Lactoferrin Ameliorates Dry Eye Disease Potentially through Enhancement of Short-Chain Fatty Acid Production by Gut Microbiota in Mice.
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ABSTRACT:
SUBMITTER: Connell S
PROVIDER: S-EPMC8624394 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:In recent years, short-chain fatty acids (SCFAs) have been reported to play an important role in maintaining human health. Fecal SCFA concentrations correlate well with colonic SCFA status and gut microbiota composition. However, the associations with the gut microbiota functional pathway, dietary intake, blood SCFAs, and fecal SCFAs remain uncertain. To clarify these relationships, we collected fecal samples, blood samples, and dietary habit data from 12 healthy adults aged 22-51 years. The relative abundance of several SCFA-producing bacteria, gut microbiota diversity, and functional pathways related to SCFA biosynthesis were positively associated with fecal SCFAs even after adjusting for age and sex. Furthermore, fecal acetate was likely to be positively associated with serum acetate. By contrast, dietary intake was not associated with fecal SCFAs. Overall, the present study highlights the potential usefulness of fecal SCFAs as an indicator of the gut microbiota ecosystem and dynamics of SCFAs in the human body.
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Project description:The graft-versus-host disease (GVHD) associated dry eye disease usually leads to refractory pain and visual impairment with limited treatments currently. Here we found exosome derived from mesenchymal stromal cell (MSC-exo) administered as eye drops significantly alleviates GVHD-associated dry eye disease in human and mouse models. To find out the essential elements during exosome treatment, we performed miRNA sequencing of exosomes derived from MSCs and L929 cells, and identified miR-204 in MSC-exo benefited the recovery of dry eye, which targeted IL-6/IL-6R/Stat3 signaling. Blockade of miR-204 abolished the therapeutic effect of MSC-exo while miR-204 overexpression from L929-exo markedly attenuates dry eye. Thus MSC-exo eye drops are efficacious in treating GVHD-associated dry eye and highlight miR-204 as a potential therapeutic agent.
2022-01-19 | GSE166585 | GEO
Project description:The goal of this study is to compare transcriptome profiling of n-butyrate treated immortalized human endometriotic epithelial cells expression Luciferase (iHEECs/Luc) by RNA-sequencing Methods: The mRNA profiles of vehicle and n-butyrate treated immortalized human endometriotic epithelial cells expression Luciferase (iHEECs/Luc) were generated by deep sequencing, in triplicate using Illumina NovaSeq-6000 sequencers with 2×150 paired-end reads. Basecalls and demultiplexing were performed with Illumina’s RTA version 1.9 and bcl2fastq2 software with a maximum of one mismatch in the indexing read. RNA-seq reads were then aligned to the Ensembl release 76 primary assembly with STAR version 2.5.1a. qRT–PCR validation was performed using TaqMan assays. Results: Using a 2.5-fold cutoff and Benjamini-Hochberg false discovery rate (FDR) of <0.01 threshold for inclusion, we identified 1,830 differentially expressed genes (DEGs) between Vehicle and n-butyrate treated immortalized human endometriotic epithelial cells expression Luciferase (iHEECs/Luc). Conclusions: Our study represents the first detailed analysis of n-butyrate treated immortalized human endometriotic epithelial cells expression Luciferase (iHEECs/Luc) transcriptomes, with biologic replicates, generated by RNA-seq technology.
2021-09-29 | GSE184431 | GEO
Project description:We recently hypothesized that the intestinal microbiota and the innate immune system play key roles in the mechanism of Kilham Rat Virus-induced type 1 diabetes in the LEW1.WR1 rat. We used this animal model to test the hypothesis that maternal therapy with short-chain fatty acids can modulate the intestinal microbiota and reverse virus-induced proinflammatory responses and type 1 diabetes in rat offspring. We observed that administration of short-chain fatty acids to rat breeders via drinking water prior to pregnancy and further treatment of the offspring with short-chain fatty acids after weaning led to disease amelioration. In contrast, rats that were administered short-chain fatty acids beginning at weaning were not protected from type 1 diabetes. Short-chain fatty acid therapy exerted a profound effect on the intestinal microbiome in the offspring reflected by a reduction and an increase in the abundances of Firmicutes and Bacteroidetes taxa, respectively, on day 5 post-infection, and reversed virus-induced alterations in certain bacterial taxa. Principal component analysis and permutation multivariate analysis of variance tests further revealed that short-chain fatty acids induce a distinct intestinal microbiota compared with uninfected animals or rats that receive the virus only. Short-chain fatty acids downregulated Kilham Rat Virus-induced proinflammatory responses in the intestine. Finally, short-chain fatty acids altered the B and T cell compartments in Peyer's patches. These data demonstrate that short-chain fatty acids can reshape the intestinal microbiota and prevent virus-induced islet autoimmunity and may therefore represent a useful therapeutic strategy for disease prevention.
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Project description:Gut dysbiosis has been repeatedly reported in Parkinson's disease (PD) but only once in idiopathic rapid-eye-movement sleep behavior disorder (iRBD) from Germany. Abnormal aggregation of ?-synuclein fibrils causing PD possibly starts from the intestine, although this is still currently under debate. iRBD patients frequently develop PD. Early-stage gut dysbiosis that is causally associated with PD is thus expected to be observed in iRBD. We analyzed gut microbiota in 26 iRBD patients and 137 controls by 16S rRNA sequencing (16S rRNA-seq). Our iRBD data set was meta-analyzed with the German iRBD data set and was compared with gut microbiota in 223 PD patients. Unsupervised clustering of gut microbiota by LIGER, a topic model-based tool for single-cell RNA sequencing (RNA-seq) analysis, revealed four enterotypes in controls, iRBD, and PD. Short-chain fatty acid (SCFA)-producing bacteria were conserved in an enterotype observed in controls and iRBD, whereas they were less conserved in enterotypes observed in PD. Genus Akkermansia and family Akkermansiaceae were consistently increased in both iRBD in two countries and PD in five countries. Short-chain fatty acid (SCFA)-producing bacteria were not significantly decreased in iRBD in two countries. In contrast, we previously reported that recognized or putative SCFA-producing genera Faecalibacterium, Roseburia, and Lachnospiraceae ND3007 group were consistently decreased in PD in five countries. In ?-synucleinopathy, increase of mucin-layer-degrading genus Akkermansia is observed at the stage of iRBD, whereas decrease of SCFA-producing genera becomes obvious with development of PD.IMPORTANCE Twenty studies on gut microbiota in PD have been reported, whereas only one study has been reported on iRBD from Germany. iRBD has the highest likelihood ratio to develop PD. Our meta-analysis of iRBD in Japan and Germany revealed increased mucin-layer-degrading genus Akkermansia in iRBD. Genus Akkermansia may increase the intestinal permeability, as we previously observed in PD patients, and may make the intestinal neural plexus exposed to oxidative stress, which can lead to abnormal aggregation of prion-like ?-synuclein fibrils in the intestine. In contrast to PD, SCFA-producing bacteria were not decreased in iRBD. As SCFA induces regulatory T (Treg) cells, a decrease of SCFA-producing bacteria may be a prerequisite for the development of PD. We propose that prebiotic and/or probiotic therapeutic strategies to increase the intestinal mucin layer and to increase intestinal SCFA potentially retard the development of iRBD and PD.
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Project description:A growing body of evidence highlights the relevance of free fatty acids (FFA) for human health, and their role in the cross talk between the metabolic status and immune system. Altered serum FFA profiles are related to several metabolic conditions, although the underlying mechanisms remain unclear. Recent studies have highlighted the link between gut microbiota and host metabolism. However, although most of the studies have focused on different clinical conditions, evidence on the role of these mediators in healthy populations is lacking. Therefore, we have addressed the analysis of the relationship among gut microbial populations, short-chain fatty acid (SCFA) production, FFA levels, and immune mediators (IFNγ, IL-6, and MCP-1) in 101 human adults from the general Spanish population. Levels of selected microbial groups, representing the major phylogenetic types present in the human intestinal microbiota, were determined by quantitative PCR. Our results showed that the intestinal abundance of Akkermansia was the main predictor of total FFA serum levels, displaying a negative association with total FFA and the pro-inflammatory cytokine IL-6. Similarly, an altered FFA profile, identified by cluster analysis, was related to imbalanced levels of Akkermansia and Lactobacillus as well as increased fecal SCFA, enhanced IL-6 serum levels, and higher prevalence of subclinical metabolic alterations. Although no differences in nutritional intakes were observed, divergent patterns in the associations between nutrient intakes with intestinal microbial populations and SCFA were denoted. Overall, these findings provide new insights on the gut microbiota-host lipid metabolism axis and its potential relevance for human health, where FFA and SCFA seem to play an important role.
| S-EPMC5522850 | biostudies-other
Project description:Intestinal microbiota seems to play a key role in obesity. The impact of the composition and/or functionality of the obesity-associated microbiota have yet to be fully characterized. This work assessed the significance of the taxonomic composition and/or metabolic activity of obese- microbiota by massive 16S rRNA gene sequencing of the fecal microbiome of obese and normoweight individuals. The obese metabolic activity was also assessed by in vitro incubation of obese and normoweight microbiotas in nutritive mediums with different energy content. We found that the microbiome richness and diversity of the two groups did not differ significantly, except for Chao1 index, significantly higher in normoweight individuals. At phylum level, neither the abundance of Firmicutes or Bacteroidetes nor their ratio was associated with the body mass index. Besides, the relative proportions in Collinsella, Clostridium XIVa, and Catenibacterium were significantly enriched in obese participants, while Alistipes, Clostridium sensu stricto, Romboutsia, and Oscillibacter were significantly diminished. In regard to metabolic activity, short-chain fatty acids content was significant higher in obese individuals, with acetate being the most abundant followed by propionate and butyrate. Acetate and butyrate production was also higher when incubating obese microbiota in mediums mimicking diets with different energy content; interestingly, a reduced capability of propionate production was associated to the obese microbiome. In spite of the large interindividual variability, the obese phenotype seems to be defined more by the abundance and/or the absence of distinct communities of microorganism rather than by the presence of a specific population.
| S-EPMC8242951 | biostudies-literature
Project description:BackgroundCancer cachexia is characterized by a negative energy balance, muscle and adipose tissue wasting, insulin resistance, and systemic inflammation. Because of its strong negative impact on prognosis and its multifactorial nature that is still not fully understood, cachexia remains an important challenge in the field of cancer treatment. Recent animal studies indicate that the gut microbiota is involved in the pathogenesis and manifestation of cancer cachexia, but human data are lacking. The present study investigates gut microbiota composition, short-chain fatty acids (SCFA), and inflammatory parameters in human cancer cachexia.MethodsFaecal samples were prospectively collected in patients (N = 107) with pancreatic cancer, lung cancer, breast cancer, or ovarian cancer. Household partners (N = 76) of the patients were included as healthy controls with similar diet and environmental conditions. Patients were classified as cachectic if they lost >5% body weight in the last 6 months. Gut microbiota composition was analysed by sequencing of the 16S rRNA V4 gene region. Faecal SCFA levels were quantified by gas chromatography. Faecal calprotectin was assessed with enzyme-linked immunosorbent assay. Serum C-reactive protein and leucocyte counts were retrieved from medical records.ResultsCachexia prevalence was highest in pancreatic cancer (66.7%), followed by ovarian cancer (25%), lung cancer (20.8%), and breast cancer (17.3%). Microbial α-diversity was not significantly different between cachectic cancer patients (N = 33), non-cachectic cancer patients (N = 74), or healthy controls (N = 76) (species richness P = 0.31; Shannon effective index P = 0.46). Community structure (β-diversity) tended to differ between these groups (P = 0.053), although overall differences were subtle and no clear clustering of samples was observed. Proteobacteria (P < 0.001), an unknown genus from the Enterobacteriaceae family (P < 0.01), and Veillonella (P < 0.001) were more abundant among cachectic cancer patients. Megamonas (P < 0.05) and Peptococcus (P < 0.001) also showed differential abundance. Faecal levels of all SCFA tended to be lower in cachectic cancer patients, but only acetate concentrations were significantly reduced (P < 0.05). Faecal calprotectin levels were positively correlated with the abundance of Peptococcus, unknown Enterobacteriaceae, and Veillonella. We also identified several correlations and interactions between clinical and microbial parameters.ConclusionsThis clinical study provided the first insights into the alterations of gut microbiota composition and SCFA levels that occur in cachectic cancer patients and how they are related to inflammatory parameters. These results pave the way for further research examining the role of the gut microbiota in cancer cachexia and its potential use as therapeutic target.
| S-EPMC8718054 | biostudies-literature
Project description:Many studies have focused on the metabolic capacity of human gut microbiota to produce short-chain fatty acids and subsequent effects on host physiology. Given scarce data on how SCFAs produced by gut bacteria participate in cross-feeding to influence community structure and function, we evaluated the potential of SCFAs to modulate human gut microbiota in vitro. We employed anaerobic fecal cultivation in chemically defined medium supplemented with one of nine SCFAs to determine effects on both gut microbial community structure via 16S rRNA sequencing and function via genome reconstruction analysis. Each SCFA displayed significant and unique modulatory potential with respect to the relative abundance of bacterial taxa. Analysis of SCFA-supplemented communities revealed that alterations of individual closely related phylotypes displayed coherent changes, although exceptions were also observed which suggest strain-dependent differences in SCFA-induced changes. We used genome reconstruction to evaluate the functional implications of SCFA-mediated restructuring of fecal communities. We note that some SCFA-supplemented cultures displayed a reduction in the predicted abundance of SCFA producers, which suggests a possible undefined negative feedback mechanism. We conclude that SCFAs are not simply end-products of metabolism but also serve to modulate the gut microbiota through cross-feeding that alters the fitness of specified taxa. These results are important in the identification of prebiotics that elevate specific SCFAs for therapeutic benefit and highlight SCFA consumers as a salient part of the overall metabolic flux pertaining to bacterial fermentative processes.
| S-EPMC8921067 | biostudies-literature
Project description:PurposeTo investigate accommodative microfluctuations (AMFs) and visual function in short tear break-up time (BUT)-type dry eye (DE) and non-DE subjects.MethodsThis prospective comparative study included 48 volunteers with DE symptoms (mean age 34.8 ± 5.5 years, age range 25-42 years) and 73 without DE symptoms (mean age 30.6 ± 4.7 years, age range 25-42 years). The eyes were divided into two groups: (1) DE group with DE symptoms and BUT ≤ 5 s and (2) non-DE group without DE symptoms and BUT > 5 s. We excluded eyes with Schirmer score ≤ 5 mm and positive keratoconjunctival epithelial damage. Tear evaluation, AMF, and functional visual acuity (VA) examinations were performed. AMF parameters included total high-frequency component (HFC), HFC with low accommodation for the task of staring into the distance (HFC1), and HFC with high accommodation for deskwork (HFC2). Functional VA parameters included starting VA, functional VA, visual maintenance ratio, and blink frequency.ResultsA total of 33 and 34 eyes were categorized in the DE and non-DE groups, respectively. Mean blink frequency and HFC1 values were significantly higher in the DE group than they were in the non-DE group.ConclusionsDEs with symptoms showed abnormal AMF and visual function, which may be associated with DE symptoms.
| S-EPMC5590915 | biostudies-literature