scholarly journals The Gut Microbiota is Associated with the Small Intestinal Paracellular Permeability and the Development of the Immune System in Healthy Children During the First Two Years of Life

Author(s):  
Mariusz Kaczmarczyk ◽  
Ulrike Löber ◽  
Karolina Adamek ◽  
Dagmara Węgrzyn ◽  
Karolina Skonieczna-Żydecka ◽  
...  

Abstract BackgroundThe intestinal barrier plays an important role in the defense against infections, and nutritional, endocrine, and immune functions. The gut microbiota playing important role in development of the gastrointestinal tract can impact intestinal permeability and immunity during early life, but data concerning this problem are scare.MethodsWe analyzed the microbiota in fecal samples (101 samples in total) collected longitudinally over 24 months from 21 newborns to investigate whether the markers of small intestinal paracellular permeability (zonulin) and immune system development (calprotectin) are linked to the gut microbiota. The results were validated using data from an independent cohort that included the calprotectin and gut microbiota in children during the first year of life. ResultsZonulin levels tended to increase for up to 6 months after childbirth and stabilize thereafter remaining at a high level while calprotectin concentration was high after chilbirth and begun to decline from 6 months of life. The gut microbiota composition and the related metabolic potentials changed during the first two years of life and were correlated with zonulin and calprotectin levels. Feacal calprotectin correlated inversely with alpha diversity (Shannon index, r =-0.30, FDR P (Q)=0.039). It also correlated with seven taxa; i.a. negatively with Ruminococccaceae (r=-0.34, Q=0.046), and Clostridiales (r=-0.34, Q=0.048) and positively with Stapylococcus (r=0.38, Q=0.023) and Staphylococcaceae (r=0.35, Q=0.04), whereas zonulin correlated with 19 taxa; i.a. with Bacillales (r=-0.52, Q=0.0004), Clostridiales (r=0.48, Q=0.001) and the Ruminococcus (torques group) (r=0.40, Q=0.026). When time intevals were considered only changes in abundance of the Ruminococcus (torques group) were associcated with changes in calprotectin (β=2.94, SE=0.8, Q=0.015). The dynamics of stool calprotectin was negatively associated with changes in two MetaCyc pathways: pyruvate fermentation to butanoate (β=-4.54, SE=1.08, Q=0.028) and Clostridium acetobutylicum fermentation (β=-4.48, SE=1.16, Q=0.026). ConclusionsThe small intestinal paracellular permeability, immune system-related markers and gut microbiota change dynamically during the first two years of life. The Ruminococcus (torques group) seems to be especially involved in controlling paracellular permeability. Staphylococcus, Staphylococcaceae, Ruminococcaceae, and Clostridiales, may be potential biomarkers of the immune system. Despite observed correlations their clear causation and health consequences were not proven. Mechanistic studies are required.

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Mariusz Kaczmarczyk ◽  
Ulrike Löber ◽  
Karolina Adamek ◽  
Dagmara Węgrzyn ◽  
Karolina Skonieczna-Żydecka ◽  
...  

Abstract Background The intestinal barrier plays an important role in the defense against infections, and nutritional, endocrine, and immune functions. The gut microbiota playing an important role in development of the gastrointestinal tract can impact intestinal permeability and immunity during early life, but data concerning this problem are scarce. Methods We analyzed the microbiota in fecal samples (101 samples in total) collected longitudinally over 24 months from 21 newborns to investigate whether the markers of small intestinal paracellular permeability (zonulin) and immune system development (calprotectin) are linked to the gut microbiota. The results were validated using data from an independent cohort that included the calprotectin and gut microbiota in children during the first year of life. Results Zonulin levels tended to increase for up to 6 months after childbirth and stabilize thereafter remaining at a high level while calprotectin concentration was high after childbirth and began to decline from 6 months of life. The gut microbiota composition and the related metabolic potentials changed during the first 2 years of life and were correlated with zonulin and calprotectin levels. Faecal calprotectin correlated inversely with alpha diversity (Shannon index, r = − 0.30, FDR P (Q) = 0.039). It also correlated with seven taxa; i.a. negatively with Ruminococcaceae (r = − 0.34, Q = 0.046), and Clostridiales (r = − 0.34, Q = 0.048) and positively with Staphylococcus (r = 0.38, Q = 0.023) and Staphylococcaceae (r = 0.35, Q = 0.04), whereas zonulin correlated with 19 taxa; i.a. with Bacillales (r = − 0.52, Q = 0.0004), Clostridiales (r = 0.48, Q = 0.001) and the Ruminococcus (torques group) (r = 0.40, Q = 0.026). When time intervals were considered only changes in abundance of the Ruminococcus (torques group) were associated with changes in calprotectin (β = 2.94, SE = 0.8, Q = 0.015). The dynamics of stool calprotectin was negatively associated with changes in two MetaCyc pathways: pyruvate fermentation to butanoate (β = − 4.54, SE = 1.08, Q = 0.028) and Clostridium acetobutylicum fermentation (β = − 4.48, SE = 1.16, Q = 0.026). Conclusions The small intestinal paracellular permeability, immune system-related markers and gut microbiota change dynamically during the first 2 years of life. The Ruminococcus (torques group) seems to be especially involved in controlling paracellular permeability. Staphylococcus, Staphylococcaceae, Ruminococcaceae, and Clostridiales, may be potential biomarkers of the immune system. Despite observed correlations their clear causation and health consequences were not proven. Mechanistic studies are required. Graphic abstract


Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 699
Author(s):  
Cielo García-Montero ◽  
Oscar Fraile-Martínez ◽  
Ana M. Gómez-Lahoz ◽  
Leonel Pekarek ◽  
Alejandro J. Castellanos ◽  
...  

The most prevalent diseases of our time, non-communicable diseases (NCDs) (including obesity, type 2 diabetes, cardiovascular diseases and some types of cancer) are rising worldwide. All of them share the condition of an “inflammatory disorder”, with impaired immune functions frequently caused or accompanied by alterations in gut microbiota. These multifactorial maladies also have in common malnutrition related to physiopathology. In this context, diet is the greatest modulator of immune system–microbiota crosstalk, and much interest, and new challenges, are arising in the area of precision nutrition as a way towards treatment and prevention. It is a fact that the westernized diet (WD) is partly responsible for the increased prevalence of NCDs, negatively affecting both gut microbiota and the immune system. Conversely, other nutritional approaches, such as Mediterranean diet (MD), positively influence immune system and gut microbiota, and is proposed not only as a potential tool in the clinical management of different disease conditions, but also for prevention and health promotion globally. Thus, the purpose of this review is to determine the regulatory role of nutritional components of WD and MD in the gut microbiota and immune system interplay, in order to understand, and create awareness of, the influence of diet over both key components.


Author(s):  
Yoshihiro Tomizawa ◽  
Shunya Kurokawa ◽  
Daiki Ishii ◽  
Katsuma Miyaho ◽  
Chiharu Ishii ◽  
...  

Abstract Background The antibacterial effects of psychotropics may be part of their pharmacological effects when treating depression. However, limited studies have focused on gut microbiota in relation to prescribed medication. Method We longitudinally investigated the relationship between patients’ prescribed medications and intestinal bacterial diversity in a naturalistic treatment course for patients with major depressive disorders and anxiety disorders. Patients were recruited and their stool was collected at 3 time points during their usual psychiatric treatments. Gut microbiota were analyzed using 16S rRNA gene sequencing. We examined the impact of psychotropics (i.e., antidepressants, anxiolytics, antipsychotics) on their gut microbial diversity and functions. Results We collected 246 stool samples from 40 patients. Despite no differences in microbial diversity between medication groups at the baseline, over the course of treatment, phylogenic diversity whole-tree diversity decreased in patients on antipsychotics compared with patients without (P = .027), and beta diversity followed this trend. Based on a fixed-effect model, antipsychotics predicted microbial diversity; the higher doses correlated with less diversity based on the Shannon index and phylogenic diversity whole tree (estimate = −0.00254, SE = 0.000595, P < .0001; estimate = −0.02644, SE = 0.00833, P = .002, respectively). Conclusion Antipsychotics may play a role in decreasing the alpha diversity of the gut microbiome among patients with depression and anxiety, and our results indicate a relationship with medication dosage. Future studies are warranted and should consider patients’ types and doses of antipsychotics in order to further elucidate the mechanisms of gut-brain interactions in psychiatric disorders.


2021 ◽  
Vol 5 (1SP) ◽  
pp. 21
Author(s):  
Zakiudin Munasir

ABSTRACT Background: After birth, preterm infants face numerous challenges, including short and long-term morbidities, to survive and grow well with impaired immune and gastrointestinal systems. According to data from 184 countries, preterm birth rate ranges from 5-18%, accounting for 35% of all new born deaths. Purpose: This literature review aimed to summarize the evidence for the impact of prematurity on immune system development and the benefit of prebiotics on gut microbiota and immune responses. Discussion: Various studies in this narrative literature review showed that preterm infants have both qualitative and quantitative immune response deficits compared to term infants. Preterm newborns also have impaired intestinal immunity, underdeveloped intestinal mucosa barrier, and gut dysbiosis, which predisposes them to life-threatening infections. Early balanced gut microbiota in infants believed to be essential for adequate intestinal physiological functions and immune system maturation. The use of prebiotics, including human milk oligosaccharides (HMOs) in human breast milk, has been found to decrease the risk of various infections and cognitive impairment. A previous study found that prebiotic oligosaccharides supplementation was well-tolerated, significantly increased Bifidobacteria growth, and reduced the presence of gut pathogens. Conclusions: There was robust evidence that breast milk and prebiotics supplementation may support the gut microbiome and immune system in preterm infants. However, different types of synthetic prebiotics offer different benefits, and the protective effect seems to depend on the supplementation duration and dosage.


Author(s):  
Siti Rohaiza Ahmad

Maternal nutrition will not only affects pregnancy outcomes (such as birth weight) but will also affect the state of the fetus in their adult life in terms of diseases occurrence and also immune system development. Inadequate nutrition particularly will have a negative impact on the proliferation of the various cell populations responsible for the immune functions as well as the accumulation of high concentrations of inflammatory components. Maternal nutrition affects immunity ‘programming' during the period of pre-natal and post-natal life. Over the last decade, epidemiological and experimental studies have helped to expedite more understanding of immunity ‘programming.' External exposures such as smoking, alcohol and drugs during fetal life have also shown to have an impact on immunity ‘programming.' In this review, the relationship between fetal programming and the immune system, such as effects on the various immune-cellular components through some evidence from epidemiological and experimental models will be discussed.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1533-1533
Author(s):  
Wendy Cozen ◽  
Guoqin Yu ◽  
Mitchell Gail ◽  
Bharat N. Nathwani ◽  
Amie E. Hwang ◽  
...  

Abstract Abstract 1533 Survivors of adolescent/young adult Hodgkin lymphoma (AYAHL) report fewer exposures to infections during childhood compared to controls. They also have persistent genomic and functional aberrations in their lymphocytes that are partially attributable to chemotherapy or radiotherapy. Recent studies have shown that the gut microbiome can affect both the innate and adaptive immune response, and can suppress or exacerbate an inflammatory response. Given the central role of the gut microbiota in immune function, we investigated whether AYAHL survivors, who were members of 13 mono- and dizygotic twin pairs discordant for this disease, have differences in the diversity or phylogenetic configurations of their fecal microbiota compared to their unaffected co-twins. Twin pairs discordant for AYAHL are an ideal study population because they are at least partially matched on genetic and early life factors, both of which influence the composition of the gut microbiome. Pyrosequencing of bacterial 16S rRNA amplicons generated from single fecal samples obtained from each individual yielded 253,182 filtered and de-noised reads translated into species-level operational taxonomic units (OTUs). Standardized across individuals by random sampling, reads were assigned to 2513 OTUs to compare microbiome diversity and relative abundance of taxa. The number of OTU's was compared between twins using a paired student's t-test and a one-way analysis of variance was performed to determine whether such measures differed across twin pairs by comparing the measures between twins to those of randomly paired individuals. AYAHL survivors had less diverse fecal microbial communities compared to their unaffected co-twin controls by all measures of alpha diversity (Table 1). Measures that weighted the relative abundance of the bacteria were not statistically significantly different (Shannon Index, p= 0.270; Chao index, p= 0.066, PD Whole Tree Index, p= 0.051). However, when the unweighted number of unique OTUs was considered, the difference was significant (338 in cases vs. 369 in unaffected co-twin controls, p= 0.015). When the analysis was restricted to OTUs that were present at an abundance of > 0.1% in at least 2 of the 23 samples analyzed, the differences were attenuated, with only the PD Whole Tree index difference in diversity remaining marginally significant (p= 0.045). Only one bacterial taxon was associated with AYAHL, probably due to chance. Phylogenetic measurements indicated that the bacterial component of the microbiota of co-twins were more similar with respect to one another than unrelated individuals, although no differences by zygosity were observed. These results provide evidence that AYAHL survivors have reduced diversity of the gut microbiota, perhaps as a consequence the disease, its treatment, or a particularly hygienic environment. Table 1. Comparisons of alpha diversity measurements between Hodgkin lymphoma cases and co-twin controls. Measurements of Alpha Diversity Mean (Cases) Mean (Unaffected Co-twins) Mean Difference (Unaffected co-twin-case difference) P-value1 Initial analysis No. unique OTUs 338 369 31 0.015 Shannon index 5.6 5.8 0.2 0.27 Chao1 533 574 41 0.066 PD_whole tree 21.2 22.8 1.6 0.051 Conservative analysis No. unique OTUs 183 196 13 0.10 Shannon index 5.2 5.4 0.2 0.40 Chao1 230 237 7 0.47 PD_whole tree 13.7 14.6 0.9 0.045 1 P-value by paired t-tests. Disclosures: No relevant conflicts of interest to declare.


Life ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1329
Author(s):  
Diana Ćesić ◽  
Liborija Lugović-Mihić ◽  
Iva Ferček ◽  
Ana Gverić Grginić ◽  
Marko Jelić ◽  
...  

Background: Because of the important role in regulating the immune system, increasing evidence suggests a possible implication of gut microbiota in Chronic spontaneous urticaria (CSU). Although the oral cavity is the first site of contact between microbiota and the immune system, the association between salivary microbiota and CSU has not yet been reported. Objective: This case-control study aimed to compare differences in salivary microbiota between CSU patients and healthy controls (HC). Twenty-three participants—13 patients with CSU and 10 HC were enrolled; salivary microbiota was determined by molecular approach targeting 16S ribosomal RNA. Terminal restriction fragment length polymorphism (T-RFLP) analysis was performed. Results: Alpha diversity of salivary microbiota in CSU patients was significantly reduced compared to HC, resulting in alteration of the community composition. Species richness determined via the Shannon index was significantly reduced in the CSU group. Conclusion: Dysbiosis of salivary microbiota may contribute to a dysregulated immune system in the development of CSU. To our knowledge, this was the first study that reported an alteration in salivary microbiota composition in CSU patients.


Author(s):  
Xing Heng ◽  
Yuanhe Jiang ◽  
Weihua Chu

Antibiotics which can treat or prevent infectious diseases play an important role in medical therapy. However, the use of antibiotics has potential negative effects on the health of the host. For example, antibiotics use may affect the host's immune system by altering the gut microbiota. Therefore, the aim of the study was to investigate the influence of antifungal (fluconazole) treatment on gut microbiota and immune system of mice. Results showed that gut microbial composition of mice receiving fluconazole treatment was significantly changed after the trial. Fluconazole did not affect the relative abundance of bacteria but significantly reduced the diversity of bacterial flora. In the Bacteriome, Firmicutes and Proteobacteria significantly increased, while Bacteroidetes, Deferribacteres, Patescibacteria, and Tenericutes showed a remarkable reduction in fluconazole treated group in comparison with the control group. In the mycobiome, the relative abundance of Ascomycota was significantly decreased and Mucoromycota was significantly increased in the intestine of mice treated with fluconazole compared to the control group. RT-qPCR results showed that the relative gene expression of ZO-1, occludin, MyD88, IL-1β, and IL-6 was decreased in fluconazole-treated group compared to the control. Serum levels of IL-2, LZM and IgM were significantly increased, while IgG level had considerably down-regulated in the fluconazole-treated compared to the control. These results suggest that the administration of fluconazole can influence the gut microbiota and that a healthy gut microbiome is important for the regulation of the host immune responses.


2020 ◽  
Vol 21 (2) ◽  
pp. 503 ◽  
Author(s):  
Quanhang Xiang ◽  
Xiaoyu Wu ◽  
Ye Pan ◽  
Liu Wang ◽  
Chenbin Cui ◽  
...  

Previous studies have suggested that immune system development and weaning stress are closely related to the maturation of gut microbiota. The early-life period is a “window of opportunity” for microbial colonization, which potentially has a critical impact on the development of the immune system. Fecal microbiota transplantation (FMT) and probiotics are often used to regulate gut microbial colonization. This study aims to test whether early intervention with FMT using fecal microbiota from gestation sows combined with Clostridium butyricum and Saccharomyces boulardii (FMT-CS) administration could promote the maturation of gut microbiota and development of immune system in piglets. Piglets were assigned to control (n = 84) and FMT-CS treatment (n = 106), which were treated with placebo and bacterial suspension during the first three days after birth, respectively. By 16S rRNA gene sequencing, we found that FMT-CS increased the α-diversity and reduced the unweighted UniFrac distances of the OTU community. Besides, FMT-CS increased the relative abundance of beneficial bacteria, while decreasing that of opportunistic pathogens. FMT-CS also enhanced the relative abundance of genes related to cofactors and vitamin, energy, and amino acid metabolisms during the early-life period. ELISA analysis revealed that FMT-CS gave rise to the plasma concentrations of IL-23, IL-17, and IL-22, as well as the plasma levels of anti-M.hyo and anti-PCV2 antibodies. Furthermore, the FMT-CS-treated piglets showed decreases in inflammation levels and oxidative stress injury, and improvement of intestinal barrier function after weaning as well. Taken together, our results suggest that early-life intervention with FMT-CS could promote the development of innate and adaptive immune system and vaccine efficacy, and subsequently alleviate weaning stress through promoting the maturation of gut microbiota in piglets.


2020 ◽  
Vol 98 (11) ◽  
pp. 803-809 ◽  
Author(s):  
Yuanjiao Liang ◽  
Qi Ming ◽  
Jinlan Liang ◽  
Yan Zhang ◽  
Hong Zhang ◽  
...  

The objective was to explore if and how the microbiota changed in polycystic ovary syndrome (PCOS) women compared with healthy women. Eight obese PCOS (PO group), 10 nonobese PCOS (PN group), and nine healthy normal weight women (control) (C group) were enrolled. Insulin (INS), testosterone (T), follicle-stimulating hormone (FSH), luteinizing hormone (LH), estrogen (E2), and dehydroepiandrosterone (DHEA) were detected with radioimmunoassay. Antimullerian hormone (AMH), fasting glucose, and hemoglobin A1c (HbA1c) were determined by a chemiluminescence immunoassay, glucose oxidase method, and HPLC, respectively. Gut microbiota composition was evaluated by PCR. Alpha diversity was assessed using Chao1 and the Shannon index. PCOS women showed significantly higher T, LH, and LH/FSH and lower FSH levels than the C group (p < 0.05). The AMH level was significantly higher in the PO than in the PN group (p < 0.05). The PO group presented a significantly higher fasting INS level and HMOA-IR scores than the other groups, lower observed SVs and alpha diversity than the C group, higher beta diversity than the PN group (p < 0.05), and decreased abundances of genera (mainly butyrate producers). Regression analysis showed that decreased abundances of several genera were correlated with higher circulating T and impaired glucose metabolism. PCOS is associated with changes in the gut microbiota composition. Obesity has a driving role in the development of dysbiotic gut microbiota in PCOS.


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