scholarly journals The Mammalian Intestinal Microbiome: Composition, Interaction with the Immune System, Significance for Vaccine Efficacy, and Potential for Disease Therapy

Pathogens ◽  
2018 ◽  
Vol 7 (3) ◽  
pp. 57 ◽  
Author(s):  
Ulrich Desselberger

The mammalian gut is colonized by a large variety of microbes, collectively termed ‘the microbiome’. The gut microbiome undergoes rapid changes during the first few years of life and is highly variable in adulthood depending on various factors. With the gut being the largest organ of immune responses, the composition of the microbiome of the gut has been found to be correlated with qualitative and quantitative differences of mucosal and systemic immune responses. Animal models have been very useful to unravel the relationship between gut microbiome and immune responses and for the understanding of variations of immune responses to vaccination in different childhood populations. However, the molecular mechanisms underlying optimal immune responses to infection or vaccination are not fully understood. The gut virome and gut bacteria can interact, with bacteria facilitating viral infectivity by different mechanisms. Some gut bacteria, which have a beneficial effect on increasing immune responses or by overgrowing intestinal pathogens, are considered to act as probiotics and can be used for therapeutic purposes (as in the case of fecal microbiome transplantation).

Nutrients ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 1630 ◽  
Author(s):  
Daphne M. Rodriguez ◽  
Abby D. Benninghoff ◽  
Niklas D.J. Aardema ◽  
Sumira Phatak ◽  
Korry J. Hintze

The Western dietary pattern can alter the gut microbiome and cause obesity and metabolic disorders. To examine the interactions between diet, the microbiome, and obesity, we transplanted gut microbiota from lean or obese human donors into mice fed one of three diets for 22 weeks: (1) a control AIN93G diet; (2) the total Western diet (TWD), which mimics the American diet; or (3) a 45% high-fat diet-induced obesity (DIO) diet. We hypothesized that a fecal microbiome transfer (FMT) from obese donors would lead to an obese phenotype and aberrant glucose metabolism in recipient mice that would be exacerbated by consumption of the TWD or DIO diets. Prior to the FMT, the native microbiome was depleted using an established broad-spectrum antibiotic protocol. Interestingly, the human donor body type microbiome did not significantly affect final body weight or body composition in mice fed any of the experimental diets. Beta diversity analysis and linear discriminant analysis with effect size (LEfSe) showed that mice that received an FMT from obese donors had a significantly different microbiome compared to mice that received an FMT from lean donors. However, after 22 weeks, diet influenced the microbiome composition irrespective of donor body type, suggesting that diet is a key variable in the shaping of the gut microbiome after FMT.


Nutrients ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1874 ◽  
Author(s):  
Angela Horvath ◽  
Marija Durdevic ◽  
Bettina Leber ◽  
Katharina di Vora ◽  
Florian Rainer ◽  
...  

Probiotics have been used in trials to therapeutically modulate the gut microbiome and have shown beneficial effects in cirrhosis. However, their effect on the microbiome of cirrhosis patients is not fully understood yet. Here, we tested the effects of a multispecies probiotic on microbiome composition in compensated cirrhosis. The gut microbiome composition of 58 patients with compensated cirrhosis from a randomized controlled trial who received a daily dose of multispecies probiotics or placebo for six months was analysed by 16S rRNA gene sequencing. Microbiome composition of patients who received probiotics was enriched with probiotic strains and the abundance of Faecalibacterium prausnitzii, Syntrophococcus sucromutans, Bacteroides vulgatus, Alistipes shahii and a Prevotella species was increased in the probiotic group compared to the placebo group. Patients who had microbiome changes in response to probiotic treatment also showed a significant increase in neopterin and a significant decrease in faecal zonulin levels after intervention, which was not observed in placebo-treated patients or patients with unchanged microbiome compositions. In conclusion, multispecies probiotics may enrich the microbiome of compensated cirrhotic patients with probiotic bacteria during a six-month intervention and beneficially change the residential microbiome and gut barrier function.


2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Cindy G. Boer ◽  
Djawad Radjabzadeh ◽  
Carolina Medina-Gomez ◽  
Sanzhima Garmaeva ◽  
Dieuwke Schiphof ◽  
...  

Abstract Macrophage-mediated inflammation is thought to have a causal role in osteoarthritis-related pain and severity, and has been suggested to be triggered by endotoxins produced by the gastrointestinal microbiome. Here we investigate the relationship between joint pain and the gastrointestinal microbiome composition, and osteoarthritis-related knee pain in the Rotterdam Study; a large population based cohort study. We show that abundance of Streptococcus species is associated with increased knee pain, which we validate by absolute quantification of Streptococcus species. In addition, we replicate these results in 867 Caucasian adults of the Lifelines-DEEP study. Finally we show evidence that this association is driven by local inflammation in the knee joint. Our results indicate the microbiome is a possible therapeutic target for osteoarthritis-related knee pain.


mSphere ◽  
2017 ◽  
Vol 2 (6) ◽  
Author(s):  
Steven A. Frese ◽  
Andra A. Hutton ◽  
Lindsey N. Contreras ◽  
Claire A. Shaw ◽  
Michelle C. Palumbo ◽  
...  

ABSTRACT The gut microbiome in early life plays an important role for long-term health and is shaped in large part by diet. Probiotics may contribute to improvements in health, but they have not been shown to alter the community composition of the gut microbiome. Here, we found that breastfed infants could be stably colonized at high levels by provision of B. infantis EVC001, with significant changes to the overall microbiome composition persisting more than a month later, whether the infants were born vaginally or by caesarean section. This observation is consistent with previous studies demonstrating the capacity of this subspecies to utilize human milk glycans as a nutrient and underscores the importance of pairing a probiotic organism with a specific substrate. Colonization by B. infantis EVC001 resulted in significant changes to fecal microbiome composition and was associated with improvements in fecal biochemistry. The combination of human milk and an infant-associated Bifidobacterium sp. shows, for the first time, that durable changes to the human gut microbiome are possible and are associated with improved gut function. Attempts to alter intestinal dysbiosis via administration of probiotics have consistently shown that colonization with the administered microbes is transient. This study sought to determine whether provision of an initial course of Bifidobacterium longum subsp. infantis (B. infantis) would lead to persistent colonization of the probiotic organism in breastfed infants. Mothers intending to breastfeed were recruited and provided with lactation support. One group of mothers fed B. infantis EVC001 to their infants from day 7 to day 28 of life (n = 34), and the second group did not administer any probiotic (n = 32). Fecal samples were collected during the first 60 postnatal days in both groups. Fecal samples were assessed by 16S rRNA gene sequencing, quantitative PCR, mass spectrometry, and endotoxin measurement. B. infantis-fed infants had significantly higher populations of fecal Bifidobacteriaceae, in particular B. infantis, while EVC001 was fed, and this difference persisted more than 30 days after EVC001 supplementation ceased. Fecal milk oligosaccharides were significantly lower in B. infantis EVC001-fed infants, demonstrating higher consumption of human milk oligosaccharides by B. infantis EVC001. Concentrations of acetate and lactate were significantly higher and fecal pH was significantly lower in infants fed EVC001, demonstrating alterations in intestinal fermentation. Infants colonized by Bifidobacteriaceae at high levels had 4-fold-lower fecal endotoxin levels, consistent with observed lower levels of Gram-negative Proteobacteria and Bacteroidetes. IMPORTANCE The gut microbiome in early life plays an important role for long-term health and is shaped in large part by diet. Probiotics may contribute to improvements in health, but they have not been shown to alter the community composition of the gut microbiome. Here, we found that breastfed infants could be stably colonized at high levels by provision of B. infantis EVC001, with significant changes to the overall microbiome composition persisting more than a month later, whether the infants were born vaginally or by caesarean section. This observation is consistent with previous studies demonstrating the capacity of this subspecies to utilize human milk glycans as a nutrient and underscores the importance of pairing a probiotic organism with a specific substrate. Colonization by B. infantis EVC001 resulted in significant changes to fecal microbiome composition and was associated with improvements in fecal biochemistry. The combination of human milk and an infant-associated Bifidobacterium sp. shows, for the first time, that durable changes to the human gut microbiome are possible and are associated with improved gut function.


PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0241784
Author(s):  
Artem P. Gureev ◽  
Mikhail Yu. Syromyatnikov ◽  
Daria A. Ignatyeva ◽  
Valeria V. Valuyskikh ◽  
Sergey A. Solodskikh ◽  
...  

In recent years, methylene blue (MB) has attracted considerable interest as a potential drug for the treatment of methemoglobinemia and neurodegenerative diseases. MB is active against microorganisms from various taxonomic groups. However, no studies have yet been conducted on the effect of MB on the intestinal microbiome of model animals. The aim of this work was to study the effect of different concentrations of MB on the mouse gut microbiome and its relationship with the cognitive abilities of mice. We showed that a low MB concentration (15 mg/kg/day) did not cause significant changes in the microbiome composition. The Bacteroidetes/Firmicutes ratio decreased relative to the control on the 2nd and 3rd weeks. A slight decrease in the levels Actinobacteria was detected on the 3rd week of the experiment. Changes in the content of Delta, Gamma, and Epsilonproteobacteria have been also observed. We did not find significant alterations in the composition of intestinal microbiome, which could be an indication of the development of dysbiosis or other gut dysfunction. At the same time, a high concentration of MB (50 mg/kg/day) led to pronounced changes, primarily an increase in the levels of Delta, Gamma and Epsilonproteobacteria. Over 4 weeks of therapy, the treatment with high MB concentration has led to an increase in the median content of Proteobacteria to 7.49% vs. 1.61% in the control group. Finally, we found that MB at a concentration of 15 mg/kg/day improved the cognitive abilities of mice, while negative correlation between the content of Deferribacteres and cognitive parameters was revealed. Our data expand the understanding of the relationship between MB, cognitive abilities, and gut microbiome in respect to the antibacterial properties of MB.


2021 ◽  
Author(s):  
Xinyue Zhang ◽  
Kun Guo ◽  
Linjing Shi ◽  
Ting Sun ◽  
Songmei Geng

Abstract Background: Psoriasis is an inflammatory skin disease associated with multiple comorbidities and substantially diminishes patients’ quality of life. The gut microbiome has become a hot topic in psoriasis as it has been shown to affect both allergy and autoimmunity diseases in recent studies. Our objective was to identify differences in the fecal microbial composition of patients with psoriasis compared with healthy individuals to unravel the microbiota profiling in this autoimmune disease.Results: We collected fecal samples from 30 psoriasis patients and 30 healthy controls, sequenced them by 16S rRNA high-throughput sequencing, and identified the gut microbial composition using bioinformatic analyses including Quantitative Insights into Microbial Ecology (QIIME) and Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt). Our results showed that different relative abundance of certain bacterial taxa between psoriasis patients and healthy individuals, including Faecalibacterium and Megamonas, were increased in patients with psoriasis. It’s also implicated that many cytokines act as main effect molecules in the pathology of psoriasis. We selected the inflammation-related indicators that were abnormal in psoriasis patients and found the microbiome variations were associated with the level of them, especially interleukin-2 receptor showed a positive relationship with Phascolarctobacterium and a negative relationship with the dialister. The relative abundance of Phascolarctobacterium and dialister can be regard as predictors of psoriasis activity. The correlation analysis based on microbiota and Inflammation-related indicators showed that microbiota dysbiosis might induce an abnormal immune response in psoriasis. Conclusions: We concluded that the gut microbiome composition in psoriasis patients has been altered markedly and provides evidence to understand the relationship between gut microbiota and psoriasis. More mechanistic experiments are needed to determine whether the differences observed in gut microbiota are the cause or consequences of psoriasis and whether the relationship between gut microbiota and cytokines was involved.


Author(s):  
Alexander Kurilshikov ◽  
Carolina Medina-Gomez ◽  
Rodrigo Bacigalupe ◽  
Djawad Radjabzadeh ◽  
Jun Wang ◽  
...  

AbstractTo study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed whole-genome genotypes and 16S fecal microbiome data from 18,473 individuals (25 cohorts). Microbial composition showed high variability across cohorts: we detected only 9 out of 410 genera in more than 95% of the samples. A genome-wide association study (GWAS) of host genetic variation in relation to microbial taxa identified 30 loci affecting microbome taxa at a genome-wide significant (P<5×10-8) threshold. Just one locus, the lactase (LCT) gene region, reached study-wide significance (GWAS signal P=8.6×10−21); it showed an age-dependent association with Bifidobacterium abundance. Other associations were suggestive (1.94×10−10<P<5×10−8) but enriched for taxa showing high heritability and for genes expressed in the intestine and brain. A phenome-wide association study and Mendelian randomization analyses identified enrichment of microbiome trait loci SNPs in the metabolic, nutrition and environment domains and indicated food preferences and diseases as mediators of genetic effects.


2020 ◽  
Vol 7 (3) ◽  
pp. 92 ◽  
Author(s):  
Michela Cintio ◽  
Elisa Scarsella ◽  
Sandy Sgorlon ◽  
Misa Sandri ◽  
Bruno Stefanon

Several studies have underlined the interplay among host-microbiome and pathophysiological conditions of animals. Research has also focused specifically on whether and how changes in the gut microbiome have provoked the occurrence of pathological phenomena affecting cartilage and joints in humans and in laboratory animals. Here, we tried to evaluate the relationship between the gut microbiome and the hip and elbow arthritis in owned dogs. The study included 14 dogs suffering from chronic arthritis (AD) and 13 healthy dogs (HD). After the first visit and during the period of the study, the dogs, under the supervision of the owner, were fed a semi-moist complete diet supplemented with omega 3 fatty acids. Feces and blood samples were collected in the clinic at the first visit (T0) and after days (T45). The plasma C-reactive protein (CRP) was higher, and the serum vitamin B12 and folate concentrations were lower (p < 0.05) in the AD group in comparison to the HD group. Data of the fecal microbiome showed that the relative abundances of the genus Megamonas were higher in AD (p < 0.001), while the relative abundance of the families Paraprevotellaceae, Porphyromonadaceae, and Mogibacteriaceae was significantly lower in comparison to HD. The results of the study identified several bacterial groups that differed significantly in the fecal microbiome between healthy and diseased dogs. If the observed differences in fecal bacterial composition predispose dogs to hip and elbow arthritis or if these differences reflect a correlation with these conditions deserves further investigation.


2020 ◽  
Vol 8 (12) ◽  
pp. 1887
Author(s):  
Laurin Gierse ◽  
Alexander Meene ◽  
Daniel Schultz ◽  
Theresa Schwaiger ◽  
Claudia Karte ◽  
...  

Swine are regarded as promising biomedical models, but the dynamics of their gastrointestinal microbiome have been much less investigated than that of humans or mice. The aim of this study was to establish an integrated multi-omics protocol to investigate the fecal microbiome of healthy swine. To this end, a preparation and analysis protocol including integrated sample preparation for meta-omics analyses of deep-frozen feces was developed. Subsequent data integration linked microbiome composition with function, and metabolic activity with protein inventories, i.e., 16S rRNA data and expressed proteins, and identified proteins with corresponding metabolites. 16S rRNA gene amplicon and metaproteomics analyses revealed a fecal microbiome dominated by Prevotellaceae, Lactobacillaceae, Lachnospiraceae, Ruminococcaceae and Clostridiaceae. Similar microbiome compositions in feces and colon, but not ileum samples, were observed, showing that feces can serve as minimal-invasive proxy for porcine colon microbiomes. Longitudinal dynamics in composition, e.g., temporal decreased abundance of Lactobacillaceae and Streptococcaceae during the experiment, were not reflected in microbiome function. Instead, metaproteomics and metabolomics showed a rather stable functional state, as evident from short-chain fatty acids (SCFA) profiles and associated metaproteome functions, pointing towards functional redundancy among microbiome constituents. In conclusion, our pipeline generates congruent data from different omics approaches on the taxonomy and functionality of the intestinal microbiome of swine.


2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Holly M Smith ◽  
Muredach P Reilly ◽  
Jane F Ferguson

Cardiometabolic health is influenced by both diet and gut microbiome composition, however mechanisms remain unclear. The dietary-derived metabolite carnitine has been of particular interest for its potential gut microbial-mediated relationship to atherosclerosis. Using plasma carnitine as an intermediate probe, we examined the relationship between diet, gut microbiome composition, circulating metabolite levels, and measurements of cardiometabolic health. Samples (blood, stool) and data (diet, anthropometrics) were collected from 136 healthy subjects. Purified stool 16S V4 DNA was sequenced (Illumina MiSeq, 300bp paired-end reads, ~150,000 reads/sample). Plasma carnitine was analyzed by mass spectrometry. There were several dietary components significantly associated with plasma carnitine, with an overall pattern of a diet rich in animal products and refined carbohydrates (dairy, processed meats, non-whole grains and starchy vegetables) associated with higher carnitine, while monounsaturated fat intake was associated with lower carnitine. Plasma carnitine was significantly negatively correlated with several bacterial genera including Blautia (r=-0.3 p=0.001), Parabacteroides (r=-0.2, p=0.03), and Coprococcus (r=-0.389, p<0.001). Carnitine levels above the median were associated with increases in cardiometabolic risk factors including higher systolic blood pressure (SBP, 118 vs 111 mmHg, p=0.014), BMI (27 vs. 24 kg/m 2 , p=0.002), waist-hip ratio (WHR, 0.85 vs 0.8, p=0.001) as well as higher levels of blood components associated with cardiovascular risk, including circulating monocytes (p=0.007) and hemoglobin (p=0.006). Both diet and microbiome composition also associated with several risk markers (WHR, SBP, hemoglobin), albeit to a lesser extent than plasma carnitine. In conclusion, we provide evidence for inter-related relationships between diet, microbiome composition, circulating metabolites, and markers of cardiometabolic health.


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