Intestinal Microbial Dysbiosis Research Articles

Morphine mediated neutrophil infiltration in intestinal tissue play essential role in histological damage and microbial dysbiosis

ABSTRACT The gut microbial ecosystem exhibits a complex bidirectional communication with the host and is one of the key contributing factors in determining mucosal immune homeostasis or an inflammatory state. Opioid use has been established to induce gut microbial dysbiosis consistent with increased intestinal tissue inflammation. In this study, we investigated the role of infiltrated immune cells in morphine-induced intestinal tissue damage and gut microbial dysbiosis in mice. Results reveal a significant increase in chemokine expression in intestinal tissues followed by increased neutrophil infiltration post morphine treatment which is direct consequence of a dysbiotic microbiome since the effect is attenuated in antibiotics treated animals and in germ-free mice. Neutrophil neutralization using anti-Ly6G monoclonal antibody showed a significant decrease in tissue damage and an increase in tight junction protein organization. 16S rRNA sequencing on intestinal samples highlighted the role of infiltrated neutrophils in modulating microbial community structure by providing a growth benefit for pathogenic bacteria, such as Enterococcus, and simultaneously causing a significant depletion of commensal bacteria, such as Lactobacillus. Taken together, we provide the first direct evidence that neutrophil infiltration contributes to morphine-induced intestinal tissue damage and gut microbial dysbiosis. Our findings implicate that inhibition of neutrophil infiltration may provide therapeutic benefits against gastrointestinal dysfunctions associated with opioid use.

Role of Intestinal Microbes in Chronic Liver Diseases.

With the recent availability and upgrading of many emerging intestinal microbes sequencing technologies, our research on intestinal microbes is changing rapidly. A variety of investigations have found that intestinal microbes are essential for immune system regulation and energy metabolism homeostasis, which impacts many critical organs. The liver is the first organ to be traversed by the intestinal portal vein, and there is a strong bidirectional link between the liver and intestine. Many intestinal factors, such as intestinal microbes, bacterial composition, and intestinal bacterial metabolites, are deeply involved in liver homeostasis. Intestinal microbial dysbiosis and increased intestinal permeability are associated with the pathogenesis of many chronic liver diseases, such as alcoholic fatty liver disease (AFLD), non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), chronic hepatitis B (CHB), chronic hepatitis C (CHC), autoimmune liver disease (AIH) and the development of hepatocellular carcinoma (HCC). Intestinal permeability and dysbacteriosis often lead to Lipopolysaccharide (LPS) and metabolites entering in serum. Then, Toll-like receptors activation in the liver induces the exposure of the intestine and liver to many small molecules with pro-inflammatory properties. And all of these eventually result in various liver diseases. In this paper, we have discussed the current evidence on the role of various intestinal microbes in different chronic liver diseases. As well as potential new therapeutic approaches are proposed in this review, such as antibiotics, probiotics, and prebiotics, which may have an improvement in liver diseases.

Effects of the Gut Microbiota and Barrier Function on Melatonin Efficacy in Alleviating Liver Injury.

Environmental cadmium (Cd) exposure has been associated with severe liver injury. In contrast, melatonin (Mel) is a candidate drug therapy for Cd-induced liver injury due to its diverse hepatoprotective activities. However, the precise molecular mechanism by which Mel alleviates the Cd-induced liver injury, as well as the Mel–gut microbiota interaction in liver health, remains unknown. In this study, mice were given oral gavage CdCl2 and Mel for 10 weeks before the collection of liver tissues and colonic contents. The role of the gut microbiota in Mel’s efficacy in alleviating the Cd-induced liver injury was evaluated by the gut microbiota depletion technique in the presence of antibiotic treatment and gut microbiota transplantation (GMT). Our results revealed that the oral administration of Mel supplementation mitigated liver inflammation, endoplasmic reticulum (ER) stress and mitophagy, improved the oxidation of fatty acids, and counteracted intestinal microbial dysbiosis in mice suffering from liver injury. It was interesting to find that neither Mel nor Cd administration induced any changes in the liver of antibiotic-treated mice. By adopting the GMT approach where gut microbiota collected from mice in the control (CON), Cd, or Mel + Cd treatment groups was colonized in mice, it was found that gut microbiota was involved in Cd-induced liver injury. Therefore, the gut microbiota is involved in the Mel-mediated mitigation of ER stress, liver inflammation and mitophagy, and the improved oxidation of fatty acids in mice suffering from Cd-induced liver injury.

The COVID-19 Pandemic and Post-Infection Irritable Bowel Syndrome: What Lies Ahead for Gastroenterologists

The COVID-19 Pandemic and Post-Infection Irritable Bowel Syndrome: What Lies Ahead for Gastroenterologists

Intestinal changes associated with nitrite exposure in Bufo gargarizans larvae: Histological damage, immune response, and microbiota dysbiosis.

Nitrite is a ubiquitous toxic compound in aquatic ecosystems and has negative effects on aquatic organisms. The intestine and the trillions of microbes that inhabit it, play an integral role in maintaining digestive and immune functions. However, the effects of nitrite on intestinal health and microflora have been poorly investigated. Therefore, the present study evaluated the response of intestinal histology, immunity, digestive enzyme activities and microbiota to nitrite exposure in Bufo gargarizans tadpoles. The results showed that nitrite caused damage to the intestine and impaired digestive performance. Significant changes in the transcriptional profiles of genes involved in oxidative stress (sod, gpx and hsp), inflammation, and immunity (socs3, il-27, il-1β and il-17d) were observed in the NO2-N treatment groups. In addition, exposure to nitrite induced alterations of intestinal microbial diversity, structure and composition, suggesting that nitrite may lead to intestinal microbiota dysbiosis. It is noteworthy that probiotics (e.g., Bacteroidetes and Fusobacteria) were decreased after exposure to nitrite, whereas potentially opportunistic pathogens such as Proteobacteria and Enterobacteriaceae were elevated. Functional prediction and correlation analysis suggested that the above changes may interfere with metabolic function and trigger various diseases. Taken together, we concluded that nitrite exposure induced intestinal microbial dysbiosis, which may lead to immune dysfunction and metabolic disorder, and ultimately to histological damages in B. gargarizans. Further, this study will provide a scientific basis for further understanding the risk of nitrite pollution on the intestinal health of amphibians.

Correlations between Intestinal Microbiota and Clinical Characteristics in Colorectal Adenoma/Carcinoma.

Background Most of colorectal cancer (CRC) cases are sporadic and develop along the adenoma-carcinoma sequence. Intestinal microbial dysbiosis is involved in the development of colorectal cancer. However, there are still no absolute markers predicting the progression from adenoma to carcinoma. Aims To investigate the characteristics of intestinal microbiota in colorectal adenoma and carcinoma patients and the correlations with clinical characteristics. Methods Fecal samples were collected from 154 colorectal carcinoma patients (CRC group), 20 colorectal adenoma patients (AD group), and 199 healthy controls (control group). The intestinal microbiota was investigated by 16S rRNA gene sequencing. Results Compared to the healthy controls, microbial diversity was dramatically decreased in AD/CRC. At the genus level, Acidaminococcus significantly decreased with the order of control-AD-CRC (P < 0.05). Parvimonas, Peptostreptococcus, Prevotella, Butyricimonas, Alistipes, and Odoribacter were the key genera in the network of colorectal adenoma/carcinoma-associated bacteria. Combination of the top 10 most important species, including Butyricimonas synergistica, Agrobacterium larrymoorei, Bacteroides plebeius, Lachnospiraceae bacterium feline oral taxon 001, Clostridium scindens, Prevotella heparinolytica, bacterium LD2013, Streptococcus mutans, Lachnospiraceae bacterium 19gly4, and Eubacterium hallii, showed the best performance in distinguishing AD patients from CRC (AUC = 85.54%, 95% CI: 78.83%-92.25%). The clinicopathologic features, including age, sex, tumor location, differentiation degree, and TNM stage, were identified to be closely linked to the intestinal microbiome in CRC. Conclusion Several intestinal bacteria changed along the adenoma-carcinoma sequence and might be the potential markers for the diagnosis and treatment of colorectal adenoma/carcinoma. Intestinal microbiota characteristics in CRC should account for the host factors.

Intestinal Microbiota in Colorectal Adenoma-Carcinoma Sequence.

BackgroundMost colorectal cancer (CRC) cases are sporadic and develop along the adenoma-carcinoma sequence. Intestinal microbial dysbiosis is involved in the development of colorectal cancer. However, there are still no absolute markers predicting the progression from adenoma to carcinoma. This study aimed to investigate the characteristics of intestinal microbiota in patients with colorectal adenoma and carcinoma and its correlations with clinical characteristics.MethodsFecal samples were collected from 154 patients with CRC, 20 patients with colorectal adenoma (AD) and 199 healthy controls. To analyze the differences in the intestinal microbiota, 16S rRNA gene sequencing was conducted.ResultsAt the genus level, there were four significantly different genera among the three groups, namely Acidaminococcus, Alloprevotella, Mycoplasma, and Sphingobacterium, while Acidaminococcus significantly decreased with the order of Control-AD-CRC (P < 0.05). In addition, Parvimonas, Peptostreptococcus, Prevotella, Butyricimonas, Alistipes, and Odoribacter were the key genera in the network of colorectal adenoma/carcinoma-associated bacteria. The top 10 most important species, including Butyricimonas synergistica, Agrobacterium larrymoorei, Bacteroides plebeius, Lachnospiraceae bacterium feline oral taxon 001, Clostridium scindens, Prevotella heparinolytica, bacterium LD2013, Streptococcus mutans, Lachnospiraceae bacterium 19gly4, and Eubacterium hallii, showed the best performance in distinguishing AD from CRC (AUC = 85.54%, 95% CI: 78.83–92.25%). The clinicopathologic features, including age, gender, tumor location, differentiation degree, and TNM stage, were identified to be closely linked to the intestinal microbiome in CRC.ConclusionSeveral intestinal bacteria changed along the adenoma-carcinoma sequence and might be the potential markers for the diagnosis and treatment of colorectal adenoma/carcinoma. Intestinal microbiota characteristics in CRC should account for the host factors.

Absence of Bacteria Permits Fungal Gut-To-Brain Translocation and Invasion in Germfree Mice but Ageing Alone Does Not Drive Pathobiont Expansion in Conventionally Raised Mice.

Age-associated changes in the structure of the intestinal microbiome and in its interaction with the brain via the gut-brain axis are increasingly being implicated in neurological and neurodegenerative diseases. Intestinal microbial dysbiosis and translocation of microbes and microbial products including fungal species into the brain have been implicated in the development of dementias such as Alzheimer’s disease. Using germ-free mice, we investigated if the fungal gut commensal, Candida albicans, an opportunistic pathogen in humans, can traverse the gastrointestinal barrier and disseminate to brain tissue and whether ageing impacts on the gut mycobiome as a pre-disposing factor in fungal brain infection. C. albicans was detected in different regions of the brain of colonised germ-free mice in both yeast and hyphal cell forms, often in close association with activated (Iba-1+) microglial cells. Using high-throughput ITS1 amplicon sequencing to characterise the faecal gut fungal composition of aged and young SPF mice, we identified several putative gut commensal fungal species with pathobiont potential although their abundance was not significantly different between young and aged mice. Collectively, these results suggest that although some fungal species can travel from the gut to brain where they can induce an inflammatory response, ageing alone is not correlated with significant changes in gut mycobiota composition which could predispose to these events. These results are consistent with a scenario in which significant disruptions to the gut microbiota or intestinal barrier, beyond those which occur with natural ageing, are required to allow fungal escape and brain infection.

Sanguinarine ameliorates DSS induced ulcerative colitis by inhibiting NLRP3 inflammasome activation and modulating intestinal microbiota in C57BL/6 mice

BackgroundSanguinarine (SAN) is an important natural anti-inflammatory constitutes and dietary supplementation with SAN could improve the relative length of the intestine, alter gut microbiota, and enhance growth performance of pigs, broiler chickens, and cattle. However, it is unclear whether it has the therapeutic effect on ulcerative colitis (UC). PurposeThis study aimed to investigate the therapeutic effect of SAN on UC and explore its mechanisms of action. Study design and methodsSeveral efficacy indexes of SAN on dextran sulfate sodium (DSS)-induced C57BL/6 mice were evaluated. ELISA kit and western blot analysis were used to evaluate it's anti-inflammatory effect and the mechanism of action. 16S rDNA sequencing detection was used to determine the impact of SAN on gut microbiota. ResultsSAN and Sulfasalazine could significantly improve the colon length, the weight loss, the symptoms and the pathological injury of colon in DSS-induced mice. Meanwhile, SAN could decrease the levels of pro-inflammatory cytokines (TNF-α, IFN-γ, IL-1β, IL-6, IL-13 and IL-18) and increase the levels of anti-inflammatory cytokines (IL-4 and IL-10) in colon, and suppress DSS-induced high expressions of NLRP3, caspase-1 and IL-1β. In addition, SAN (0.5, 1 μM) could inhibit the expression level of NLRP3 and the activation of caspase-1 and IL-1β in lipopolysaccharide-stimulated THP-1 cells in non-cytotoxic doses, which was similar to that of MCC950, a specific inhibitor of NLRP3 inflammasome activation. The abundance changes of many genera such as Muribaculaceae_unclassified, Escherichia-Shigella, Lachnospiraceae_NK4A136_group and Helicobacter were also closely related to the improvement of SAN on intestinal inflammatory response. ConclusionSAN exhibited therapeutic effect on DSS-induced colitis by blocking NLRP3-(Caspase-1)/IL-1β pathway and improving intestinal microbial dysbiosis. SAN might be developed to treat UC and other disorders associated with microbial dysbiosis.

Octanoate Alleviates Dietary Soybean Oil-Induced Intestinal Physical Barrier Damage, Oxidative Stress, Inflammatory Response and Microbial Dysbiosis in Large Yellow Croaker (Larimichthys Crocea).

Octanoate is a type of classical medium-chain fatty acids, which is widely used to treat neurological and metabolic syndrome. However, the specific role of octanoate in repairing intestinal health impairment is currently unknown. Therefore, we investigated whether dietary octanoate repaired the intestinal damage induced by surplus soybean oil in Larimichthys crocea. In this study, dietary octanoate alleviated abnormal morphology of the intestine and enhanced expression of ZO-1 and ZO-2 to improve intestinal physical barrier. Further, dietary octanoate increased antioxidant enzymic activities and decreased the level of ROS to alleviate the intestinal oxidative stress. Dietary octanoate also attenuated the expression of proinflammatory cytokines and the polarity of macrophage to reduce the intestinal inflammatory response. Moreover, the result of intestinal microbial 16S rRNA sequence showed that dietary octanoate repaired the intestinal mucosal microbial dysbiosis, and increased the relative abundance of Lactobacillus. Dietary octanoate supplementation also increased the level of acetic acid in intestinal content and serum through increasing the abundance of acetate-producing strains. Overall, in Larimichthys crocea, dietary octanoate might alleviated oxidative stress, inflammatory response and microbial dysbiosis to repair the intestinal damage induced by surplus soybean oil. This work provides vital insights into the underlying mechanisms and treatment strategies for intestinal damage in vertebrates.

Breath Testing and Small Bowel Organisms in Clinical Practice.

Breath Testing and Small Bowel Organisms in Clinical Practice.

Immunomodulatory activity of a water-soluble polysaccharide extracted from mussel on cyclophosphamide-induced immunosuppressive mice models

This study aimed to investigate the protective effect of mussel polysaccharide (MP) on cyclophosphamide (Cy)-induced intestinal mucosal immunosuppression and microbial dysbiosis in mice. MP was shown to stimulate secretion of cytokines (SIgA, IL-2, IF-γ, IL-4, IL-10) and production of transcription factors (occludin, claudin-1, ZO-1, mucin-2, IL-2, IF-γ, IL-4, IL-10). Key proteins (p-IκB-α, p-p65) of the NF-κB pathway were upregulated after MP administration. SCFAs levels, which were decreased after the Cy treatment, were improved after treatment with MP. Furthermore, 16 S rRNA sequencing data of fecal samples revealed, through α-diversity and β-diversity analysis, that MP improved microbial community diversity and modulate the overall composition of gut microbiota. Taxonomic composition analysis showed that MP increased the abundance of probiotics species (Lactobacillus) and decreased the proportion of pathogenic species (Desulfovibrio). These findings suggested that MP has a potential immunomodulatory activity on the immunosuppressive mice.

Altered immunity to microbiota, B cell activation and depleted γδ/resident memory T cells in colorectal cancer

The role of microbiota:immune system dysregulation in the etiology of colorectal cancer (CRC) is poorly understood. CRC develops in gut epithelium, accompanied by low level inflammatory signaling, intestinal microbial dysbiosis and immune dysfunction. We examined populations of intraepithelial lymphocytes in non-affected colonic mucosa of CRC and healthy donors and circulating immune memory to commensal bacterial species and yeasts. γδ T cells and resident memory T cells, populations with a regulatory CD39-expressing phenotype, were found at lower frequencies in the colonic tissue of CRC donors compared to healthy controls. Patterns of T cell proliferative responses to a panel of commensal bacteria were distinct in CRC, while B cell memory responses to several bacteria/yeast were significantly increased, accompanied by increased proportions of effector memory B cells, transitional B cells and plasmablasts in blood. IgA responses to mucosal microbes were unchanged. Our data describe a novel immune signature with similarities to and differences from that of inflammatory bowel disease. They implicate B cell dysregulation as a potential contributor to parainflammation and identify pathways of weakened barrier function and tumor surveillance in CRC-susceptible individuals.

Altered Mucosal Immune-Microbiota Interactions in Familial Adenomatous Polyposis.

Familial adenomatous polyposis (FAP) is a condition caused by a constitutional pathogenic variant of the adenomatous polyposis coli gene that results in intestinal adenoma formation and colorectal cancer, necessitating pre-emptive colectomy. We sought to examine interaction between the mucosal immune system and commensal bacteria in FAP to test for immune dysfunction that might accelerate tumorigenesis. Colonic biopsies were obtained from macroscopically normal mucosal tissue from 14 healthy donors and 13 patients with FAP during endoscopy or from surgical specimens. Intraepithelial and lamina propria lymphocytes were phenotyped. Intraepithelial microbes were labeled with anti-IgA/IgG and analyzed by flow cytometry. Proportions of resident memory CD103-expressing CD8 + and γδ T-cell receptor + intraepithelial lymphocytes were dramatically reduced in both the left and right colon of patients with FAP compared with healthy controls. In lamina propria, T cells expressed less CD103, and CD4 + CD103 + cells expressed less CD73 ectonucleotidase. IgA coating of epithelia-associated bacteria, IgA + peripheral B cells, and CD4 T-cell memory responses to commensal bacteria were increased in FAP. Loss of resident memory T cells and γδ T cells in mucosal tissue of patients with FAP accompanies intestinal microbial dysbiosis previously reported in this precancerous state and suggests impaired cellular immunity and tumor surveillance. This may lead to barrier dysfunction, possible loss of regulatory T-cell function, and excess IgA antibody secretion. Our data are the first to implicate mucosal immune dysfunction as a contributing factor in this genetically driven disease and identify potentially critical pathways in the etiology of CRC.

Iron-mediated epigenetic activation of NRF2 targets

The toxic effects of excess dietary iron within the colonic lumen are well documented, particularly in the context of Inflammatory Bowel Disease (IBD) and Colorectal Cancer (CRC). Proposed mechanisms that underpin iron-associated intestinal disease include: (1) the pro-inflammatory and ROS-promoting nature of iron, (2) gene-expression alterations, and (3) intestinal microbial dysbiosis. However, to date no studies have examined the effect of iron on the colonic epigenome. Here we demonstrate that chronic iron exposure of colonocytes leads to significant hypomethylation of the epigenome. Bioinformatic analysis highlights a significant epigenetic effect on NRF2 (nuclear factor erythroid 2-related factor 2) pathway targets (including NAD(P)H Quinone Dehydrogenase 1 [NQO1] and Glutathione peroxidase 2 [GPX2]); this demethylating effect was validated and subsequent gene and protein expression quantified. These epigenetic modifications were not observed upon the diminishment of cellular lipid peroxidation with endogenous glutathione and the subsequent removal of iron. Additionally, the induction of TET1 expression was found post-iron treatment, highlighting the possibility of an oxidative-stress induction of TET1 and subsequent hypomethylation of NRF2 targets. In addition, a strong time dependence on the establishment of iron-orchestrated hypomethylation was found which was concurrent with the increase in the intracellular labile iron pool (LIP) and lipid peroxidation levels. These epigenetic changes were further validated in murine intestinal mucosa in models administered a chronic iron diet, providing evidence for the likelihood of dietary-iron mediated epigenetic alterations in vivo. Furthermore, significant correlations were found between NQO1 and GPX2 demethylation and human intestinal tissue iron-status, thus suggesting that these iron-mediated epigenetic modifications are likely in iron-replete enterocytes. Together, these data describe a novel mechanism by which excess dietary iron is able to alter the intestinal phenotype, which could have implications in iron-mediated intestinal disease and the regulation of ferroptosis.

Intestinal microbial dysbiosis induced tau accumulation establishes a gut‐brain correlation for pathology Alzheimer's disease in Drosophila melanogaster

AbstractBackgroundTo analyze the concept of whether enteric dysbiosis contributes to the aggravation of tau protein, Drosophila melanogaster was used as a transgenic model organism. To study how the exposure of Pseudomonas sp., a gram‐negative bacteria, influences tau accumulation and neurodegeneration thereby understanding the gut‐brain correlation for the pathology of Alzheimer’s Disease.MethodThe versatile Gal4‐UAS gene expression system was used to express wild‐type tau with the help of pan‐eye specific GMR‐Gal4 in the flies. All the flies were exposed to Pseudomonas sp. to initiate the gut microbial dysbiosis. The extent of neurodegeneration was quantified by automated analysis of the degenerated region in the eye, the number of aggregates, and immunofluorescence quantification in the medulla. To understand the response of glial cells upon bacterial infection in tauopathy‐related dementia, tau was driven by glia‐specific Repo‐GAL4. Similarly, neuroinflammation which is found in tauopathies was studied using an eye‐specific driver line GMR‐GAL4, UAS‐ eiger/CyO.ResultUpon exposure of Pseudomonas sp. on the wild type tau (tauwt) around the medulla, the degeneration was faster and, there was an increase in the levels of tau as compared to the control. Downregulation of Atg 1 and Atg 18 gene along with significant upregulation of Atg 12 is observed in tau expressing infected flies compared to tau expressing control flies. There was a significant degeneration as well as an increase in the number of aggregates in the medulla of the optic lobe. Similar degeneration was observed in flies expressing tauwt and egr along with an increased accumulation of tau in both retina and medulla.ConclusionWhen the flies expressing tau are subjected to the pathogen, and aggravation in tau accumulation is observed along with neuroinflammation and changes in the homeostasis. Due to its role in maintaining of body’s homeostasis, the gut‐brain correlation can have both detrimental and beneficial effects on the brain and the survival of neurons.

Lactate-utilizing bacteria ameliorates DSS-induced colitis in mice

Inflammatory bowel diseases (IBD) stem from alterations in the intestinal immune system and microbial dysbiosis, but the precise interactions between bacteria and IBD remain obscure. The commensal microbiota have a profound impact on human health and diseases. Here, we developed a selective culture medium for lactate-utilizing bacteria (LUB) that function as candidate probiotics to ameliorate IBD using a mouse model. Firstly, LUB, including Megasphaera, were enriched from human faeces using a selective medium with lactate. LUB efficiently attenuated the pathology of colitis induced by dextran sulphate sodium (DSS). Next, LUB administration counteracted the dysbiosis associated with the intestinal inflammatory process, and elevated the proportion of Escherichia-Shigella in intestines. Moreover, E. coli isolated from healthy faeces downstream recapitulated lactate-utilizing bacterial community to ameliorate the severity of DSS-induced acute colitis. In conclusion, our finding revealed that LUB were sufficient to exert inflammatory protection against colitis in mice, highlighting a novel therapeutic strategy to use LUB as potentially curable probiotics for therapeutic manipulation for IBD.

Microbiome-Mediated Immune Signaling in Inflammatory Bowel Disease and Colorectal Cancer: Support From Meta-omics Data.

Chronic intestinal inflammation and microbial dysbiosis are hallmarks of colorectal cancer (CRC) and inflammatory bowel diseases (IBD), such as Crohn’s disease and ulcerative colitis. However, the mechanistic relationship between gut dysbiosis and disease has not yet been fully characterized. Although the “trigger” of intestinal inflammation remains unknown, a wealth of evidence supports the role of the gut microbiome as a mutualistic pseudo-organ that significantly influences intestinal homeostasis and is capable of regulating host immunity. In recent years, culture-independent methods for assessing microbial communities as a whole (termed meta-omics) have grown beyond taxonomic identification and genome characterization (metagenomics) into new fields of research that collectively expand our knowledge of microbiomes. Metatranscriptomics, metaproteomics, and metabolomics are meta-omics techniques that aim to describe and quantify the functional activity of the gut microbiome. Uncovering microbial metabolic contributions in the context of IBD and CRC using these approaches provides insight into how the metabolic microenvironment of the GI tract shapes microbial community structure and how the microbiome, in turn, influences the surrounding ecosystem. Immunological studies in germ-free and wild-type mice have described several host-microbiome interactions that may play a role in autoinflammation. Chronic colitis is a precursor to CRC, and changes in the gut microbiome may be an important link triggering the neoplastic process in chronic colitis. In this review, we describe several microbiome-mediated mechanisms of host immune signaling, such as short-chain fatty acid (SCFA) and bile acid metabolism, inflammasome activation, and cytokine regulation in the context of IBD and CRC, and discuss the supporting role for these mechanisms by meta-omics data.

Association of Intestinal Microbial Dysbiosis With Chronic Obstructive Pulmonary Disease.

Normal gut flora plays various beneficial roles for the human body, including the protection against inflammatory states and mucosal viral infections. It also influences the immune system of the body. The metabolites produced by the gut bacteria control local and other systemic organs' immune functions like the lungs and brain, playing a role in their response to acute and chronic illnesses. Probiotics have shown beneficial effects on lung health. On the contrary, dysbiosis is associated with several diseases, including asthma, chronic bronchitis, emphysema, allergies, and other acute viral infections. By altering the diet of patients with respiratory diseases like patients with chronic obstructive pulmonary diseases (COPD), we may be able to mitigate their conditions. This literature review aims to discuss the mechanisms altering the gastrointestinal flora, the pathophysiology of gut and lung axis, the role of diet in gut microbe health, and the association of COPD with gut dysbiosis and peptic ulcer disease (PUD). We have extracted the data from PubMed and Google Scholar, consisting of review articles, case-control studies, and animal studies. The studies showed an association between gut microbes and different lung diseases. It is found that gut dysbiosis not only disrupts intestinal immunity but may also facilitate the development of COPD. Present studies also show an increased seroprevalence of Helicobacter pylori in patients with COPD. The strategies that can improve lung functions, especially in COPD patients, include prebiotics and probiotic supplementation to a diet more balanced than the current average American diet.

P16 I NK 4a Deletion Ameliorates Damage of Intestinal Epithelial Barrier and Microbial Dysbiosis in a Stress-Induced Premature Senescence Model of Bmi-1 Deficiency.

This study aimed to determine whether Bmi-1 deficiency leads to intestinal epithelial barrier destruction and microbiota dysfunction, which members of the microbial community alter barrier function with age, and whether p16INK4a deletion could reverse the damage of intestinal epithelial barrier and microbial dysbiosis. Intestines from Bmi-1–deficient (Bmi-1–/–), Bmi-1 and p16INK4a double-knockout (Bmi-1–/–p16INK4a–/–), and wild-type mice were observed for aging and inflammation. Duolink Proximity Ligation Assay, immunoprecipitation, and construction of p16INK4a overexpressed adenovirus and the overexpressed plasmids of full-length, mutant, or truncated fragments for occludin were used for analyzing the interaction between p16INK4a and occludin. High-throughput sequencing of V4 region amplicon of 16S ribosomal RNA was conducted using intestinal microbiota. We found Bmi-1 deficiency destructed barrier structure, barrier function, and tight junction (TJ) in intestinal epithelium; decreased the TJ proteins; increased tumor necrosis factor α (TNF-α)–dependent barrier permeability; and up-regulated proinflammatory level of macrophages induced by intestinal microbial dysbiosis. The transplantation of fecal microbiota from wild-type mice ameliorated TJ in intestinal epithelium of Bmi-1–/– and Bmi-1–/–p16INK4a–/– mice. Harmful bacteria including Desulfovibrio, Helicobacter, and Oscillibacter were at a higher level in Bmi-1–/– mice. More harmful bacteria Desulfovibrio entered the epithelium and promoted macrophages-secreted TNF-α and caused TNF-α–dependent barrier permeability and aging. Accumulated p16INK4a combined with occludin at the 1st–160th residue in cytoplasm of intestinal epithelium cells from Bmi-1–/– mice, which blocked formation of TJ and the repair of intestinal epithelium barrier. P16INK4a deletion could maintain barrier function and microbiota balance in Bmi-1–/– mice through strengthening formation of TJ and decreasing macrophages-secreted TNF-α induced by Desulfovibrio entering the intestinal epithelium. Thus, Bmi-1 maintained intestinal TJ, epithelial barrier function, and microbiota balance through preventing senescence characterized by p16INK4a accumulation. The clearance of p16INK4a-positive cells in aging intestinal epithelium would be a new method for maintaining barrier function and microbiota balance. The residues 1–160 of occludin could be a novel therapeutic target for identifying small molecular antagonistic peptides to prevent the combination of p16INK4a with occludin for protecting TJ.