scholarly journals Oral Administration ofPorphyromonas gingivalisAlters the Gut Microbiome and Serum Metabolome

mSphere ◽  
2018 ◽  
Vol 3 (5) ◽  
Author(s):  
Tamotsu Kato ◽  
Kyoko Yamazaki ◽  
Mayuka Nakajima ◽  
Yasuhiro Date ◽  
Jun Kikuchi ◽  
...  

ABSTRACTPeriodontal disease induced by periodontopathic bacteria likePorphyromonas gingivalisis demonstrated to increase the risk of metabolic, inflammatory, and autoimmune disorders. Although precise mechanisms for this connection have not been elucidated, we have proposed mechanisms by which orally administered periodontopathic bacteria might induce changes in gut microbiota composition, barrier function, and immune system, resulting in an increased risk of diseases characterized by low-grade systemic inflammation. Accumulating evidence suggests a profound effect of altered gut metabolite profiles on overall host health. Therefore, it is possible thatP. gingivaliscan affect these metabolites. To test this, C57BL/6 mice were administered withP. gingivalisW83 orally twice a week for 5 weeks and compared with sham-inoculated mice. The gut microbial communities were analyzed by pyrosequencing the 16S rRNA genes. Inferred metagenomic analysis was used to determine the relative abundance of KEGG pathways encoded in the gut microbiota. Serum metabolites were analyzed using nuclear magnetic resonance (NMR)-based metabolomics coupled with multivariate statistical analyses. Oral administration ofP. gingivalisinduced a change in gut microbiota composition. The distributions of metabolic pathways differed between the two groups, including those related to amino acid metabolism and, in particular, the genes for phenylalanine, tyrosine, and tryptophan biosynthesis. Also, alanine, glutamine, histidine, tyrosine, and phenylalanine were significantly increased in the serum ofP. gingivalis-administered mice. In addition to altering immune modulation and gut barrier function, oral administration ofP. gingivalisaffects the host’s metabolic profile. This supports our hypothesis regarding a gut-mediated systemic pathology resulting from periodontal disease.IMPORTANCEIncreasing evidence suggest that alterations of the gut microbiome underlie metabolic disease pathology by modulating gut metabolite profiles. We have shown that orally administeredPorphyromonas gingivalis, a representative periodontopathic bacterium, alters the gut microbiome; that may be a novel mechanism by which periodontitis increases the risk of various diseases. Given the association between periodontal disease and metabolic diseases, it is possible thatP. gingivaliscan affect the metabolites. Metabolite profiling analysis demonstrated that several amino acids related to a risk of developing diabetes and obesity were elevated inP. gingivalis-administered mice. Our results revealed that the increased risk of various diseases byP. gingivalismight be mediated at least in part by alteration of metabolic profiles. The findings should add new insights into potential links between periodontal disease and systemic disease for investigators in periodontal disease and also for investigators in the field of other diseases, such as metabolic diseases.


2020 ◽  
Author(s):  
Taís Silveira Assmann ◽  
Amanda Cuevas-Sierra ◽  
José Ignacio Riezu-Boj ◽  
Fermin Milagro ◽  
J Alfredo Martínez

Abstract Background: Unbalances in microRNAs (miRNA) and gut microbiota patterns have been proposed as putative factors concerning onset and development of obesity and other metabolic diseases. However, the determinants that mediate the interactions between miRNAs and the gut microbiome impacting on obesity are scarcely understood. Thus, the aim of this article was to investigate possible interactions between circulating miRNAs and gut microbiota composition in obesity. Method: The analyzed sample comprised 78 subjects with obesity [cases, body mass index (BMI): 30 – 40 kg/m2] and 25 eutrophic individuals (controls, BMI £ 25 kg/m2). The expression of 96 miRNAs was investigated in plasma of all individuals using miRCURY LNA miRNA Custom PCR Panels (Exiqon). Bacterial DNA sequencing was performed following the Illumina 16S protocol. The FDR (Benjamini-Hochberg test, q-value) correction was used for multiple comparison analyses.Results: A total of 26 circulating miRNAs and 12 bacterial species were found differentially expressed between cases and controls. Interestingly, an interaction among three miRNAs (miR-130b-3p, miR-185-5p, and miR-21-5p) with Bacteroides eggerthi, and BMI levels was evidenced (r2= 0.148, P= 0.004). Those miRNAs that correlated with obesity-associated gut bacteria abundance are known to regulate target genes that participate in metabolism-related pathways, such as fatty acid degradation, carbohydrate digestion and absorption, insulin signaling, and glycerolipid metabolism. Conclusion: This study characterized an interaction between the abundance of 4 bacterial species and 14 circulating miRNAs in relation to body adiposity. Moreover, the current study also suggests that miRNAs may serve as a communication mechanism between the gut microbiome and human hosts. Clinical trial registration: clinicaltrials.gov (reg. no. NCT02737267).



2021 ◽  
Vol 49 (08) ◽  
pp. 1897-1912
Author(s):  
Jeon-Kyung Kim ◽  
Eun Kyu Lee ◽  
Chu Hyun Bae ◽  
Soo-Dong Park ◽  
Jae-Jung Shim ◽  
...  

Ginsenosides of orally administered red ginseng (RG) extracts are metabolized and absorbed into blood. Here, we examined the pharmacokinetic profiles of ginsenosides Rd and Rg3 in mice orally gavaged with RG, then investigated the correlations between these and gut microbiota composition. RG water extract (RGw), RG ethanol extract (RGe), or fermented RGe (fRGe) was orally gavaged in mice. The plasma concentrations of the ginsenosides were determined, and the gut microbiota composition was analyzed. RGe and fRGe-treated mice showed higher plasma concentration levels of ginsenoside Rd compared with RGw-treated mice; particularly, ginsenoside Rd absorbed was substantially high in fRGe-treated mice. Oral administration of RG extracts modified the gut microbiota composition; the modified gut microbiota, such as Peptococcaceae, Rikenellaceae, and Hungateiclostridiaceae, were closely correlated with the absorption of ginsenosides, such as Rd and Rg3. These results suggest that oral administration of RG extracts can modify gut microbiome, which may consequently affect the bioavailability of RG ginsenosides.



2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rafael Corrêa ◽  
Igor de Oliveira Santos ◽  
Heloísa Antoniella Braz-de-Melo ◽  
Lívia Pimentel de Sant’Ana ◽  
Raquel das Neves Almeida ◽  
...  

AbstractGut microbiota composition can modulate neuroendocrine function, inflammation, and cellular and immunological responses against different pathogens, including viruses. Zika virus (ZIKV) can infect adult immunocompetent individuals and trigger brain damage and antiviral responses. However, it is not known whether ZIKV infection could impact the gut microbiome from adult immunocompetent mice. Here, we investigated modifications induced by ZIKV infection in the gut microbiome of immunocompetent C57BL/6J mice. Adult C57BL/6J mice were infected with ZIKV and the gut microbiota composition was analyzed by next-generation sequencing of the V4 hypervariable region present in the bacterial 16S rDNA gene. Our data showed that ZIKV infection triggered a significant decrease in the bacteria belonging to Actinobacteria and Firmicutes phyla, and increased Deferribacteres and Spirochaetes phyla components compared to uninfected mice. Interestingly, ZIKV infection triggered a significant increase in the abundance of bacteria from the Spirochaetaceae family in the gut microbiota. Lastly, we demonstrated that modulation of microbiota induced by ZIKV infection may lead to intestinal epithelium damage and intense leukocyte recruitment to the intestinal mucosa. Taken together, our data demonstrate that ZIKV infection can impact the gut microbiota composition and colon tissue homeostasis in adult immunocompetent mice.



2018 ◽  
Vol 48 (6) ◽  
pp. 962-972 ◽  
Author(s):  
Rio Jati Kusuma ◽  
Aviria Ermamilia

Purpose Iron deficiency anemia (IDA) is one of the most major micronutrient deficiencies worldwide. Food fortification is one strategy for reducing IDA in the population despite concern regarding the gut pathogenic bacteria overgrowth. The purpose of this study was to evaluate the effect of iron encapsulation in banana peel matrix on iron status and gut microbiota composition in iron deficiency anemia. Design/methodology/approach Anemia was induced in 35 male Sprague Dawley rats of age two weeks by the administration of iron-free diet for two weeks. Rats then randomly divided into control, iron-fortified tempeh (temFe) dose 10 and 20 ppm, iron matrix-fortified tempeh dose 10 and 20 ppm and iron matrix fortified tempeh dose 10 and 20 ppm with probiotic mixture. Blood was drawn at Weeks 2 and 6 for hemoglobin and serum iron analysis. Rats were sacrificed at the end of Week 6, and cecal contents were collected for Lactobacillus, Bifidobacteria and Enterobactericeae analysis. Findings Hemoglobin and serum iron were significantly increased (p < 0.05) in all iron-fortified group with the highest value found in iron matrix dose 20 ppm (10.71 ± 0.15 g/dl and 335.83 ± 2.17 µg/dl, respectively). The cecal Lactobacillus and Bifidobacteria did not differ significantly between groups. Cecal Enterobactericeae was significantly different (p < 0.05) among groups with the lowest level in the temFe-20 (2.65 ± 0.78 log CFU) group. Research limitations/implications The use of commercial inoculum instead of pure Rhizopus oligosporus mold for developing the fortified tempeh may impact the effect of product on cecal gut microbiota composition, as different molds and lactic acid bacteria can grow in tempeh when using commercial inoculum. Social implications In Indonesia, iron fortification is conducted primarily in noodles and flour that limits the impact of iron fortification for reducing IDA in population. Iron fortification in food that was daily consumed by people, that is, tempeh, is potential strategy in reducing IDA in population. Originality/value Tempeh fortification using encapsulated iron improved iron status and gut microbiota composition in iron deficiency anemia.



2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S896-S897
Author(s):  
Faris S Alnezary ◽  
Tasnuva Rashid ◽  
Khurshida Begum ◽  
Travis J Carlson ◽  
Anne J Gonzales-Luna ◽  
...  

Abstract Background Antimicrobials disrupt the gut microbiota by reducing gut microbiome diversity and quantity. Galleria mellonella provides an invertebrate model that is inexpensive, easy to maintain, and does not require specialized equipment. This study investigated the feasibility of using G. mellonella as an in vivo model to evaluate the effect of different antimicrobials on gut microbiota. Methods To determine baseline gut microbiota composition, the gut contents of G. mellonella were extracted and genomic DNA underwent shotgun meta-genomic sequencing. To determine the effect of infection and antibiotic use, 30 larvae were injected (left proleg) with ~1 × 105 colony-forming unit (cfu) of methicillin-resistant Staphylococcus aureus (MRSA) and were randomized 1:1:1 to treatment with vancomycin (20 mg/kg) or a natural antimicrobial (Nigella sativa seed oil, 70 mg/kg; NS oil), or a combination. The larvae were kept at 37°C post-infection and monitored daily for 72 hours for activity, extent of cocoon formation/growth, melanization, and survival. Two larvae from each group were randomly selected and homogenized with PBS as controls. After 24 hours of incubation, gut contents were extracted and plated for MRSA and Enterococcus cfu counts. Results Metagenomics analysis showed the gut microbiota composition of G. mellonella larvae was dominated by a subset of closely-related Enterococcus species. After 24 hours of exposure, mean Enterococcus counts were 4 × 103 cfu in the vancomycin arm and 6.2 × 104 cfu in the NS oil arm. Mean MRSA counts were 3.3 × 105 cfu in vancomycin arm and 1.5 × 104 cfu in NS oil arm. The combination of vancomycin and NS oil had higher Enterococcus counts than the vancomycin alone arm (6.3 × 104 cfu vs. 4 × 103 cfu, respectively), suggesting that NS oil may have a role in protecting the gut microbiota. Conclusion This study provides preliminary evidence to support the potential use of G. mellonella to assess the in vivo effect of a natural and synthetic antimicrobial on the gut microbiota. Disclosures All authors: No reported disclosures.



2020 ◽  
Vol 70 (1) ◽  
Author(s):  
Yinlong Cheng ◽  
Yining Li ◽  
Yonghong Xiong ◽  
Yixin Zou ◽  
Siyu Chen ◽  
...  

Abstract Purpose To investigate the effect of liver-specific knockdown of ANGPTL8 on the structure of the gut microbiota. Methods We constructed mice with liver-specific ANGPTL8 knockdown by using an adeno-associated virus serotype 8 (AAV8) system harbouring an ANGPTL8 shRNA. We analysed the structure and function of the gut microbiome through pyrosequencing and KEGG (Kyoto Encyclopedia of Genes and Genomes) functional prediction. Results Compared with controls, ANGPTL8 shRNA reduced the Simpson index and Shannon index (p < 0.01) of the gut microbiota in mice. At the phylum level, the sh-ANGPTL8 group showed a healthier gut microbiota composition than controls (Bacteroidetes: controls 67.52%, sh-ANGPTL8 80.75%; Firmicutes: controls 10.96%, sh-ANGPTL8 8.58%; Proteobacteria: controls 9.29%, sh-ANGPTL8 0.98%; F/B ratio: controls 0.16, sh-ANGPTL8 0.11). PCoA and UPGMA analysis revealed a significant difference in microbiota composition, while KEGG analysis revealed a significant difference in microbiota function between controls and the sh-ANGPTL8 group. Conclusion Our results revealed that inhibition of ANGPTL8 signalling altered the structure of the gut microbiome, which might further affect the metabolism of mice. We have thus identified ANGPTL8 as a novel hepatogenic hormone potentially involving the liver-gut axis and regulating the structure of the gut microbiota.



2020 ◽  
Vol 11 (6) ◽  
pp. 5581-5594 ◽  
Author(s):  
Yohanna de Oliveira ◽  
Raissa Georgianna Silva Cavalcante ◽  
Marinaldo Pacífico Cavalcanti Neto ◽  
Marciane Magnani ◽  
Valdir de Andrade Braga ◽  
...  

Maternal dyslipidemia alters the gut microbiota composition and contributes to the development of arterial hypertension (AH) in offspring.



2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Jessica C. Ralston ◽  
Kathleen A.J. Mitchelson ◽  
Gina M. Lynch ◽  
Tam T.T. Tran ◽  
Conall R. Strain ◽  
...  

AbstractReduced inflammatory signaling (IL-1RI-/-) alters metabolic responses to dietary challenges (1). Inflammasome deficiency (e.g. IL-18-/-, Asc-/-) can modify gut microbiota concomitant with hepatosteatosis; an effect that was transferable to wild-type (WT) mice by co-housing (2). Taken together, this evidence suggests that links between diet, microbiota and IL-1RI-signaling can influence metabolic health. Our aim was to determine whether IL-1RI-mediated signaling interacted with the gut microbiome to impact metabolic tissue functionality in a diet-specific fashion. Male WT (C57BL/J6) and IL-1RI-/- mice were fed either high-fat diet (HFD; 45% kcal) or low-fat diet (LFD; 10% kcal) for 24 weeks and were housed i) separately by genotype or ii) with genotypes co-housed together (i.e. isolated vs shared microbial environment; n = 8–10 mice per group). Glucose tolerance and insulin secretion response (1.5 g/kg i.p.), gut microbiota composition and caecal short-chain fatty acids (SCFA) were assessed. Liver and adipose tissue were harvested and examined for triacylglycerol (TAG) formation, cholesterol and metabolic markers (Fasn, Cpt1α, Pparg, Scd1, Dgat1/2), using histology, gas-chromatography and RT-PCR, respectively. Statistical analysis included 1-way or 2-way ANOVA, where appropriate, with Bonferroni post-hoc correction. Co-housing significantly affected gut microbiota composition, illustrated by clustering in PCoA (unweighted UniFrac distance) of co-housed mice but not their single-housed counterparts, on both HFD and LFD. The taxa driving these differences were primarily from Lachnospiraceae and Ruminococcaceae families. Single-housed WT had lower hepatic weight, TAG, cholesterol levels and Fasn despite HFD, an effect lost in their co-housed counterparts, who aligned more to IL-1RI-/- hepatic lipid status. Hepatic Cpt1α was lowest in co-housed WT. Adipose from IL-1RI-/- groups on HFD displayed increased adipocyte size and reduced adipocyte number compared to WT groups, but greater lipogenic potential (Pparg, Scd1, Dgat2) alongside a blunted IL-6 response to pro-inflammatory stimuli (~32%, P = 0.025). Whilst caecal SCFA concentrations were not different between groups, single-housed IL-1RI-/- adipocytes showed greatest sensitivity to SCFA-induced lipogenesis. Interestingly, differences in tissue functionality and gut microbiome occurred despite unaltered glucose tolerance; although there was a trend for phenotypic transfer of body weight via co-housing. For all endpoints examined, similar genotype/co-housing effects were observed for both HFD and LFD with the greatest impacts seen in HFD-fed mice. In conclusion, while the gut microbiome may be an important consideration in dietary interventions, these results question the magnitude of its impact in relation to the IL-1RI-dependent immunometabolism-glucose homeostasis axis.



Genes ◽  
2019 ◽  
Vol 10 (10) ◽  
pp. 748 ◽  
Author(s):  
Jin-Young Lee ◽  
Mohamed Mannaa ◽  
Yunkyung Kim ◽  
Jehun Kim ◽  
Geun-Tae Kim ◽  
...  

The aim of this study was to investigate differences between the gut microbiota composition in patients with rheumatoid arthritis (RA) and those with osteoarthritis (OA). Stool samples from nine RA patients and nine OA patients were collected, and DNA was extracted. The gut microbiome was assessed using 16S rRNA gene amplicon sequencing. The structures and differences in the gut microbiome between RA and OA were analyzed. The analysis of diversity revealed no differences in the complexity of samples. The RA group had a lower Bacteroidetes: Firmicutes ratio than did the OA group. Lactobacilli and Prevotella, particularly Prevotella copri, were more abundant in the RA than in the OA group, although these differences were not statistically significant. The relative abundance of Bacteroides and Bifidobacterium was lower in the RA group. At the species level, the abundance of certain bacterial species was significantly lower in the RA group, such as Fusicatenibacter saccharivorans, Dialister invisus, Clostridium leptum, Ruthenibacterium lactatiformans, Anaerotruncus colihominis, Bacteroides faecichinchillae, Harryflintia acetispora, Bacteroides acidifaciens, and Christensenella minuta. The microbial properties of the gut differed between RA and OA patients, and the RA dysbiosis revealed results similar to those of other autoimmune diseases, suggesting that a specific gut microbiota pattern is related to autoimmunity.



Nutrients ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 3836
Author(s):  
Cristina Iribarren ◽  
Maria K. Magnusson ◽  
Louise K. Vigsnæs ◽  
Imran Aziz ◽  
Ingvild Dybdrodt Amundsen ◽  
...  

Background: Human milk oligosaccharide supplementation safely modulates fecal bifidobacteria abundance and holds the potential to manage symptoms in irritable bowel syndrome (IBS). Here, we aimed to determine the role of a 4:1 mix of 2′-O-fucosyllactose and lacto-N-neotetraose (2′FL/LNnT) on the modulation of the gut microbiota composition and host mucosal response, as well as the link between the bifidobacteria abundance and metabolite modulation, in IBS patients. Methods: Biological samples were collected from IBS patients (n = 58) at baseline and week 4 post-supplementation with placebo, 5 g or 10 g doses of 2′FL/LNnT. The gut microbiota composition, metabolite profiles and expression of genes related to host mucosal response were determined. Results: Moderate changes in fecal, but not mucosal, microbial composition (β-diversity) was observed during the intervention with higher dissimilarity observed within individuals receiving 10g 2′FL/LNnT compared to placebo. Both fecal and mucosal Bifidobacterium spp. increased after 2′FL/LNnT intake, with increased proportions of Bifidobacterium adolescentis and Bifidobacterium longum. Moreover, the intervention modulated the fecal and plasma metabolite profiles, but not the urine metabolite profile or the host mucosal response. Changes in the metabolite profiles were associated to changes in bifidobacteria abundance. Conclusion: Supplementation with 2′FL/LNnT modulated the gut microbiota, fecal and plasma metabolite profiles, but not the host mucosal response in IBS. Furthermore, the bifidogenic effect was associated with metabolite modulation. Overall, these findings support the assertion that 2′FL/LNnT supplementation modulate the intestinal microenvironment of patients with IBS, potentially related to health.



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