scholarly journals Fecal microbiota transplantation mitigates bone loss by improving gut microbiome composition and gut barrier function in aged rats

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12293
Author(s):  
Sicong Ma ◽  
Ning Wang ◽  
Pu Zhang ◽  
Wen Wu ◽  
Lingjie Fu

Background Gut microbiota (GM) dysbiosis is closely related to bone loss and the occurrence of osteoporosis in animals and human. However, little is known about the effect and the mechanisms of fecal microbiota transplantation (FMT) on bone in the treatment of senile osteoporosis. Methods Aged female rats were randomly divided into the FMT group and the control group. 3-month-old female rats were used as fecal donors. The rats were sacrificed at 12 and 24 weeks following transplantation and the serum, intestine, bone, and feces were collected for subsequent analyses. Results The bone turnover markers of osteocalcin, procollagen type 1 N-terminal propeptide (P1NP), and carboxy-terminal peptide (CTX) decreased significantly at 12 and 24 weeks following FMT (P < 0.05). At 12 weeks following transplantation, histomorphometric parameters including the bone volume (BV), trabecular bone volume fraction (BV/TV), trabecular number (Tb.N), and trabecular thickness (Tb.Th) of the FMT group were comparable to the control group. However, at 24 weeks following transplantation, these parameters of the FMT group were significantly higher than those of the control group (P < 0.05). Besides, the GM aggregated at 12 and 24 weeks following FMT, and the ecological distance was close between the rats in the FMT group and the donor rats. Alpha diversity, shown by the Shannon index and Simpson index, and the Firmicutes/Bacteroidetes ratio decreased significantly after FMT at 24 weeks. Furthermore, FMT restored the GM composition in aged rats at the phylum and family level, and the intestinal microbiota of the aged rats was similar to that of the donor rats. Correlation network analysis indirectly suggested the causality of FMT on alleviating osteoporosis. FMT improved the intestinal structure and up-regulated the expression of tight junction proteins of occludin, claudin, and ZO-1, which might be associated with the protective effects of FMT on bone. Conclusions GM transplanted from young rats alleviated bone loss in aged rats with senile osteoporosis by improving gut microbiome composition and intestinal barrier function. These data might provide a scientific basis for future clinical treatment of osteoporosis through FMT.

2020 ◽  
Vol 41 (5) ◽  
pp. 678-685 ◽  
Author(s):  
Pei-pei Zhang ◽  
Lin-lin Li ◽  
Xue Han ◽  
Qin-wei Li ◽  
Xu-hua Zhang ◽  
...  

2021 ◽  
Author(s):  
Eric W. Jones ◽  
Jean M. Carlson ◽  
David A. Sivak ◽  
William B. Ludington

AbstractObservational studies reveal substantial variability in microbiome composition across individuals. While some of this variability can be explained by external factors like environmental, dietary, and genetic differences between individuals, in this paper we show that for the model organism Drosophila melanogaster the process of microbiome assembly is inherently stochastic and contributes a baseline level of microbiome variability even among organisms that are identically reared, housed, and fed. In germ-free flies fed known combinations of bacterial species, we find that some species colonize more frequently than others even when fed at the same high concentration. We develop a new ecological technique that infers the presence of interactions between bacterial species based on their colonization odds in different contexts, requiring only presence/absence data from two-species experiments. We use a progressive sequence of probabilistic models, in which the colonization of each bacterial species is treated as an independent stochastic process, to reproduce the empirical distributions of colonization outcomes across experiments. We find that incorporating context-dependent interactions substantially improves the performance of the models. Stochastic, context-dependent microbiome assembly underlies clinical therapies like fecal microbiota transplantation and probiotic administration, and should inform the design of synthetic fecal transplants and dosing regimes.Significance StatementIndividuals are constantly exposed to microbial organisms that may or may not colonize their gut microbiome, and newborn individuals assemble their microbiomes through a number of these acquisition events. Since microbiome composition has been shown to influence host physiology, a mechanistic understanding of community assembly has potentially therapeutic applications. In this paper we study microbiome acquisition in a highly-controlled setting using germ-free fruit flies inoculated with specific bacterial species at known abundances. Our approach revealed that acquisition events are stochastic, and the colonization odds of different species in different contexts encode ecological information about interactions. These findings have consequences for microbiome-based therapies like fecal microbiota transplantation that attempt to modify a person’s gut microbiome by deliberately introducing foreign microbes.


2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Fengqiong Liu ◽  
Shanliang Ye ◽  
Xin Zhu ◽  
Xuesong He ◽  
Shengzhou Wang ◽  
...  

Abstract Background To investigate the potential beneficial effect of fecal microbiota transplantation (FMT) on gastrointestinal symptoms, gut dysbiosis and immune status in discharged COVID-19 patients. Case presentation A total of 11 COVID-19 patients were recruited in April, 2020, about one month on average after they were discharged from the hospital. All subjects received FMT for 4 consecutive days by oral capsule administrations with 10 capsules for each day. In total, 5 out of 11 patients reported to be suffered from gastrointestinal symptoms, which were improved after FMT. After FMT, alterations of B cells were observed, which was characterized as decreased naive B cell (P = 0.012) and increased memory B cells (P = 0.001) and non-switched B cells (P = 0.012).The microbial community richness indicated by operational taxonomic units number, observed species and Chao1 estimator was marginally increased after FMT. Gut microbiome composition of discharged COVID-19 patients differed from that of the general population at both phylum and genera level, which was characterized with a lower proportion of Firmicutes (41.0%) and Actinobacteria (4.0%), higher proportion of Bacteroidetes (42.9%) and Proteobacteria (9.2%). FMT can partially restore the gut dysbiosis by increasing the relative abundance of Actinobacteria (15.0%) and reducing Proteobacteria (2.8%) at the phylum level. At the genera level, Bifidobacterium and Faecalibacterium had significantly increased after FMT. Conclusions After FMT, altered peripheral lymphocyte subset, restored gut microbiota and alleviated gastrointestinal disorders were observe, suggesting that FMT may serve as a potential therapeutic and rehabilitative intervention for the COVID-19.


F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 997 ◽  
Author(s):  
Derek M. Lin ◽  
Henry C. Lin

Bacteriophages are the most prominent members of the gut microbiome, outnumbering their bacterial hosts by a factor of 10. Phages are bacteria-specific viruses that are gaining attention as highly influential regulators of the gut bacterial community. Dysregulation of the gut bacterial community contributes to dysbiosis, a microbiome disorder characterized by compositional and functional changes that contribute to disease. A role for phages in gut microbiome dysbiosis is emerging with evidence that the gut phage community is altered in dysbiosis-associated disorders such as colorectal cancer and inflammatory bowel disease. Several recent studies have linked successful fecal microbiota transplantation to uptake of the donor’s gut phage community, offering some insight into why some recipients respond to treatment whereas others do not. Here, we review the literature supporting a role for phages in mediating the gut bacterial community, giving special attention to Western diet dysbiosis as a case study to demonstrate a theoretical phage-based mechanism for the establishment and maintenance of dysbiosis.


2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Sandra Mrozinska ◽  
Piotr Radkowski ◽  
Tomasz Gosiewski ◽  
Magdalena Szopa ◽  
Malgorzata Bulanda ◽  
...  

Background. Type 2 diabetes mellitus (T2DM) is determined by genetic and environmental factors. There have been many studies on the relationship between the composition of the gastrointestinal bacterial flora, T2DM, and obesity. There are no data, however, on the gut microbiome structure in monogenic forms of the disease including Maturity Onset Diabetes of the Young (MODY).Methods. The aim of the investigation was to compare the qualitative parameters of the colonic flora in patients with HNF1A-MODY and T2DM and healthy individuals. 16S sequencing of bacterial DNA isolated from the collected fecal samples using the MiSeq platform was performed.Results. There were significant between-group differences in the bacterial profile. At the phylum level, the amount of Proteobacteria was higher (p=0.0006) and the amount of Bacteroidetes was lower (p=0.0005) in T2DM group in comparison to the control group. In HNF1A-MODY group, the frequency of Bacteroidetes was lower than in the control group (p=0.0143). At the order level, Turicibacterales was more abundant in HNF1A-MODY group than in T2DM group.Conclusions. It appears that there are differences in the gut microbiome composition between patients with HNF1A-MODY and type 2 diabetes. Further investigation on this matter should be conducted.


F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 46 ◽  
Author(s):  
Eamonn M.M Quigley ◽  
Prianka Gajula

We are in the midst of “the microbiome revolution”—not a day goes by without some new revelation on the potential role of the gut microbiome in some disease or disorder. From an ever-increasing recognition of the many roles of the gut microbiome in health and disease comes the expectation that its modulation could treat or prevent these very same diseases. A variety of interventions could, at least in theory, be employed to alter the composition or functional capacity of the microbiome, ranging from diet to fecal microbiota transplantation (FMT). For some, such as antibiotics, prebiotics, and probiotics, an extensive, albeit far from consistent, literature already exists; for others, such as other dietary supplements and FMT, high-quality clinical studies are still relatively few in number. Not surprisingly, researchers have turned to the microbiome itself as a source for new entities that could be used therapeutically to manipulate the microbiome; for example, some probiotic strains currently in use were sourced from the gastrointestinal tract of healthy humans. From all of the extant studies of interventions targeted at the gut microbiome, a number of important themes have emerged. First, with relatively few exceptions, we are still a long way from a precise definition of the role of the gut microbiome in many of the diseases where a disturbed microbiome has been described—association does not prove causation. Second, while animal models can provide fascinating insights into microbiota–host interactions, they rarely recapitulate the complete human phenotype. Third, studies of several interventions have been difficult to interpret because of variations in study population, test product, and outcome measures, not to mention limitations in study design. The goal of microbiome modulation is a laudable one, but we need to define our targets, refine our interventions, and agree on outcomes.


2020 ◽  
Author(s):  
Dong-Juan Xu ◽  
Kai Cheng Wang ◽  
Lin-Bo Yuan ◽  
Qiong-Qiong Lin ◽  
Hong-Fei Li ◽  
...  

Abstract Background — With the establishment of the concept of the gut–brain axis, increasing evidence has shown that the gut microbiome plays an important role in the pathogenesis of cardiovascular diseases. Gut bacteria can transform dietary choline, L-carnitine, and trimethylamine N -oxide (TMAO) into trimethylamine, which can be oxidized into TMAO again in the liver and participate in atherogenesis. However, only few studies have described alterations in the gut microbiota composition and function in cardioembolic (CE) and large artery atherosclerotic (LAA) strokes. Methods and Results — A case–control study was performed on patients with LAA and CE strokes. TMAO was determined via liquid chromatography tandem mass spectrometry. Gut microbiome was profiled through Illumina sequencing of the 16S ribosomal RNA gene (V4–V5 regions). The TMAO levels in the plasma of patients with LAA and CE strokes were significantly increased (TMAO: LAA stroke, 2931±456.4 ng/mL vs. CE stroke, 4220±577.6 ng/mL vs. control, 1663±117.8 ng/mL; P < 0.05). The TMAO level in patients with LAA stroke was positively correlated with the carotid plaque area (rho = 0.333, 95% confidence interval = 0.08 to 0.55, and P = 0.0093). The composition and function of gut microbiomes in the LAA and CE stroke groups were significantly different from those of the asymptomatic control. In addition to the significantly increased α and β diversities, the gut microbiome composition and function showed that the LAA group had more microorganisms than the asymptomatic control group; such microorganisms convert dietary source choline, TMAO to TMA. Parabacteroides and Streptococcus exhibited the strongest association with LAA and CE strokes. Conclusions — This study established the compositional and functional alterations of gut microbiomes in patients with LAA and CE strokes and the relationship between plasma TMAO and gut microbiota. The findings suggest the potential of using gut microbiota as a biomarker for patients with LAA and CE strokes.


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.


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