scholarly journals Intestinal microbiota as part of normal physiology of the host

2016 ◽  
Vol 72 (9) ◽  
pp. 536-541
Author(s):  
Marian Binek ◽  
Magdalena Rzewuska ◽  
Magdalena Kizerwetter-Świda ◽  
Dorota Chrobak-Chmiel ◽  
Małgorzata Gieryńska ◽  
...  

The gastrointestinal tract in humans and animals contains a very large number of highly diverse microorganisms. This microbiota plays a major role in the host’s physiology, homeostasis, and well-being. It forms a barrier against infection, helps to develop and mature the immune system, and participates in the extraction of nutrients and energy from food. Various members of microbial community maintain the integrity of the intestinal barrier and promote epithelial repair after injury. The intestinal barrier defenses consist of the mucous layer, antimicrobial peptides, secretory IgA, and the epithelial barrier function by junctional adhesion complex. A healthy host exists in a state of balance with its microorganisms. A disruption of the microbial community increases the host’s susceptibility to infection. Although the immune response is necessary for the host to eliminate the invading pathogen, certain aspects of the host’s response may work to the pathogen’s advantage. Certain components of the microbiota have been shown to drive inflammatory response, which, if uncontrolled, has the potential to induce a pathological response, whereas others enhance or promote anti-inflammatory responses. The effector microbial molecules are usually detected via receptor-signaling pathways including Toll-like receptors, NOD-like receptors, and C-type lectin receptors. These pattern-recognition receptors (PRRs) interact with and identify microbe-associated molecular patterns (MAMPs) of both commensal and pathogenic bacteria. PRRs signaling, once thought to exclusively yield pro-inflammatory activation by pathogenic bacteria, is now known to be differentially activated by commensal and probiotic bacteria to induce pathways involved in gut homeostasis, cytoprotection, epithelial cell proliferation, regulation of tight junctions, and antimicrobial peptide secretion. The microbial-epithelial cross-talk is fundamental in appreciating how the developing intestine achieves tolerance to bacteria and how dysregulation of this process may predispose the gut to inflammation and disease.

2012 ◽  
Vol 109 (11) ◽  
pp. 1971-1979 ◽  
Author(s):  
Eva Velez ◽  
Natalia Castillo ◽  
Oscar Mesón ◽  
Alfredo Grau ◽  
María E. Bibas Bonet ◽  
...  

Beneficial effects of prebiotics like inulin and fructo-oligosaccharides (FOS) have been proven in health and nutrition. Yacon (Smallanthus sonchifolius), an Andean crop, contains FOS (50–70 % of its dry weight) and, therefore, is considered a prebiotic. Commercial FOS can up-regulate total secretory IgA (S-IgA) in infant mice, prevent infection with Salmonella in swine or enhance immune response for Salmonella vaccine in a mouse model. Previously, we found that administration of yacon root flour regulates gut microbiota balance and has immunomodulatory effects without inflammatory responses. The aim of the present paper is to analyse if yacon prevents enteric infection caused by a strain of Salmonella enteritidis serovar Typhimurium (S. Typhimurium) in a mouse model. BALB/c mice were supplemented with yacon flour (45 d), challenged with S. Typhimurium and killed to study pathogen translocation, total and specific IgA production by ELISA, presence of IgA and other cytokines and Toll-like receptor 4 (TLR4) and clustor of differentiation 206 (CD206) receptors positive cells by immunofluorescence and histological changes. Yacon flour administration had a protective effect from 15 to 30 d of treatment. We found a peak of total S-IgA production without translocation of the pathogen for these periods. At 30 d, there was an increase in IL-6 and macrophage inflammatory proteins-1α+ cells and expression of the receptors CD206 and TLR4. Yacon flour did not have incidence in pathogen-specific S-IgA production. Longer periods (45 d) of administration had no protective effect. Therefore, yacon can prevent enteric infection caused by S. Typhimurium when given up to 30 d; this effect would be mediated by enhancing non-specific immunity, such as total S-IgA, that improves the immunological intestinal barrier.


2016 ◽  
Vol 72 (10) ◽  
pp. 611-615 ◽  
Author(s):  
Marian Binek ◽  
Magdalena Kizerwetter-Świda ◽  
Agata Anna Cisek ◽  
Magdalena Rzewuska ◽  
Dorota Chrobak-Chmiel ◽  
...  

Intestinal microbes are taxonomically diverse and constitute an ecologically dynamic microbiom interactively performing various physiological and physiopathological processes. It has been proposed that normal intestinal microbiotas play a critical role in the host’s metabolic homeostasis and immune tolerance. The modulation of intestinal microbiota populations by prebiotics, probiotics, and synbiotics may be beneficial for the host’s health. Under certain conditions, the intestinal microbiota and the host’s homeostasis can be restored by introducing bacteria that co-mediate anti-inflammatory responses. Commensal microbes and probiotics exert their beneficial effect by at least three mechanisms. These include - the maintenance of the epithelial barrier function and the attenuation of changes in intestinal permeability through effects on tight junction, decreasing paracellular permeability, providing innate defense against pathogens, and enhancing the physical impediment of the mucous layer, - competitive exclusion by the application of probiotic bacteria stabilizing the indigenous microflora, - immunomodulatory capacity, affecting a variety of signaling pathways with modulation of proper immune, inflammatory and allergic responses. The epithelial gut barrier faces important challenges, since its function is to prevent pathogens and harmful elements of the gut lumen from penetrating into the internal environment. Competitive exclusion treatment can increase resistance to pathogen colonization and control intestinal disturbance. The dominance of symbiotic and probiotic bacteria among the gut microbiota favors a tolerogenic immune response. The release of secretory IgA stabilizes tight junctions between cells of the epithelial layer as well as hampers pathogens and symbionts invading deeper layers. The understanding of these vital processes may help to protect the host against infection, prevent chronic inflammation, and maintain mucosal integrity.


2010 ◽  
Vol 298 (6) ◽  
pp. G807-G819 ◽  
Author(s):  
Christina L. Ohland ◽  
Wallace K. MacNaughton

The intestinal tract is a diverse microenvironment where more than 500 species of bacteria thrive. A single layer of epithelium is all that separates these commensal microorganisms and pathogens from the underlying immune cells, and thus epithelial barrier function is a key component in the arsenal of defense mechanisms required to prevent infection and inflammation. The epithelial barrier consists of a dense mucous layer containing secretory IgA and antimicrobial peptides as well as dynamic junctional complexes that regulate permeability between cells. Probiotics are live microorganisms that confer benefit to the host and that have been suggested to ameliorate or prevent diseases including antibiotic-associated diarrhea, irritable bowel syndrome, and inflammatory bowel disease. Probiotics likely function through enhancement of barrier function, immunomodulation, and competitive adherence to the mucus and epithelium. This review summarizes the evidence about effects of the many available probiotics with an emphasis on intestinal barrier function and the mechanisms affected by probiotics.


2020 ◽  
Vol 295 (30) ◽  
pp. 10493-10505 ◽  
Author(s):  
Rashi Singhal ◽  
Yatrik M. Shah

The gastrointestinal tract is a highly proliferative and regenerative tissue. The intestine also harbors a large and diverse microbial population collectively called the gut microbiome (microbiota). The microbiome–intestine cross-talk includes a dynamic exchange of gaseous signaling mediators generated by bacterial and intestinal metabolisms. Moreover, the microbiome initiates and maintains the hypoxic environment of the intestine that is critical for nutrient absorption, intestinal barrier function, and innate and adaptive immune responses in the mucosal cells of the intestine. The response to hypoxia is mediated by hypoxia-inducible factors (HIFs). In hypoxic conditions, the HIF activation regulates the expression of a cohort of genes that promote adaptation to hypoxia. Physiologically, HIF-dependent genes contribute to the aforementioned maintenance of epithelial barrier function, nutrient absorption, and immune regulation. However, chronic HIF activation exacerbates disease conditions, leading to intestinal injury, inflammation, and colorectal cancer. In this review, we aim to outline the major roles of physiological and pathological hypoxic conditions in the maintenance of intestinal homeostasis and in the onset and progression of disease with a major focus on understanding the complex pathophysiology of the intestine


2011 ◽  
Vol 18 (4) ◽  
pp. 621-628 ◽  
Author(s):  
Theo S. Plantinga ◽  
Wendy W. C. van Maren ◽  
Jeroen van Bergenhenegouwen ◽  
Marjolijn Hameetman ◽  
Stefan Nierkens ◽  
...  

ABSTRACTThe use of probiotics as a food supplement has gained tremendous interest in the last few years as beneficial effects were reported in gut homeostasis and nutrient absorption but also in immunocompromised patients, supporting protection from colonization or infection with pathogenic bacteria or fungi. As a treatment approach for inflammatory bowel diseases, a suitable probiotic strain would ideally be one with a low immunogenic potential. Insight into the immunogenicities and types of T-cell responses induced by potentially probiotic strains allows a more rational selection of a particular strain. In the present study, the bacterial strainsBifidobacterium breve(NumRes 204),Lactobacillus rhamnosus(NumRes1), andLactobacillus casei(DN-114 001) were compared concerning their capacity to induce inflammatory responses in terms of cytokine production by human and mouse primary immune cells. It was demonstrated that theB. brevestrain induced lower levels of the proinflammatory cytokine gamma interferon (IFN-γ) than the testedL. rhamnosusandL. caseistrains. BothB. breveand lactobacilli induced cytokines in a Toll-like receptor 9 (TLR9)-dependent manner, while the lower inflammatory profile ofB. brevewas due to inhibitory effects of TLR2. No role for TLR4, NOD2, and C-type lectin receptors was apparent. In conclusion, TLR signaling is involved in the differentiation of inflammatory responses between probiotic strains used as food supplements.


2010 ◽  
Vol 80 (45) ◽  
pp. 279-292 ◽  
Author(s):  
Richard Hurrell

Febrile malaria and asymptomatic malaria parasitemia substantially decrease iron absorption in single-meal, stable isotope studies in women and children, but to date there is no evidence of decreased efficacy of iron-fortified foods in malaria-endemic regions. Without inadequate malarial surveillance or health care, giving iron supplements to children in areas of high transmission could increase morbidity and mortality. The most likely explanation is the appearance of non-transferrin-bound iron (NTBI) in the plasma. NTBI forms when the rate of iron influx into the plasma exceeds the rate of iron binding to transferrin. Two studies in women have reported substantially increased NTBI with the ingestion of iron supplements. Our studies confirm this, but found no significant increase in NTBI on consumption of iron-fortified food. It seems likely that the malarial parasite in hepatocytes can utilize NTBI, but it cannot do so in infected erythrocytes. NTBI however may increase the sequestration of parasite-infected erythrocytes in capillaries. Bacteremia is common in children with severe malaria and sequestration in villi capillaries could lead to a breaching of the intestinal barrier, allowing the passage of pathogenic bacteria into the systemic circulation. This is especially important as frequent high iron doses increase the number of pathogens in the intestine at the expense of the barrier bacteria.


2020 ◽  
Vol 11 ◽  
Author(s):  
Runze Quan ◽  
Chaoyue Chen ◽  
Wei Yan ◽  
Ying Zhang ◽  
Xi Zhao ◽  
...  

B cell-activating factor (BAFF) production is increased in septic patients. However, the specific role of BAFF in sepsis remains unknown. This study was designed to investigate the expression and function of BAFF in an experimental endotoxemia model and to identify the potential mechanisms. We established an endotoxemia mouse (6–8 weeks, 20–22 g) model by administering 30 mg/kg lipopolysaccharide (LPS). BAFF levels in the circulating system and organ tissues were measured 4 and 8 h after LPS injection. Survival rates in the endotoxemia mice were monitored for 72 h after BAFF blockade. The effects of BAFF blockade on systemic and local inflammation, organ injuries, and intestinal barrier function were also evaluated 4 h after LPS treatment. BAFF production was systemically and locally elevated after LPS challenge. BAFF blockade improved the survival rate, systemic inflammation, and multi-organ injuries. Moreover, BAFF blockade attenuated both intestinal inflammation and impaired intestinal permeability. BAFF blockade upregulated ZO-1 and occludin protein levels via the NF-κB/MLCK/MLC signaling pathway. These results suggested that BAFF blockade protects against lethal endotoxemia at least partially by alleviating inflammation, multi-organ injuries, and improving intestinal barrier function and provides a novel focus for further research on sepsis and experimental evidence for clinical therapy.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nathaniel B. Bone ◽  
Eugene J. Becker ◽  
Maroof Husain ◽  
Shaoning Jiang ◽  
Anna A. Zmijewska ◽  
...  

AbstractMetabolic and bioenergetic plasticity of immune cells is essential for optimal responses to bacterial infections. AMPK and Parkin ubiquitin ligase are known to regulate mitochondrial quality control mitophagy that prevents unwanted inflammatory responses. However, it is not known if this evolutionarily conserved mechanism has been coopted by the host immune defense to eradicate bacterial pathogens and influence post-sepsis immunosuppression. Parkin, AMPK levels, and the effects of AMPK activators were investigated in human leukocytes from sepsis survivors as well as wild type and Park2−/− murine macrophages. In vivo, the impact of AMPK and Parkin was determined in mice subjected to polymicrobial intra-abdominal sepsis and secondary lung bacterial infections. Mice were treated with metformin during established immunosuppression. We showed that bacteria and mitochondria share mechanisms of autophagic killing/clearance triggered by sentinel events that involve depolarization of mitochondria and recruitment of Parkin in macrophages. Parkin-deficient mice/macrophages fail to form phagolysosomes and kill bacteria. This impairment of host defense is seen in the context of sepsis-induced immunosuppression with decreased levels of Parkin. AMPK activators, including metformin, stimulate Parkin-independent autophagy and bacterial killing in leukocytes from post-shock patients and in lungs of sepsis-immunosuppressed mice. Our results support a dual role of Parkin and AMPK in the clearance of dysfunctional mitochondria and killing of pathogenic bacteria, and explain the immunosuppressive phenotype associated Parkin and AMPK deficiency. AMPK activation appeared to be a crucial therapeutic target for the macrophage immunosuppressive phenotype and to reduce severity of secondary bacterial lung infections and respiratory failure.


2021 ◽  
Vol 10 (15) ◽  
pp. 3258
Author(s):  
Cristina Oana Mărginean ◽  
Lorena Elena Meliț ◽  
Maria Oana Săsăran

Helicobacter pylori (H. pylori) carcinogenicity depends on three major factors: bacterial virulence constituents, environmental factors and host’s genetic susceptibility. The relationship between microenvironmental factors and H. pylori virulence factors are incontestable. H. pylori infection has a major impact on both gastric and colonic microbiota. The presence of non-H. pylori bacteria within the gastric ecosystem is particularly important since they might persistently act as an antigenic stimulus or establish a partnership with H. pylori in order to augment the subsequent inflammatory responses. The gastric ecosystem, i.e., microbiota composition in children with H. pylori infection is dominated by Streptoccocus, Neisseria, Rothia and Staphylococcus. The impairment of this ecosystem enhances growth and invasion of different pathogenic bacteria, further impairing the balance between the immune system and mucosal barrier. Moreover, altered microbiota due to H. pylori infection is involved in increasing the gastric T regulatory cells response in children. Since gastric homeostasis is defined by the partnership between commensal bacteria and host’s immune system, this review is focused on how pathogen recognition through toll-like receptors (TLRs—an essential class of pathogen recognition receptors—PRRs) on the surface of macrophages and dendritic cells impact the immune response in the setting of H. pylori infection. Further studies are required for delineate precise role of bacterial community features and of immune system components.


Amino Acids ◽  
2021 ◽  
Author(s):  
Tatsuya Hasegawa ◽  
Ami Mizugaki ◽  
Yoshiko Inoue ◽  
Hiroyuki Kato ◽  
Hitoshi Murakami

AbstractIntestinal oxidative stress produces pro-inflammatory cytokines, which increase tight junction (TJ) permeability, leading to intestinal and systemic inflammation. Cystine (Cys2) is a substrate of glutathione (GSH) and inhibits inflammation, however, it is unclear whether Cys2 locally improves intestinal barrier dysfunction. Thus, we investigated the local effects of Cys2 on oxidative stress-induced TJ permeability and intestinal inflammatory responses. Caco-2 cells were cultured in a Cys2-supplemented medium for 24 h and then treated with H2O2 for 2 h. We assessed TJ permeability by measuring transepithelial electrical resistance and the paracellular flux of fluorescein isothiocyanate–dextran 4 kDa. We measured the concentration of Cys2 and GSH after Cys2 pretreatment. The mRNA expression of pro-inflammatory cytokines was assessed. In addition, the levels of TJ proteins were assessed by measuring the expression of TJ proteins in the whole cells and the ratio of TJ proteins in the detergent-insoluble fractions to soluble fractions (IS/S ratio). Cys2 treatment reduced H2O2-induced TJ permeability. Cys2 did not change the expression of TJ proteins in the whole cells, however, suppressed the IS/S ratio of claudin-4. Intercellular levels of Cys2 and GSH significantly increased in cells treated with Cys2. Cys2 treatment suppressed the mRNA expression of pro-inflammatory cytokines, and the mRNA levels were significantly correlated with TJ permeability. In conclusion, Cys2 treatment locally reduced oxidative stress-induced intestinal barrier dysfunction possively due to the mitigation of claudin-4 dislocalization. Furthermore, the effect of Cys2 on the improvement of intestinal barrier function is related to the local suppression of oxidative stress-induced pro-inflammatory responses.


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