scholarly journals Encapsulated cyclosporine does not change the composition of the human microbiota when assessed ex vivo and in vivo

2020 ◽  
Vol 69 (6) ◽  
pp. 854-863
Author(s):  
Catherine O'Reilly ◽  
Órla O’Sullivan ◽  
Paul D. Cotter ◽  
Paula M. O’Connor ◽  
Fergus Shanahan ◽  
...  

Introduction. Management of steroid-refractory ulcerative colitis has predominantly involved treatment with systemic cyclosporine A (CyA) and infliximab. Aim. The purpose of this study was to assess the effect of using a colon-targeted delivery system CyA formulation on the composition and functionality of the gut microbiota. Methodology. Ex vivo faecal fermentations from six healthy control subjects were treated with coated minispheres (SmPill) with (+) or without (−) CyA and compared with a non-treated control in a model colon system. In addition, the in vivo effect of the SmPill+CyA formulation was investigated by analysing the gut microbiota in faecal samples collected before the administration of SmPill+CyA and after 7 consecutive days of administration from eight healthy subjects who participated in a pilot study. Results. Analysis of faecal samples by 16S rRNA gene sequencing indicated little variation in the diversity or relative abundance of the microbiota composition before or after treatment with SmPill minispheres with or without CyA ex vivo or with CyA in vivo. Short-chain fatty acid profiles were evaluated using gas chromatography, showing an increase in the concentration of n-butyrate (P=0.02) and acetate (P=0.32) in the faecal fermented samples incubated in the presence of SmPill minispheres with or without CyA. This indicated that increased acetate and butyrate production was attributed to a component of the coated minispheres rather than an effect of CyA on the microbiota. Butyrate and acetate levels also increased significantly (P=0.05 for both) in the faecal samples of healthy individuals following 7 days’ treatment with SmPill+CyA in the pilot study. Conclusion. SmPill minispheres with or without CyA at the clinically relevant doses tested here have negligible direct effects on the gut microbiota composition. Butyrate and acetate production increased, however, in the presence of the beads in an ex vivo model system as well as in vivo in healthy subjects. Importantly, this study also demonstrates the relevance and value of using ex vivo colon models to predict the in vivo impact of colon-targeted drugs directly on the gut microbiota.

2019 ◽  
Author(s):  
Sejal Morjaria ◽  
Allen W. Zhang ◽  
Sohn Kim ◽  
Jonathan U. Peled ◽  
Simone Becattini ◽  
...  

BackgroundMonocytes are an essential cellular component of the innate immune system that support the host’s effectivenss to combat a range of infectious pathogens. Hemopoietic cell transplantation (HCT) results in transient monocyte depletion, but the factors that regulate recovery of monocyte populations are not fully understood. In this study, we investigated whether the composition of the gastrointestinal microbiota is associated with the recovery of monocyte homeostasis after HCT.MethodsWe performed a single-center, prospective, pilot study of 18 recipients of either autologous or allogeneic HCT. Serial blood and stool samples were collected from each patient during their HCT hospitalization. Analysis of the gut microbiota was done using 16S rRNA gene sequencing and flow cytometric analysis was used to characterize the phenotypic composition of monocyte populations.ResultsDynamic fluctuations in monocyte reconstitution occurred after HCT and large differences were observed in monocyte frequency among patients over time. Recovery of absolute monocyte counts and monocyte subsets showed significant variability across the heterogeneous transplant types and conditioning intensities; no relationship to the microbiota composition was observed in this small cohort.ConclusionA relationship between the microbiota composition and monocyte homeostasis could not be firmly established in this pilot study.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chunyan Su ◽  
Xingxing Li ◽  
Yuxin Yang ◽  
Yu Du ◽  
Xiumin Zhang ◽  
...  

AbstractTrimethylamine-N-oxide (TMAO), a gut-microbiota-dependent metabolite generated from its dietary precursors such as choline, has been identified as an independent risk factor for atherosclerosis. Metformin is the most widely used drug for the treatment of type 2 diabetes (T2D), which has therapeutic effects on hyperglycemia accelerated atherosclerosis. A growing body of evidence suggest that metformin plays a therapeutic role by regulating the structure and metabolic function of gut microbiota. However, whether metformin has an impact on gut-microbiota-mediated TMAO production from choline remains obscure. In this study, the oral administration of metformin significantly reduced choline diet-increased serum TMAO in choline diet-fed C57BL/6J mice. The diversity analysis based on 16S rRNA gene sequencing of C57BL/6J mice fecal samples indicated that metformin markedly changed the gut-microbiota composition. Metformin was positively correlated with the enrichment of different intestinal bacteria such as Bifidobacterium and Akkermansia and a lower cutC (a choline utilization gene) abundance. Furthermore, the ex vivo and in vitro inhibitory effects of metformin on choline metabolism of TMA-producing bacteria were confirmed under anaerobic condition. The results suggested that metformin suppresses serum TMAO level by remodeling gut microbiota involved in TMA generation from choline.


2020 ◽  
Author(s):  
Katarina Butorac ◽  
Martina Banic ◽  
Jasna Novak ◽  
Andreja Leboš Pavunc ◽  
Ksenija Uroic ◽  
...  

Abstract Background: The influence of an S-layer-carrying strain Lactobacillus brevis SF9B and a plantaricin-producing strain Lactobacillus plantarum SF9C on the gut microbiota composition was evaluated in the rats. Considering the probiotic potential of Lb. brevis SF9B, this study aimed to examine the antibacterial activity of Lb. plantarum SF9C and potential for their in vivo colonisation, which could be the basis for the investigation of their synergistic functionality. Results: A plantaricin-encoding cluster was identified in Lb. plantarum SF9C, a strain which efficiently inhibited the growth of Listeria monocytogenes ATCC®19111™ and Staphylococcus aureus 3048. Contrary to the plantaricin-producing SF9C strain, the S-layer-carrying SF9B strain excluded Escherichia coli 3014 and Salmonella enterica serovar Typhimurium FP1 from adhesion to Caco-2 cells. Finally, DGGE analysis of the V2-V3 region of the 16S rRNA gene confirmed the transit of two selected lactobacilli through the gastrointestinal tract (GIT). Microbiome profiling via the Illumina MiSeq platform revealed the prevalence of Lactobacillus spp. in the gut microbiota of rats suggesting their colonisation potential in GIT.Conclusion: The combined application of Lb. plantarum SF9C and Lb. brevis SF9B could influence the intestinal microbiota composition, which is reflected through the increased abundance of Lactobacillus genus, but also through altered abundances of other bacterial genera, either in the model of healthy or aberrant microbiota of rats. The obtained results contributed to the functional aspects of SF9C and SF9B strains which could be incorporated in the probiotic-containing functional foods and therefore have a beneficial influence on the gut microbiota composition.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Jason R. Catanzaro ◽  
Juliet D. Strauss ◽  
Agata Bielecka ◽  
Anthony F. Porto ◽  
Francis M. Lobo ◽  
...  

Abstract Immunoglobulin A is the dominant antibody isotype found in mucosal secretions and enforces host-microbiota symbiosis in mice, yet selective IgA-deficiency (sIgAd) in humans is often described as asymptomatic. Here, we determined the effects of IgA deficiency on human gut microbiota composition and evaluated the possibility that mucosal secretion of IgM can compensate for a lack of secretory IgA. We used 16S rRNA gene sequencing and bacterial cell sorting to evaluate gut microbiota composition and taxa-specific antibody coating of the gut microbiota in 15 sIgAd subjects and matched controls. Despite the secretion of compensatory IgM into the gut lumen, sIgAd subjects displayed an altered gut microbiota composition as compared to healthy controls. These alterations were characterized by a trend towards decreased overall microbial diversity as well as significant shifts in the relative abundances of specific microbial taxa. While secretory IgA in healthy controls targeted a defined subset of the microbiota via high-level coating, compensatory IgM in sIgAd subjects showed less specificity than IgA and bound a broader subset of the microbiota. We conclude that IgA plays a critical and non-redundant role in controlling gut microbiota composition in humans and that secretory IgA has evolved to maintain a diverse and stable gut microbial community.


Author(s):  
Alinne P. Castro ◽  
Keemilyn K. S. Silva ◽  
Claudia S. A. Medeiros ◽  
Fernanda Alves ◽  
Ronaldo C. Araujo ◽  
...  

In addition to its health benefits, exercise training has been pointed out as modulator of the gut microbiota. However, the effects of resistance training (RT) on gut microbiota composition remain unknown. Wistar rats underwent 12 weeks of RT. Body weight, glucose tolerance test, visceral body fat, triglyceride concentration, and food consumption were evaluated. The gut microbiota was analyzed by 16S rRNA gene sequencing. Rats that underwent RT showed lower body weight (p=0.0005), lower fat content (p=0.02), and better glucose kinetics (p=0.047) when compared to the control. Improvements in the diversity and composition of the gut microbiota were identified in the RT group. The relative abundance of Pseudomonas, Serratia, and Comamonas decreased significantly after 12 weeks of RT (p<0.001). These results suggest that RT has the potential to enhance the diversity of the gut microbiota and improve its biological functions.


2021 ◽  
Author(s):  
Yin-Ping Guo ◽  
Li Shao ◽  
Li Wang ◽  
Man-Yun Chen ◽  
Wei Zhang ◽  
...  

Abstract Background: Ginsenoside CK (GCK) serves as the potential anti-colorectal cancer (CRC) protopanaxadiol (PPD)-type saponin, which could be mainly bio-converted to yield PPD by gut microbiota. Meanwhile, the anti-CRC effects of GCK could be altered by gut microbiota due to its different diversity in CRC patients. We aimed to investigate the bioconversion variation of GCK mediated by gut microbiota from CRC patients by comparing with healthy subjects.Methods: Gut microbiota profiled by 16S rRNA gene sequencing was collected from healthy volunteers and CRC patients. GCK was incubated with gut microbiota in vitro. A LC-MS/MS method was validated to quantify GCK and PPD after incubation at different time points.Results: The bioconversion of GCK in healthy subjects group was much faster than CRC group, as well as the yield of PPD. Moreover, significant difference of PPD concentration between healthy subjects group and CRC group could be observed at 12 h, 48 h and 72 h check points. According to 16S rRNA sequencing, the profiles of gut microbiota derived from healthy volunteers and CRC patients significantly varied, in which 12 differentially abundant taxon were found, such as Bifidobacterium, Roseburia, Bacteroides and Collinsella. Spearman’s correlation analysis showed bacteria enriched in healthy subjects group were positively associated with biotransformation of GCK, while bacteria enriched in CRC group displayed non correlation characters. Among them, Roseburia which could secrete β-glycosidase showed the strongest positive association with the bioconversion of GCK.Conclusion: The bioconversion of GCK in healthy subjects was much faster than CRC patients mediated by gut microbiota, which might alter the anti-CRC effects of GCK.


Author(s):  
Ayorinde O. Afolayan ◽  
Elena Biagi ◽  
Simone Rampelli ◽  
Marco Candela ◽  
Patrizia Brigidi ◽  
...  

Despite well-established knowledge of the role of diet and the geographic effect on the gut microbiota of human populations, the temporal dynamics of the individual microbiota profile across changes associated with intercontinental short residence are still far from being understood. This pilot study sought to provide insights into the trajectory of the gut microbiota of an individual during a two-month stay in Italy and a subsequent two-month stay in Nigeria, by 16S rRNA gene sequencing and inferred metagenomics. The gut microbiota underwent massive but temporary changes, both taxonomically and based on predicted functionality. The faecal microbiota associated with the short stay in Italy progressively lost diversity and showed a dominance of Firmicutes, while after returning to Nigeria, the microbial community quickly regained the typical profile, in terms of biodiversity and bacterial signatures of traditional lifestyle, i.e., Prevotella and Treponema. Predicted pathways involved in glycolysis, fermentation and N-acetylneuraminate degradation were enriched during the subsequent two-month stay in Nigeria, whereas pathways associated with amino acid and peptidoglycan synthesis and maturation became over-represented during short stay in Italy. Our findings stress the plasticity of the individual gut microbiota even during a short-term travel, with loss/gain of taxonomic and functional features that mirror those of the gut microbiota of indigenous people dwelling therein.


2021 ◽  
Vol 11 (12) ◽  
pp. 1381
Author(s):  
Han-Na Kim ◽  
Jae-Heon Kim ◽  
Yoosoo Chang ◽  
Dongmin Yang ◽  
Hyung-Lae Kim ◽  
...  

Animal studies have shown the interaction between androgens and the gut microbiome directly and indirectly; however, limited evidence from human studies is available. To evaluate the association between prostate-specific antigen (PSA) levels within the normal range, reflective of androgen receptor activity, and the gut microbiota composition, a cross-sectional analysis was performed in 759 Korean men aged between 25 and 78 years with normal PSA levels of ≤4.0 ng/mL. We evaluated the biodiversity of gut microbiota as well as the taxonomic and functional signatures associated with PSA levels using 16S rRNA gene sequencing data. PSA levels within the normal range were categorized into three groups: lowest quartile (G1), interquartile range (G2, reference), and highest quartile (G3). The G3 group had higher microbial richness than the G2 group, although it was dominated by a few bacteria. An increase in Escherichia/Shigella abundance and a reduction in Megamonas abundance in the G3 group were also detected. A U-shaped relationship was observed between the three groups across most analyses, including biodiversity, taxonomic composition, and inferred pathways in the gut microbiota. This study showed different microbiota patterns across PSA levels within the normal range. Further studies are required to elucidate the role of microbiota in regulating PSA levels.


Author(s):  
F. Borgo ◽  
A. D. Macandog ◽  
S. Diviccaro ◽  
E. Falvo ◽  
S. Giatti ◽  
...  

Abstract Purpose Post-finasteride syndrome (PFS) has been reported in a subset of patients treated with finasteride (an inhibitor of the enzyme 5alpha-reductase) for androgenetic alopecia. These patients showed, despite the suspension of the treatment, a variety of persistent symptoms, like sexual dysfunction and cognitive and psychological disorders, including depression. A growing body of literature highlights the relevance of the gut microbiota-brain axis in human health and disease. For instance, alterations in gut microbiota composition have been reported in patients with major depressive disorder. Therefore, we have here analyzed the gut microbiota composition in PFS patients in comparison with a healthy cohort. Methods Fecal microbiota of 23 PFS patients was analyzed by 16S rRNA gene sequencing and compared with that reported in ten healthy male subjects. Results Sexual dysfunction, psychological and cognitive complaints, muscular problems, and physical alterations symptoms were reported in more than half of the PFS patients at the moment of sample collection. The quality sequence check revealed a low library depth for two fecal samples. Therefore, the gut microbiota analyses were conducted on 21 patients. The α-diversity was significantly lower in PFS group, showing a reduction of richness and diversity of gut microbiota structure. Moreover, when visualizing β-diversity, a clustering effect was found in the gut microbiota of a subset of PFS subjects, which was also characterized by a reduction in Faecalibacterium spp. and Ruminococcaceae UCG-005, while Alloprevotella and Odoribacter spp were increased compared to healthy control. Conclusion Gut microbiota population is altered in PFS patients, suggesting that it might represent a diagnostic marker and a possible therapeutic target for this syndrome.


2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S650-S651
Author(s):  
S Cocciolillo ◽  
G De Palma ◽  
T Chen ◽  
M P Ghali ◽  
M Deschenes ◽  
...  

Abstract Background Non-alcoholic fatty liver disease (NAFLD) is the main cause of liver disease in Western countries and is a frequently reported comorbidity in inflammatory bowel disease (IBD). A complex interaction among polygenic predisposition, IBD-specific risk factors, microbiome, multiple environmental and patients’ factors could explain the development of NAFLD in IBD. Gut dysbiosis is increasingly recognised as an important player in NAFLD, as well as in IBD pathogenesis. So far, no study has examined the gut microbiota composition in IBD patients with NAFLD. We aimed to characterise faecal microbiota according to NAFLD status in a pilot cohort of ulcerative colitis (UC) pancolitis in clinical remission. Methods This was a cross-sectional pilot study using transient elastography (TE) with controlled attenuation parameter (CAP) to diagnose NAFLD in UC pancolitis patients in clinical remission, defined as partial Mayo score ≤1. NAFLD was diagnosed non-invasively as CAP ≥248 dB/m. Exclusion criteria included: use of corticosteroids in the last year and antibiotics or probiotics/prebiotics in the last 2 months prior to inclusion; significant alcohol intake (AUDIT-C <5); hepatitis B or C infection. Stool samples were collected within 12 h from TE with CAP evaluation. Gut microbiota composition was analysed by 16S rRNA gene sequencing with Illumina technique. Statistical analysis by NAFLD status was performed using Fisher’s exact or Mann–Whitney’s test as appropriate. Results A total of 11 UC pancolitis patients in clinical remission were included (mean age 53 years, 36.4% male, time since IBD diagnosis 16 years). NAFLD was diagnosed in 7 cases (63.6%, mean CAP 291 dB/m). Patients with pancolitis and NAFLD had higher BMI (mean 31 vs. 22 kg/m2, p = 0.006) as well as waist circumference (mean 100 vs. 81 cm, p = 0.006) compared with those without NAFLD, but no other differences in demographic, clinical or pharmacological parameters were found between pancolitis with or without NAFLD. Patients with pancolitis and NAFLD clustered separately from those without NAFLD, when computing Bray Curtis dissimilarities (tested with Adonis, p = 0.006). In addition, patients with pancolitis and NAFLD presented with decreased bacterial richness (p = 0.017) but not diversity. This was accompanied by a significant increase of Bacteroides spp. relative abundance in faecal samples of patients with pancolitis and NAFLD (q = 0.017). Conclusion This pilot study demonstrates, for the first time, that, in UC pancolitis patients, NAFLD associates with altered gut microbiota composition. Further studies are needed to understand the exact role of gut microbiota in UC pancolitis with NAFLD and to evaluate the use of microbiota-directed approaches for the treatment of NAFLD in these patients.


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