Oral bacteria affect the gut microbiome and intestinal immunity

2020 ◽  
Vol 78 (3) ◽  
Author(s):  
Ryoki Kobayashi ◽  
Yasuhiro Ogawa ◽  
Tomomi Hashizume-Takizawa ◽  
Tomoko Kurita-Ochiai
Keyword(s):  
Oral Administration ◽  
Bacterial Infection ◽  
Th17 Cells ◽  
Intestinal Barrier ◽  
Oral Bacteria ◽  
Intestinal Barrier Function ◽  
M2 Macrophage ◽  
Oral Streptococci ◽  
Intestinal Immunity ◽  
Gut Dysbiosis

ABSTRACT Recently, it has been suggested that the oral administration of Porphyromonas gingivalis, a keystone pathogen for periodontal disease, induces dysbiosis of the mouse intestinal microbiota and affects intestinal barrier function. Since oral streptococci are the predominant oral bacterial group, we compared the effect of their oral administration on the intestinal tract compared to that of P. gingivalis. Swallowing oral bacteria caused gut dysbiosis, due to increased Bacteroides and Staphylococcus and decreased Lactobacillus spp. Furthermore, oral bacterial infection caused an increase in lactate and decreases in succinate and n-butyrate contents. In the small intestine, the decrease in Th17 cells was considered to be a result of oral bacterial infection, although the population of Treg cells remained unaffected. In addition, oral bacterial challenge increased the M1/M2 macrophage ratio and decreased the immunoglobulin A (IgA) antibody titer in feces. These results suggest that gut dysbiosis caused by oral bacteria may cause a decrease in Th17 cells and fecal IgA levels and an increase in the M1/M2 macrophage ratio, thereby promoting chronic inflammation.

scholarly journals A54 THE CIRCADIAN CLOCK INFLUENCES JAK/STAT SIGNALING AND GUT PERMEABILITY

2021 ◽  
Vol 4 (Supplement_1) ◽  
pp. 11-12
Author(s):  
K Parasram ◽  
D Bachetti ◽  
P Karpowicz
Keyword(s):  
Circadian Clock ◽  
Clock Cycle ◽  
Intestinal Barrier ◽  
Fruit Fly ◽  
Cell Types ◽  
Time Of Day ◽  
Acute Injury ◽  
Intestinal Barrier Function ◽  
Intestinal Immunity ◽  
Stat Signaling

Abstract Background The circadian clock is a 24-hour feedback loop that drives rhythms in behaviours and physiological processes. This molecular timekeeper consists of the transcription factors, Clock-Cycle, that drive expression of thousands of clock-controlled genes, with two of these, Period and Timeless, acting as negative regulators of Clock-Cycle. This fundamental mechanism was initially characterized in the fruit fly, Drosophila melanogaster (Nobel Prize in Physiology & Medicine, 2017), and is highly conserved in humans. The intestine, or midgut, of Drosophila, is also similar to the human small intestine consisting of similar cellular lineage, signaling pathways, and physiological functions. The lineage of the Drosophila intestine contains the same four cell types as humans: intestinal stem cells (ISCs), progenitors called enteroblasts, enterocytes and enteroendocrine cells. This simplified lineage as well as the genetic tools available, make Drosophila an ideal model for intestinal regeneration in health and disease. We have previously shown that the circadian clock is active in ISCs, EBs and ECs during both homeostatic and regenerating conditions. Furthermore, the circadian clock regulates the mitosis of ISCs under regenerating conditions. Aims We sought to uncover if Jak/STAT signaling, one of the key pathways involved in ISC proliferation in the Drosophila intestine, shows a circadian rhythm and if there is a time-of-day difference in the regenerative response. Methods To test whether the clock regulates Jak/STAT during acute injury, we developed an irradiation assay that does not affect survival but acutely disrupts intestinal barrier function. Results Using a dynamic reporter of Jak/STAT activity we show that Period circadian clock mutants have low Jak/STAT signaling and a leaky gut phenotype. Wildtype controls show time-dependent gut leakiness upon irradiation, which is higher and time-independent in Period mutants. The level of Jak/STAT response differs depending on the time of irradiation in the controls, but is higher at all times in the mutants. Conclusions The Jak/Stat pathway regulates intestinal immunity and epithelial cell proliferation in humans, thus playing a role in colorectal cancer and inflammatory bowel disease. Our results suggest Jak/Stat is controlled by the circadian clock, which has implications for intestinal recovery following medical treatments, including radiation therapy. Funding Agencies NRC

scholarly journals The Role of Gut Dysbiosis in the Bone–Vascular Axis in Chronic Kidney Disease

Toxins ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 285 ◽  
Author(s):  
Pieter Evenepoel ◽  
Sander Dejongh ◽  
Kristin Verbeke ◽  
Bjorn Meijers
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Mineral Density ◽  
Bone Mineral Density Loss ◽  
Gut Dysbiosis ◽  
Increased Risk ◽  
Fermentation Pattern

Patients with chronic kidney disease (CKD) are at increased risk of bone mineral density loss and vascular calcification. Bone demineralization and vascular mineralization often concur in CKD, similar to what observed in the general population. This contradictory association is commonly referred to as the ‘calcification paradox’ or the bone–vascular axis. Mounting evidence indicates that CKD-associated gut dysbiosis may be involved in the pathogenesis of the bone–vascular axis. A disrupted intestinal barrier function, a metabolic shift from a predominant saccharolytic to a proteolytic fermentation pattern, and a decreased generation of vitamin K may, alone or in concert, drive a vascular and skeletal pathobiology in CKD patients. A better understanding of the role of gut dysbiosis in the bone–vascular axis may open avenues for novel therapeutics, including nutriceuticals.

scholarly journals Prenatal Maternal Stress Exacerbates Experimental Colitis of Offspring in Adulthood

2021 ◽  
Vol 12 ◽  
Author(s):  
Yue Sun ◽  
Runxiang Xie ◽  
Lu Li ◽  
Ge Jin ◽  
Bingqian Zhou ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Barrier Function ◽  
Maternal Stress ◽  
Intestinal Barrier ◽  
Experimental Colitis ◽  
Intestinal Barrier Function ◽  
Low Grade ◽  
Prenatal Maternal Stress ◽  
Gut Dysbiosis ◽  
Mucosal Barrier Function

The prevalence of inflammatory bowel disease (IBD) is increasing worldwide and correlates with dysregulated immune response because of gut microbiota dysbiosis. Some adverse early life events influence the establishment of the gut microbiota and act as risk factors for IBD. Prenatal maternal stress (PNMS) induces gut dysbiosis and perturbs the neuroimmune network of offspring. In this study, we aimed to investigate whether PNMS increases the susceptibility of offspring to colitis in adulthood. The related index was assessed during the weaning period and adulthood. We found that PNMS impaired the intestinal epithelial cell proliferation, goblet cell and Paneth cell differentiation, and mucosal barrier function in 3-week-old offspring. PNMS induced low-grade intestinal inflammation, but no signs of microscopic inflammatory changes were observed. Although there was no pronounced difference between the PNMS and control offspring in terms of their overall measures of alpha diversity for the gut microbiota, distinct microbial community changes characterized by increases in Desulfovibrio, Streptococcus, and Enterococcus and decreases in Bifidobacterium and Blautia were induced in the 3-week-old PNMS offspring. Notably, the overgrowth of Desulfovibrio persisted from the weaning period to adulthood, consistent with the results observed using fluorescence in situ hybridization in the colon mucosa. Mechanistically, the fecal microbiota transplantation experiment showed that the gut microbiota from the PNMS group impaired the intestinal barrier function and induced low-grade inflammation. The fecal bacterial solution from the PNMS group was more potent than that from the control group in inducing inflammation and gut barrier disruption in CaCo-2 cells. After treatment with a TNF-α inhibitor (adalimumab), no statistical difference in the indicators of inflammation and intestinal barrier function was observed between the two groups. Finally, exposure to PNMS remarkably increased the values of the histopathological parameters and the inflammatory cytokine production in a mouse model of experimental colitis in adulthood. These findings suggest that PNMS can inhibit intestinal development, impair the barrier function, and cause gut dysbiosis characterized by the persistent overgrowth of Desulfovibrio in the offspring, resulting in exacerbated experimental colitis in adulthood.

scholarly journals Gut Dysbiosis and Intestinal Barrier Dysfunction: Potential Explanation for Early-Onset Colorectal Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Siti Maryam Ahmad Kendong ◽  
Raja Affendi Raja Ali ◽  
Khairul Najmi Muhammad Nawawi ◽  
Hajar Fauzan Ahmad ◽  
Norfilza Mohd Mokhtar
Keyword(s):  
Colorectal Cancer ◽  
Environmental Factors ◽  
Gut Microbiota ◽  
Early Onset ◽  
Early Stage ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Gut Dysbiosis ◽  
Early Onset Colorectal Cancer

Colorectal cancer (CRC) is a heterogeneous disease that commonly affects individuals aged more than 50 years old globally. Regular colorectal screening, which is recommended for individuals aged 50 and above, has decreased the number of cancer death toll over the years. However, CRC incidence has increased among younger population (below 50 years old). Environmental factors, such as smoking, dietary factor, urbanization, sedentary lifestyle, and obesity, may contribute to the rising trend of early-onset colorectal cancer (EOCRC) because of the lack of genetic susceptibility. Research has focused on the role of gut microbiota and its interaction with epithelial barrier genes in sporadic CRC. Population with increased consumption of grain and vegetables showed high abundance of Prevotella, which reduces the risk of CRC. Microbes, such as Fusobacterium nucleatum, Bacteroides fragilis and Escherichia coli deteriorate in the intestinal barrier, which leads to the infiltration of inflammatory mediators and chemokines. Gut dysbiosis may also occur following inflammation as clearly observed in animal model. Both gut dysbiosis pre- or post-inflammatory process may cause major alteration in the morphology and functional properties of the gut tissue and explain the pathological outcome of EOCRC. The precise mechanism of disease progression from an early stage until cancer establishment is not fully understood. We hypothesized that gut dysbiosis, which may be influenced by environmental factors, may induce changes in the genome, metabolome, and immunome that could destruct the intestinal barrier function. Also, the possible underlying inflammation may give impact microbial community leading to disruption of physical and functional role of intestinal barrier. This review explains the potential role of the interaction among host factors, gut microenvironment, and gut microbiota, which may provide an answer to EOCRC.

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