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Intestinal inflammation creates a different environment for the gut microbes. Hematoxylin and eosin (H&E)-stained colon Swiss roll sections from a 9-month-old wild-type (WT) mouse (left; healthy) and an agematched interleukin-10 knockout (Il-10 −/− ) mouse (right, inflamed). (Left, inset) The WT mouse colon has a wellorganized lining of villi (gray box), with the presence of columnar epithelial cells (with microvilli; blue arrow) and goblet cells (black arrow). (Right, inset) The inflamed Il-10 −/− mouse colon shows loss of the regular villus structures, thickening of the mucosa, crypt elongation (brown arrow), infiltration of inflammatory immune cells (yellow arrow), depletion of goblet cells, disruption of the brush border (red arrow) and loss of surface epithelial cells (green arrow).
Source publication
Microbiome analysis has identified a state of microbial imbalance (dysbiosis) in patients with chronic intestinal inflammation and colorectal cancer. The bacterial phylum Proteobacteria is often overrepresented in these individuals, with Escherichia coli being the most prevalent species. It is clear that a complex interplay between the host, bacter...
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Pioneer microbiota colonizing the newborn gastrointestinal tract has long-lasting effects on host health. Restoration of the gut microbial community, following dysbiosis during the neonatal period, may be one strategy to prevent undesirable health outcomes linked to an altered neonatal gut microbiome. Without appropriate animal models that recreate...
Citations
... 13 Dysbiosis is defined as a loss of beneficial microbial organisms, the expansion of pathobionts or potentially harmful microorganisms, and/or loss of overall microbial diversity. 14,15 While many environmental factors, such as dietary fluctuations and socio-geographical dynamics, are known to cause gut dysbiosis, 16 oral antibiotic administration is perhaps the most well-known perturbator of microbial community structure. As evidenced in the systematic review by Zimmermann and Curtis (2019), studies demonstrating changes in gut microbiome structure and function following antibiotic exposure are numerous. ...
Emerging evidence indicates that antibiotic-induced dysbiosis can play an etiological role in the pathogenesis of neuropsychiatric disorders. However, most of this evidence comes from rodent models. The objective of this study was to evaluate if antibiotic-induced gut dysbiosis can elicit changes in gut metabolites and behavior indicative of gut-brain axis disruption in common marmosets (Callithrix jacchus) – a nonhuman primate model often used to study sociability and stress. We were able to successfully induce dysbiosis in marmosets using a custom antibiotic cocktail (vancomycin, enrofloxacin and neomycin) administered orally for 28 days. This gut dysbiosis altered gut metabolite profiles, behavior, and stress reactivity. Increase in gut Fusobacterium spp. post-antibiotic administration was a novel dysbiotic response and has not been observed in any rodent or human studies to date. There were significant changes in concentrations of several gut metabolites which are either neurotransmitters (e.g., GABA and serotonin) or have been found to be moderators of gut-brain axis communication in rodent models (e.g., short-chain fatty acids and bile acids). There was an increase in affiliative behavior and sociability in antibiotic-administered marmosets, which might be a coping mechanism in response to gut dysbiosis-induced stress. Increase in urinary cortisol levels after multiple stressors provides more definitive proof that this model of dysbiosis may cause disrupted communication between gut and brain in common marmosets. This study is a first attempt to establish common marmosets as a novel model to study the impact of severe gut dysbiosis on gut-brain axis cross-talk and behavior.
... Some researches have agreed that the functional imbalance triggered by certain types of dysbiotic gut microbiota may cause pro-inflammatory responses and epithelial cell transformation that leads to cancer. [26][27][28] As proposed by Yang and Jobin 28 in their 'driver-passenger theory', the predominant clusters of mucosal bacteria (the driver) cause persistent DNA damage in human epithelial tissue, thus triggering tumor formation. The changes in the surrounding microenvironment during the tumorigenesis will then allow the colonization of opportunistic bacteria (the passengers) capable of facilitating tumor progression. ...
... [40][41][42] Increased production of microbial antigens and metabolites due to changes in microbial activity can majorly influence on the immune response and be a source of chronic inflammation. 28,43 Increased production of SCFA, like butyrate, might have a detrimental effect on the intestinal barrier, damaging epithelial cells and their junctions through activation of pro-inflammatory mediators such as cytokines, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6). 44,45 Some bacterial species produce toxins that breach the intestinal epithelial barrier and trigger a mucosal inflammatory response. ...
Recent metagenomic evidence broadly supports the association and causality of gut dysbiosis with the development of colorectal cancer (CRC). Probiotics and prebiotics have been proposed as new preventive and therapeutic adjuncts for CRC management. While promoting the growth of ingested probiotics, an ideal prebiotic fibre should reach the colon intact to be fermented by a distinct group of beneficial commensal bacteria. Therefore, the selection of probiotic bacteria, the growth-promoting prebiotic fibre, and a combination of both probiotics and prebiotics (known
as synbiotics) are critical in preventing carcinogenesis. Despite limited clinically measurable data, findings from preclinical animal studies have recognized the functional role of synbiotics of varying genera, strains, and doses in nourishing beneficial human gut microbiome to evade cancer. Nevertheless, translating such heterogeneous-based data from different study settings and measured outcomes into evidence-based recommendations is a very challenging task. The emerging concept is that an ideal synbiotic combination may effectively modify the intestinal
microflora composition which helps imprint the immune systems for lasting chemoprevention effect. The present article reviews the roles of gut microflora in colorectal carcinogenesis followed by discussing the updated evidence of prebiotic chemoprotective effects in modulating gut microflora and host immunity against CRC. Besides, it also summarized the limitations of the clinical use of probiotics and prebiotics to achieve synergism in formulating ideal synbiotics.
... However, in individuals with inflammatory bowel disease (IBD) and in animal models of gut inflammation, E. coli becomes more dominant in the gut microbiota [24][25][26]. E. coli strains isolated from individuals with IBD often exhibit adherence and invasive properties, displaying virulence characteristics [27]. ...
Background
Formyl peptide receptor 2 (Fpr2) plays a crucial role in colon homeostasis and microbiota balance. Commensal E. coli is known to promote the regeneration of damaged colon epithelial cells. The aim of the study was to investigate the connection between E. coli and Fpr2 in the recovery of colon epithelial cells.
Results
The deficiency of Fpr2 was associated with impaired integrity of the colon mucosa and an imbalance of microbiota, characterized by the enrichment of Proteobacteria in the colon. Two serotypes of E. coli , O22:H8 and O91:H21, were identified in the mouse colon through complete genome sequencing. E. coli O22:H8 was found to be prevalent in the gut of mice and exhibited lower virulence compared to O91:H21. Germ-free (GF) mice that were pre-orally inoculated with E. coli O22:H8 showed reduced susceptibility to chemically induced colitis, increased proliferation of epithelial cells, and improved mouse survival. Following infection with E. coli O22:H8, the expression of Fpr2 in colon epithelial cells was upregulated, and the products derived from E. coli O22:H8 induced migration and proliferation of colon epithelial cells through Fpr2. Fpr2 deficiency increased susceptibility to chemically induced colitis, delayed the repair of damaged colon epithelial cells, and heightened inflammatory responses. Additionally, the population of E. coli was observed to increase in the colons of Fpr2 −/− mice with colitis.
Conclusion
Commensal E. coli O22:H8 stimulated the upregulation of Fpr2 expression in colon epithelial cells, and the products from E. coli induced migration and proliferation of colon epithelial cells through Fpr2. Fpr2 deficiency led to an increased E. coli population in the colon and delayed recovery of damaged colon epithelial cells in mice with colitis. Therefore, Fpr2 is essential for the effects of commensal E. coli on colon epithelial cell recovery.
... Cystic fibrosis results in an increase in pathobiont and pro-inflammatory associated gut bacteria and an overall reduction in bacteria which are linked to anti-inflammatory effects. This shifted microbial composition mirrors aspects of the compositions seen in extremely premature infants [94], inflammatory conditions such as IBD [95], asthma [96] and colorectal cancer (CRC) [97]. An increased relative abundance of bacteria typically associated with the small intestine is frequently found in pwCF, including Lactobacillus, Clostridium, Streptococcus, Veillonella and Enterococcus (e.g.) [48,50,62,64,68,77,78,98,99]. ...
... Cystic fibrosis is associated with increased intestinal inflammation, generating a milieu favouring the growth of pathobiont and pro-inflammatory bacteria, such as E. coli [95]. There does not seem to be a clear relationship between FC and alteration in CF microbiota, although significant inter-subject variation in FC levels have been reported [49,53,71]. ...
Background and Aims
Cystic Fibrosis (CF) is associated with gut dysbiosis, local and systemic inflammation, and impaired immune function. Gut microbiota dysbiosis results from changes in the complex gut milieu in response to CF transmembrane conductance regulator (CFTR) dysfunction, pancreatic malabsorption, diet, medications, and environmental influences. In several diseases, alteration of the gut microbiota influences local and systemic inflammation and disease outcomes. We conducted a systematic review of the gut microbiota in CF and explored factors influencing dysbiosis.
Methods
An electronic search of three databases was conducted in January 2019, and re-run in June 2021. Human, animal, and in vitro studies were included. The primary outcome was differences in the gut microbiota between people with CF (pwCF) and healthy controls. Secondary outcomes included the relationship between the gut microbiota and other factors, including diet, medication, inflammation, and pulmonary function in pwCF.
Results
Thirty-eight studies were identified. The literature confirmed the presence of CF-related gut dysbiosis, characterized by reduced diversity and several taxonomic changes. There was a relative increase of bacteria associated with a pro-inflammatory response coupled with a reduction of those considered anti-inflammatory. However, studies linking gut dysbiosis to systemic and lung inflammation were limited. Causes of gut dysbiosis were multifactorial, and findings were variable. Data on the impact of CFTR modulators on the gut microbiota were limited.
Conclusions
CF-related gut dysbiosis is evident in pwCF. Whether this influences local and systemic disease and is amenable to interventions with diet and drugs, such as CFTR modulators, requires further investigation.
... There is microbial imbalance (dysbiosis) in patients with chronic intestinal inflammation and colorectal cancer. A complex interplay between the host, bacteria, and bacterial genes is implicated in the development of these intestinal diseases [28]. ...
Objective:
Small intestinal bacterial overgrowth (SIBO) syndrome is associated with depression and anxiety. This study aimed to examine for the first time the correlation between personality traits, situational anxiety, and stress in Polish patients with SIBO.
Methodology:
This study included 26 patients with SIBO aged 20-35 years and 24 non-SIBO patients aged 20-35 years. The following instruments were used: NEO-FFI Personality Inventory, KPS Sense of Stress Questionnaire, and the anxiety-state subscale from the State-Trait Anxiety Inventory (STAI).
Results:
Compared to the non-SIBO subgroup, SIBO patients expressed specific patterns of personality traits: higher neuroticism, lower extroversion, and a higher state of anxiety and stress. Unlike the non-SIBO subgroup, stress (total emotional tension, external, and intrapsychic) correlated negatively only with extroversion.
Conclusions:
Personality is the primary regulator of experience and behavior. The specificity captured in the research is a premise for an in-depth study considering various psychological variables to determine cause-effect relationships.
... Moreover, through the action of various microbial gene products, metabolites, and multiple microbial structural components, this microbiota performs an essential role in regulating host immunity, metabolic activity, intestinal homeostasis, and gut barrier function. Microbial dysbiosis is mainly associated with various intestinal abnormalities such as Inflammatory Bowel Disease (IBD) and colorectal cancer [6]. In this regard, E. coli capable of adhering to intestinal epithelial cells also carries numerous toxins, named cyclomodulins that include colibactin, cytolethal distending toxin (CDT), cycle inhibiting factor, and cytotoxic necrotizing factor (CNF), have been reported from CRC patients. ...
Colorectal cancer (CRC) is the third most prevalent cause of tumorigenesis and several pathogenic bacteria have been correlated with aggressive cases of cancer i.e., genotoxin (colibactin) producing Escherichia coli ( E . coli) . This study was designed to investigate the genetic diversity of clb ⁺ clb ⁺ E . coli strains and their association with CRC. Pathogenic E . coli isolates from colorectal biopsies were characterized based on phylotypes, antibiotic resistance pattern, and (Enterobacterial Repetitive Intergenic Consensus Sequence-based Polymerase Chain Reaction) ERIC-PCR. Furthermore, isolates were screened for the presence of the Pks (polyketide synthase) Island specifically targeting colibactin genes A and Q. The selective clb ⁺ clb ⁺ isolates were subjected to cytotoxicity assay using Human embryonic kidney (HEK) cell lines. We revealed that 43.47% of the cancer-associated E . coli isolates were from phylogroup B2 comparatively more pathogenic than rest while in the case of healthy controls no isolate was found from B2. Moreover, 90% were found positive for colibactin and pks (polyketide synthase) island, while none of the healthy controls were found positive for colibactin genes. All healthy and cancer-associated isolates were tested against 15 antibiotic agents, we observed that cancer-associated isolates showed a wide range of resistance from 96% against Nalidixic acid to 48% against Doxycycline. Moreover, E . coli isolates were further genotyped using ERIC-PCR, and selected clb ⁺ clb ⁺ E . coli isolates were subjected to cytotoxicity assay. We recorded the significant cytotoxic activity of clb+clb+ E . coli phylogroup B2 isolates that might have contributed towards the progression of CRC or dysbiosis of healthy gut microbiota protecting against CRC pathogenesis. Our results revealed a significant p <0.023 association of dietary habits and hygiene p <0.001with CRC. This is the first study to report the prevalence of E . coli phylogroups and the role of colibactin most virulent phylogroup B2 among Pakistani individuals from low socioeconomic setup.
... These mutants grew as well as wild type (S2 Fig), showing that attenuation of the killing phenotype was not due to growth differences. Although co-culture with E. coli Δpks did not restore S. aureus growth to single species growth levels, S. aureus CFU were similar to that in co-culture with E. coli MG1655 (Fig 1C) which does not possess the pks island [34,35] and which also failed to kill S. aureus. We therefore surmise that nutrient competition within mixed species macrocolonies results in a 1-2 log decrease in S. aureus compared to S. aureus grown alone. ...
Wound infections are often polymicrobial in nature, biofilm associated and therefore tolerant to antibiotic therapy, and associated with delayed healing. Escherichia coli and Staphylococcus aureus are among the most frequently cultured pathogens from wound infections. However, little is known about the frequency or consequence of E . coli and S . aureus polymicrobial interactions during wound infections. Here we show that E . coli kills Staphylococci, including S . aureus , both in vitro and in a mouse excisional wound model via the genotoxin, colibactin. Colibactin biosynthesis is encoded by the pks locus, which we identified in nearly 30% of human E . coli wound infection isolates. While it is not clear how colibactin is released from E . coli or how it penetrates target cells, we found that the colibactin intermediate N-myristoyl-D-Asn (NMDA) disrupts the S . aureus membrane. We also show that the BarA-UvrY two component system (TCS) senses the environment created during E . coli and S . aureus mixed species interaction, leading to upregulation of pks island genes. Further, we show that BarA-UvrY acts via the carbon storage global regulatory (Csr) system to control pks expression. Together, our data demonstrate the role of colibactin in interspecies competition and show that it is regulated by BarA-UvrY TCS during interspecies competition.
... The intestinal microbiota plays a key role in the nutrition, metabolism, and physiological characteristics of the intestine (e.g., proliferation and differentiation of intestinal epithelial cells, pH, function), in the development of the immune system, and in protecting from pathogens [39,40]. Carbohydrate fermentation is a key activity of the gut microbiota, which aims to produce energy and carbon molecules for the large intestine. ...
The use of innovative approaches to elucidate the pathophysiological mechanisms of autoimmune diseases, as well as to further study of the factors which can have either a positive or negative effect on the course of the disease, is essential. In this line, the development of new molecular techniques and the creation of the Human Genome Program have allowed access to many more solutions to the difficulties that exist in the identification and characterization of the microbiome, as well as changes due to various factors. Such innovative technologies can rekindle older hypotheses, such as molecular mimicry, allowing us to move from hypothesis to theory and from correlation to causality, particularly regarding autoimmune diseases and dysbiosis of the microbiota. For example, Prevotella copri appears to have a strong association with rheumatoid arthritis; it is expected that this will be confirmed by several scientists, which, in turn, will make it possible to identify other mechanisms that may contribute to the pathophysiology of the disease. This article seeks to identify new clues regarding similar correlations between autoimmune activity and the human microbiota, particularly in relation to qualitative and quantitative microbial variations therein.
... We also observed that the abundance of Firmicutes was significantly reduced after starvation. Most studies have demonstrated that this phylum plays a pathogenic role in enteritis and colon cancer (Yang and Jobin, 2014). In the intestinal tract of an inflammation mouse model, the significantly increased abundance of Proteobacteria reflected a decrease in the permeability of intestinal epithelium and dysregulation of the innate immune response leading to host flora disorder (Na-Ri et al., 2015). ...
Obesity is a serious public health problem. Short-term starvation is an effective way to lose weight but can also cause harm to the body. However, a systematic assessment of the relationship between the intestinal microbiota and metabolites after complete fasting is lacking. Pigs are the best animal models for exploring the mechanisms of human nutrition digestion and absorption, metabolism, and disease treatment. In this study, 16S rRNA sequencing and liquid chromatography-mass spectrometry were used to analyze the changes in the intestinal microbiota and metabolite profiles in piglets under starvation stress. The results show that the microbial composition was changed significantly in the starvation groups compared with the control group (P < 0.05), suggesting that shifts in the microbial composition were induced by starvation stress. Furthermore, differences in the correlation of the intestinal microbiota and metabolites were observed in the different experimental groups. Starvation may disrupt the homeostasis of the intestinal microbiota and metabolite profile and affect the health of piglets. However, piglets can regulate metabolite production to compensate for the effects of short-term starvation. Our results provide a background to explore the mechanism of diet and short-term hunger for intestinal homeostasis.
... Rho GTPase-activating protein 5 promotes EMT to accelerate tumor metastasis by regulating RhoA activity in CRC cells (41), which corroborated the results of the present study of LIMK1 enrichment in MF. Axon guidance (42), regulation of actin cytoskeleton (43) and pathogenic E. coli infection (44) pathways are involved in the process of the occurrence of metastasis in CRC. Therefore, combined with the results of the present study, it was hypohesized that the upregulated LIMK1 might directly or indirectly affect the biological functions of tumors by regulating these proteins and pathways. ...
Studies have shown that LIM domain kinase 1 (LIMK1) is upregulated in a variety of tumors and may be a potential detection target. The present study analyzed the expression difference of LIMK1 and its relationship with tumor clinicopathological characteristics and tumor microenvironment in colorectal cancer (CRC). The transcriptomic data of LIMK1 with CRC were downloaded from The Cancer Genome Atlas (TCGA) database and GEO databases for analyzing the expression of LIMK1 mRNA and the correlation with the prognosis of patients. The protein expression of LIMK1 was obtained from the Human Protein Atlas. The receiver operating characteristic (ROC) curve and Kaplan-Meier was used to evaluate the expression characteristics and prognostic differences of LIMK1 in CRC. STRING was used to analyze co-expression genes of LIMK1. The tumor immune estimation resource was applied to the correlation between LIMK1 expression and immune infiltrates. The present study verified LIMK1 expression at the level of clinical samples collected from the Tianjin Medical University General Hospital and cell lines using reverse transcription-quantitative PCR. The mRNA and protein expression of LIMK1 were both upregulated in tumor tissues compared with adjacent tissues in CRC. The expression levels of LIMK1 were positively associated with clinical-pathological features of CRC including lymphatic invasion (P=4.00×10-2) and high pathologic stages (P=4.20×10-2). The AUC value of LIMK1 in CRC was 0.937 (95% CI: 0.918-0.957) through ROC analysis. Under the best cut-off value (4.009), the sensitivity and specificity were 98 and 81.9%. LIMK1 expression was mainly related to CD4+ T cells, macrophages and dendritic cells in the immune microenvironment of CRC. In conclusion, the high expression of LIMK1 in CRC was closely related to the clinical features and prognosis of patients. Therefore, LIMK1 was a promising prognostic indicator and a potential target for immunotherapy in CRC.
