scholarly journals The regional diversity of gut microbiome along the GI tract of male C57BL/6 mice

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Enkhchimeg Lkhagva ◽  
Hea-Jong Chung ◽  
Jinny Hong ◽  
Wai Hong Wilson Tang ◽  
Sang-Il Lee ◽  
...  

Abstract Background The proliferation and survival of microbial organisms including intestinal microbes are determined by their surrounding environments. Contrary to popular myth, the nutritional and chemical compositions, water contents, O2 contents, temperatures, and pH in the gastrointestinal (GI) tract of a human are very different in a location-specific manner, implying heterogeneity of the microbial composition in a location-specific manner. Results We first investigated the environmental conditions at 6 different locations along the GI tract and feces of ten weeks’ old male SPF C57BL/6 mice. As previously known, the pH and water contents of the GI contents at the different locations of the GI tract were very different from each other in a location-specific manner, and none of which were not even similar to those of feces. After confirming the heterogeneous nature of the GI contents in specific locations and feces, we thoroughly analyzed the composition of the microbiome of the GI contents and feces. 16S rDNA-based metagenome sequencing on the GI contents and feces showed the presence of 13 different phyla. The abundance of Firmicutes gradually decreased from the stomach to feces while the abundance of Bacteroidetes gradually increased. The taxonomic α-diversities measured by ACE (Abundance-based Coverage Estimator) richness, Shannon diversity, and Fisher’s alpha all indicated that the diversities of gut microbiome at colon and cecum were much higher than that of feces. The diversities of microbiome compositions were lowest in jejunum and ileum while highest in cecum and colon. Interestingly, the diversities of the fecal microbiome were lower than those of the cecum and colon. Beta diversity analyses by NMDS plots, PCA, and unsupervised hierarchical clustering all showed that the microbiome compositions were very diverse in a location-specific manner. Direct comparison of the fecal microbiome with the microbiome of the whole GI tracts by α-and β-diversities showed that the fecal microbiome did not represent the microbiome of the whole GI tract. Conclusion The fecal microbiome is different from the whole microbiome of the GI tract, contrary to a baseline assumption of contemporary microbiome research work.

2020 ◽  
Author(s):  
Enkhchimeg Lkhagv ◽  
Hea-Jong Chung ◽  
Jinny Hong ◽  
Wai Hong Wilson Tang ◽  
Sang-Il Lee ◽  
...  

Abstract Background: The proliferation and survival of microbial organisms including intestinal microbes are determined by their surrounding environments. Contrary to popular myth, the nutritional and chemical compositions, water contents, O2 contents, temperatures, and pH in the gastrointestinal (GI) tract of a human are very different in a location-specific manner, implying heterogeneity of the microbial composition in a location-specific manner.Results: We first investigated the environmental conditions at 6 different locations along the GI tract and feces of ten weeks’ old male SPF C57BL/6 mice. As previously known, the pH and water contents of the GI contents at the different locations of the GI tract were very different from each other in a location-specific manner, and none of which were not even similar to those of feces. After confirming the heterogeneous nature of the GI contents in specific locations and feces, we thoroughly analyzed the composition of the microbiome of the GI contents and feces. 16S rDNA-based metagenome sequencing on the GI contents and feces showed the presence of 13 different phyla. The abundance of Firmicutes gradually decreased from the stomach to feces while the abundance of Bacteroidetes gradually increased. The taxonomic α-diversities measured by ACE (Abundance-based Coverage Estimator) richness, Shannon diversity, and Fisher’s alpha all indicated that the diversities of gut microbiome at colon and cecum were much higher than that of feces. The diversities of microbiome compositions were lowest in jejunum and ileum while highest in cecum and colon. Interestingly, the diversities of the fecal microbiome were lower than those of the cecum and colon. Beta diversity analyses by NMDS plots, PCA, and unsupervised hierarchical clustering all showed that the microbiome compositions were very diverse in a location-specific manner. Direct comparison of the fecal microbiome with the microbiome of the whole GI tracts by α-and β-diversities showed that the fecal microbiome did not represent the microbiome of the whole GI tractConclusion: The fecal microbiome is different from the whole microbiome of the GI tract, contrary to a baseline assumption of contemporary microbiome research work.


2020 ◽  
Author(s):  
Enkhchimeg Lkhagv ◽  
Hea-Jong Chung ◽  
Jinny Hong ◽  
Wai Hong Wilson Tang ◽  
Sang-Il Lee ◽  
...  

Abstract Background: The proliferation and survival of microbial organisms including intestinal microbes are determined by their surrounding environments. Contrary to popular myth, the nutritional and chemical compositions, water contents, O2 contents, temperatures, and pH in the gastrointestinal (GI) tract of human are very different in a location-specific manner, implying heterogeneity of the microbial composition in a location specific manner.Results: We first investigated the environmental conditions at 6 different locations along the along the GI tract and feces of ten weeks’ old male SPF C57BL/6 mice. As previously known, the pH and water contents of the GI contents at the different location of the GI tract were very different from each other in a location-specific manner, and none of which were not even similar to those of feces. After confirming the heterogeneous nature of the GI contents in specific location and feces, we thoroughly analyzed the composition of microbiome of the GI contents and feces. Metagenome sequencing on the GI contents and feces showed presence of 13 different phyla. The abundance of Firmicutes gradually decreased from the stomach to feces while the abundance of Bacteroidetes gradually increased. The taxonomic α-diversities measured by ACE richness, Shannon diversity and Fisher’s alpha all indicated that the diversities of gut microbiota at colon and cecum were much higher than that of feces. The diversities of microbiome compositions were lowest in jejunum and ilium while highest in cecum and colon. Interestingly, the diversities of fecal microbiome were lower than those of cecum and colon. Beta diversity analyses by NMDS plots, PCA, and un-supervised hierarchical clustering all showed that the microbiome compositions were very diverse in location-specific manner. Direct comparison of the fecal microbiome with the microbiome of the whole GI tracts by α-and β-diversities showed that fecal microbiome did not represent the microbiome of the whole GI tractConclusion: The fecal microbiome is different from the whole microbiome of the GI tract, contrary to the baseline assumption in the large majority of contemporary microbiome research work.


2020 ◽  
Vol 4 (1) ◽  
pp. 23-30
Author(s):  
Margit Juhasz ◽  
Siwei Chen ◽  
Arash Khosrovi-Eghbal ◽  
Chloe Ekelem ◽  
Yessica Landaverde ◽  
...  

Background: Alopecia areata (AA) is caused by autoimmune attack of the hair follicle. The exact pathogenesis is unknown, but hypotheses include innate immunity imbalance, environmental exposures, genetic predisposition, and possibly the microbiome. The objective of this study was to characterize the skin and gut microbiome of AA patients, and compare microbial composition to healthy individuals. Methods: This was a pilot, case-control study. Scalp and fecal microbiome samples were collected from 25 AA patients, and 25 age, gender, and race-matched healthy controls in Southern California with no significant difference in demographic characteristics. After library preparation and identification of bacterial and fungal taxonomy, multivariant analysis was performed to compare AA and healthy microbiomes. Results: The AA scalp microbiome was significant for decreased Clostridia and Malasseziomycetes, and the gut microbiome was significant for decreased Bacteroidia and increased Bacilli (p<0.05) compared to healthy controls. Conclusions: The composition of the AA bacterial and fungal, scalp and gut microbiome is significantly different than healthy individuals. Future directions include using this data to characterize microbial changes associated with AA patient diet, relating to disease severity, and predicting disease progression, prognosis and/or therapeutic response.


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.


2019 ◽  
Author(s):  
Xuefeng Gao ◽  
Binbin Wu ◽  
Yonglong Pan ◽  
Shaoming Zhou ◽  
Ming Zhang ◽  
...  

ABSTRACTPurposeThis study aimed to characterize the gut microbiota in obese Shenzhen adolescents, and evaluate the influence of gender on BMI-related differences in the gut microbiome.MethodsPhysical examinations, blood pressure measurement, serological assay, and body composition evaluation were conducted on two-hundred and five adolescents from Shenzhen. Fecal microbiome composition was profiled via 16S rRNA gene sequencing. A Random Forest (RF) classifier model was built to distinguish the BMI categories based on the gut bacterial composition.ResultsFifty-six taxa consisting mainly of Firmicutes were identified that having significant associations with BMI; two OTUs belonging to Ruminococcaceae and one belonging to Lachnospiraceae had relatively strong positive correlations with body fate rate, waistline, and most of serum biochemical parameters. Based on the 56 BMI-associated OTUs, the RF model showed a robust classification accuracy (AUC 0.96) for predicting the obese phenotype. Gender-specific differences in the gut microbiome composition was obtained, and a lower relative abundance of Odoribacter was particularly found in obese boys. Functional analysis revealed a deficiency in bacterial gene contents related to PPAR signaling pathway in obese subjects for both genders; significantly lower levels of adipocytokine signaling pathway and ethylbenzene degradation were particularly detected in obese girls.ConclusionsThis study revealed unique features of gut microbiome in terms of microbial composition and metabolic functions in obese Shenzhen adolescents. The effect of geographical location, age and gender on the gut microbiome should be carefully considered in case–control studies.


Author(s):  
Soomin Jeon ◽  
Hyaekang Kim ◽  
Jina Kim ◽  
Donghyeok Seol ◽  
Jinchul Jo ◽  
...  

Recently, the concept of the “gut-brain axis” has risen and suggested that microbes in the GI tract affect the brain by modulating signal molecules. Although many pieces of research were reported in a short period, a signaling mechanism and the effects of a specific bacterial strain are still unclear.


2021 ◽  
Vol 12 ◽  
Author(s):  
Hui Wang ◽  
Gangduo Wang ◽  
Nivedita Banerjee ◽  
Yuejin Liang ◽  
Xiaotang Du ◽  
...  

Microbiome composition and function have been implicated as contributing factors in the pathogenesis of autoimmune diseases (ADs), including systemic lupus erythematosus (SLE), rheumatoid arthritis and autoimmune hepatitis (AIH). Furthermore, dysbiosis of gut microbiome is associated with impaired barrier function and mucosal immune dysregulation. However, mechanisms by which gut microbiome contributes to the ADs and whether antioxidant treatment can restore gut homeostasis and ameliorate the disease outcome are not known. This study was, therefore, focused on examining the involvement of gut microbiome and host responses in the pathogenesis of SLE using unique female mouse models (C57BL/6, MRL+/+ and MRL/lpr) of 6 and 18 weeks with varying degrees of disease progression. Fecal microbiome diversity and composition, gut oxidative stress (OS), barrier function and inflammation, as well as systemic autoimmunity were determined. Interestingly, each mouse strain had distinct bacterial community as revealed by β-diversity. A lower Firmicutes/Bacteroidetes ratio in 6-week-old MRL/lpr mice was observed, evidenced by decrease in Peptostreptococcaceae under Firmicutes phylum along with enrichment of Rikenellaceae under Bacteroidetes phylum. Additionally, we observed increases in colonic OS [4-hydroxynonenal (HNE)-adducts and HNE-specific immune complexes], permeability changes (lower tight junction protein ZO-2; increased fecal albumin and IgA levels) and inflammatory responses (increased phos-NF-κB, IL-6 and IgG levels) in 18-week-old MRL/lpr mice. These changes were associated with markedly elevated AD markers (antinuclear and anti-smooth muscle antibodies) along with hepatic portal inflammation and severe glomerulonephritis. Notably, antioxidant N-acetylcysteine treatment influenced the microbial composition (decreased Rikenellaceae; increased Akkeransiaceae, Erysipelotrichaceae and Muribaculaceae) and attenuated the systemic autoimmunity in MRL/lpr mice. Our data thus show that gut microbiome dysbiosis is associated with increased colonic OS, barrier dysfunction, inflammatory responses and systemic autoimmunity markers. These findings apart from delineating a role for gut microbiome dysbiosis, also support the contribution of gut OS, permeability changes and inflammatory responses in the pathogenesis of ADs.


2020 ◽  
Author(s):  
Xiaolin Liu ◽  
Min Dai ◽  
Yue Ma ◽  
Na Zhao ◽  
Huijie Zhang ◽  
...  

AbstractGut microbiome are studied primarily using fecal samples in humans and we gained vital knowledge of compositional and functional capacities of gastro-intestinal microbial communities. Yet, fecal materials limit our ability to investigate microbial dynamics in different locations along GI-tract (in situ), nor in finer temporal scales as they are infrequent. With a technology developed originally for fecal material transplantation, colonic transendoscopic enteral tubing, we were able to sample ileocecal microbiome twice daily, and carried out metagenomic as well as metatranscriptomic analyses. Ileocecal and fecal microbiome are similar in metagenomic profiling, yet their active genes (in metatranscriptomes) are highly distinct. Both were perturbed after laxatives and then became more similar to microbiome prior to treatment, demonstrating resilience as an innate property of gut microbiome. Ileocecal microbiome transcriptomes sampled during day and night revealed diurnal rhythmes exist in certain bacterial species and functional pathways, in particular those related to short-chain fatty acid production. Lastly, metabolomic analysis in fecal and urine samples mirrored the perturbance and recovery in gut microbiome, indicating crucial contribution of gut microbiome to many of the key metabolites involved in host health. Our study provides interesting novel insights into human gut microbiome, and demonstrates the inner resilience, diurnal rhythmes and potential consequences to the host.


2020 ◽  
Author(s):  
Jin Shang ◽  
Zhigang Ren ◽  
Ang Li ◽  
Ruixue Guo ◽  
Yiding Zhang ◽  
...  

Abstract Background Diabetic nephropathy is characterized by increased incidence, deficient diagnostic methods and poor prognosis. New idea about altered gut microbiome associated with diagnosis and development of diabetic nephropathy remains to be verified. The major aim of our study is to relate fecal microbiome to clinically diagnosed diabetic kidney disease (DKD) or pathologically identified diabetic nephropathy (defined as DN) and further evaluate diagnosis potential of microbial markers for DKD/DN. We carried out 16S rRNA sequencing on a discovery cohort consisting of 352 patients (DKD = 120, DM = diabetes mellitus = 92, Con = healthy controls = 140) to identify microbial taxa and construct DKD classifier. Functional relevance and clinic correlation of microbiome changes were performed using PICRUSt and Spearman analysis, respectively. Independent 60 DKDs and 116 non-DKDs (DM = 46, Con = 70) were used to validate the results. The same analysis was performed on DKD pathologic subtypes (DN = 22, MN = membranous nephropathy = 22). Results DKD/DM samples had a distinct microbiome signature with lower alpha-diversity and significantly different microbial composition compared with Con (P < 0.001). Expansion of opportunistic pathogens (Peptostreptococcaceae_incertae_sedis, Clostridium_sensu_stricto_1, Streptococcus, Enterococcus, Erysipelotrichaceae_incertae_sedis), sulphate-reducing bacteria (Desulfovibrio) and depletion of bacteria producing short-chain fatty acids (SCFA) (Bacteroides, Faecalibacterium, Blautia and Roseburia) were major contributors to above differences. Interestingly, mucosa-associated bacteria including Akkermansia and Ruminococcus were also increased in DKD. The combination of 11 microbial markers could separate 120 DKDs from 232 non-DKDs with an area under curve (AUC) of 88.12%. Correspondingly, diagnostic power of microbial biomarkers was evaluated in a validation cohort of 60 patients and 116 non-DKDs (AUC = 79.75%). Besides DKD-related lipid and arginine metabolism, we also observed an increase of metabolism of aromatic amino acid in DM. Additionally, microbial comparison was carried out between pathologic subtypes of DKD, which could be used to distinguish DN from MN with 77.69% AUC. Conclusion Gut microbiome-related changes were associated with pathogenesis of DKD/DN; Microbiota-targeted markers could be an alternative test for DKD diagnosis and a non-invasive choice to differentiate DKD pathologic subtypes.


Life ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 246
Author(s):  
Felix C.F. Schmitt ◽  
Martin Schneider ◽  
William Mathejczyk ◽  
Markus A. Weigand ◽  
Jane C. Figueiredo ◽  
...  

Changes in the gut microbiome have already been associated with postoperative complications in major abdominal surgery. However, it is still unclear whether these changes are transient or a long-lasting effect. Therefore, the aim of this prospective clinical pilot study was to examine long-term changes in the gut microbiota and to correlate these changes with the clinical course of the patient. Methods: In total, stool samples of 62 newly diagnosed colorectal cancer patients undergoing primary tumor resection were analyzed by 16S-rDNA next-generation sequencing. Stool samples were collected preoperatively in order to determine the gut microbiome at baseline as well as at 6, 12, and 24 months thereafter to observe longitudinal changes. Postoperatively, the study patients were separated into two groups—patients who suffered from postoperative complications (n = 30) and those without complication (n = 32). Patients with postoperative complications showed a significantly stronger reduction in the alpha diversity starting 6 months after operation, which does not resolve, even after 24 months. The structure of the microbiome was also significantly altered from baseline at six-month follow-up in patients with complications (p = 0.006). This was associated with a long-lasting decrease of a large number of species in the gut microbiota indicating an impact in the commensal microbiota and a long-lasting increase of Fusobacterium ulcerans. The microbial composition of the gut microbiome shows significant changes in patients with postoperative complications up to 24 months after surgery.


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