. Key taxa were identified as CTDA-specific, and the relative abundance of Enterococcus and Klebsiella was particularly enriched while Lachnospiraceae, Coprobacillus and Dorea were depleted after antibiotic treatment. In particular, a significant increase in succinate and a reduction in butyrate was detected in CTDA mice, and the triggering of NF-κB enhancement reflected that the host immune response was influenced by ampicillin use. The observed perturbation of the microbiota was accompanied by modulation of inflammatory state; this included increase in interferon-γ and RegIIIγ, and a decrease in secretory IgA in the colon mucosa. This study allowed us to identify the key taxa associated with an ampicillin-induced state of dysbiosis in mice and to characterize the microbial communities via molecular profiling. Thus, this work describes the bacterial ecology of antibiotic exposure model in combination with host physiological characteristics at a detailed level of microbial taxa.

The gut microbiota and microRNAs play important roles in the defense against infection. However, the role of miR-146a in L. monocytogenes infection and gut microbiota remains unclear. We tried to determine whether miR-146a controlled L. monocytogenes infection by regulating the gut microbiota. Wild-type and miR-146a-deficient mice or macrophages were used to characterize the impact of miR-146a on animal survival, cell death, bacterial clearance, and gut microbiota following L. monocytogenes challenge. We found that L. monocytogenes infection induced miR-146a expression both in vitro and in vivo. When compared to wild-type mice, miR-146a-deficient mice were more resistant to L. monocytogenes infection. MiR-146a deficiency in macrophages resulted in reduced invasion and intracellular survival of L. monocytogenes. High-throughput sequencing of 16S rRNA revealed that the gut microbiota composition differed between miR-146a-deficient and wild-type mice. Relative to wild-type mice, miR-146a-deficient mice had decreased levels of the Proteobacteria phylum, Prevotellaceae family, and Parasutterella genus, and significantly increased short-chain fatty acid producing bacteria, including the genera Alistipes, Blautia, Coprococcus_1, and Ruminococcus_1. Wild-type mice co-housed with miR-146a-deficient mice had increased resistance to L. monocytogenes, indicating that miR-146a deficiency guides the gut microbiota to alleviate infection. Together, these results suggest that miR-146a deficiency protects against L. monocytogenes infection by regulating the gut microbiota.

Gut microbiota play important roles in host metabolism, especially in diabetes. However, why different diets lead to similar diabetic states despite being associated with different microbiota is not clear. Mice were fed two high-energy diets (HED) with the same energy density but different fat-to-sugar ratios to determine the associations between the microbiota and early-stage metabolic syndrome. The two diets resulted in different microbiota but similar diabetic states. Interestingly, the microbial gene profiles were not significantly different, and many common metabolites were identified, including l-aspartic acid, cholestan-3-ol (5β, 3α), and campesterol, which have been associated with lipogenesis and inflammation. Our study suggests that different metabolic-syndrome-inducing diets may result in different microbiota but similar microbiomes and metabolomes. This suggests that the metagenome and metabolome are crucial for the prognosis and pathogenesis of obesity and metabolic syndrome.IMPORTANCE Various types of diet can lead to type 2 diabetes. The gut microbiota in type 2 diabetic patients are also different. So, two questions arise: whether there are any commonalities between gut microbiota induced by different pro-obese diets and whether these commonalities lead to disease. Here we found that high-energy diets with two different fat-to-sugar ratios can both cause obesity and prediabetes but enrich different gut microbiota. Still, these different gut microbiota have similar genetic and metabolite compositions. The microbial metabolites in common between the diets modulate lipid accumulation and macrophage inflammation in vivo and in vitro This work suggests that studies that only use 16S rRNA amplicon sequencing to determine how the microbes respond to diet and associate with diabetic state are missing vital information.

The current dogma in ophthalmology and vision research presumes the intraocular environment to be sterile. However, recent evidence of intestinal bacterial translocation into the bloodstream and many other internal organs including the eyes, found in healthy and diseased animal models, suggests that the intraocular cavity may also be inhabited by a microbial community. Here, we tested intraocular samples from over 1000 human eyes. Using quantitative PCR, negative staining transmission electron microscopy, direct culture, and high-throughput sequencing technologies, we demonstrated the presence of intraocular bacteria. The possibility that the microbiome from these low-biomass communities could be a contamination from other tissues and reagents was carefully evaluated and excluded. We also provide preliminary evidence that a disease-specific microbial signature characterized the intraocular environment of patients with age-related macular degeneration and glaucoma, suggesting that either spontaneous or pathogenic bacterial translocation may be associated with these common sight-threatening conditions. Furthermore, we revealed the presence of an intraocular microbiome in normal eyes from non-human mammals and demonstrated that this varied across species (rat, rabbit, pig, and macaque) and was established after birth. These findings represent the first-ever evidence of intraocular microbiota in humans.