scholarly journals Berberine Blocks the Relapse of Clostridium difficile Infection in C57BL/6 Mice after Standard Vancomycin Treatment

2015 ◽  
Vol 59 (7) ◽  
pp. 3726-3735 ◽  
Author(s):  
Zhi Lv ◽  
Guoli Peng ◽  
Weihua Liu ◽  
Hufeng Xu ◽  
JianRong Su

ABSTRACTVancomycin is a preferred antibiotic for treatingClostridium difficileinfection (CDI) and has been associated with a rate of recurrence of CDI of as high as 20% in treated patients. Recent studies have suggested that berberine, an alternative medical therapy for gastroenteritis and diarrhea, exhibits several beneficial effects, including induction of anti-inflammatory responses and restoration of the intestinal barrier function. This study investigated the therapeutic effects of berberine on preventing CDI relapse and restoring the gut microbiota in a mouse model. Berberine was administered through gavage to C57BL/6 mice with established CDI-induced intestinal injury and colitis. The disease activity index (DAI), mean relative weight, histopathology scores, and levels of toxins A and B in fecal samples were measured. An Illumina sequencing-based analysis of 16S rRNA genes was used to determine the overall structural change in the microbiota in the mouse ileocecum. Berberine administration significantly promoted the restoration of the intestinal microbiota by inhibiting the expansion of members of the familyEnterobacteriaceaeand counteracting the side effects of vancomycin treatment. Therapy consisting of vancomycin and berberine combined prevented weight loss, improved the DAI and the histopathology scores, and effectively decreased the mortality rate. Berberine prevented CDIs from relapsing and significantly improved survival in the mouse model of CDI. Our data indicate that a combination of berberine and vancomycin is more effective than vancomycin alone for treating CDI. One of the possible mechanisms by which berberine prevents a CDI relapse is through modulation of the gut microbiota. Although this conclusion was generated in the case of the mouse model, use of the combination of vancomycin and berberine and represent a novel therapeutic approach targeting CDI.

2020 ◽  
Vol 11 ◽  
Author(s):  
Zhen Wang ◽  
Junfeng Lu ◽  
Jingwei Zhou ◽  
Weiwei Sun ◽  
Yang Qiu ◽  
...  

Obesity and related metabolic disorders are associated with intestinal microbiota dysbiosis, disrupted intestinal barrier and chronic inflammation. Shen-Yan-Fang-Shuai formula (SYFSF) is a traditional Chinese herbal formula composed of Astragali Radix, Radix Angelicae Sinensis, Rheum Officinale Baill, and four other herbs. In this study, we identified that SYFSF treatment prevented weight gain, low-grade inflammation and insulin resistance in high-fat diet (HFD)-fed mice. SYFSF also substantially improved gut barrier function, reduced metabolic endotoxemia, as well as systemic inflammation. Sequencing of 16S rRNA genes obtained from fecal samples demonstrated that SYFSF attenuated HFD-induced gut dysbiosis, seen an decreased Firmicutes to Bacteroidetes ratios. Microbial richness and diversity were also higher in the SYFSF-treated HFD group. Furthermore, similar therapeutic effects and changes in gut microbiota profile caused by SYFSF could be replicated by fecal microbiota transfer (FMT). Taken together, our study highlights the efficacy of SYFSF in preventing obesity and related metabolic disorders. Its therapeutic effect is associated with the modulation of gut microbiota, as a prebiotic.


2021 ◽  
Vol 7 (12) ◽  
Author(s):  
Sophie Marre ◽  
Cyrielle Gasc ◽  
Camille Forest ◽  
Yacine Lebbaoui ◽  
Pascale Mosoni ◽  
...  

Targeting small parts of the 16S rDNA phylogenetic marker by metabarcoding reveals microorganisms of interest but cannot achieve a taxonomic resolution at the species level, precluding further precise characterizations. To identify species behind operational taxonomic units (OTUs) of interest, even in the rare biosphere, we developed an innovative strategy using gene capture by hybridization. From three OTU sequences detected upon polyphenol supplementation and belonging to the rare biosphere of the human gut microbiota, we revealed 59 nearly full-length 16S rRNA genes, highlighting high bacterial diversity hidden behind OTUs while evidencing novel taxa. Inside each OTU, revealed 16S rDNA sequences could be highly distant from each other with similarities down to 85 %. We identified one new family belonging to the order Clostridiales , 39 new genera and 52 novel species. Related bacteria potentially involved in polyphenol degradation have also been identified through genome mining and our results suggest that the human gut microbiota could be much more diverse than previously thought.


2014 ◽  
Vol 58 (8) ◽  
pp. 4535-4542 ◽  
Author(s):  
Usha Stiefel ◽  
Michelle M. Nerandzic ◽  
Michael J. Pultz ◽  
Curtis J. Donskey

ABSTRACTAntibiotics that are excreted into the intestinal tract may disrupt the indigenous intestinal microbiota and promote colonization by health care-associated pathogens. β-Lactam, or penicillin-type, antibiotics are among the most widely utilized antibiotics worldwide and may also adversely affect the microbiota. Many bacteria are capable, however, of producing β-lactamase enzymes that inactivate β-lactam antibiotics. We hypothesized that prior establishment of intestinal colonization with a β-lactamase-producing anaerobe might prevent these adverse effects of β-lactam antibiotics, by inactivating the portion of antibiotic that is excreted into the intestinal tract. Here, mice with a previously abolished microbiota received either oral normal saline or an oral cephalosporinase-producing strain ofBacteroides thetaiotaomicronfor 3 days. Mice then received 3 days of subcutaneous ceftriaxone, followed by either oral administration of vancomycin-resistantEnterococcus(VRE) or sacrifice and assessment ofin vitrogrowth of epidemic and nonepidemic strains ofClostridium difficilein murine cecal contents. Stool concentrations of VRE and ceftriaxone were measured, cecal levels ofC. difficile24 h after incubation were quantified, and denaturing gradient gel electrophoresis (DGGE) of microbial 16S rRNA genes was performed to evaluate the antibiotic effect on the microbiota. The results demonstrated that establishment of prior colonization with a β-lactamase-producing intestinal anaerobe inactivated intraintestinal ceftriaxone during treatment with this antibiotic, allowed recovery of the normal microbiota despite systemic ceftriaxone, and prevented overgrowth with VRE and epidemic and nonepidemic strains ofC. difficilein mice. These findings describe a novel probiotic strategy to potentially prevent pathogen colonization in hospitalized patients.


mBio ◽  
2014 ◽  
Vol 5 (3) ◽  
Author(s):  
Alyxandria M. Schubert ◽  
Mary A. M. Rogers ◽  
Cathrin Ring ◽  
Jill Mogle ◽  
Joseph P. Petrosino ◽  
...  

ABSTRACTAntibiotic usage is the most commonly cited risk factor for hospital-acquiredClostridium difficileinfections (CDI). The increased risk is due to disruption of the indigenous microbiome and a subsequent decrease in colonization resistance by the perturbed bacterial community; however, the specific changes in the microbiome that lead to increased risk are poorly understood. We developed statistical models that incorporated microbiome data with clinical and demographic data to better understand why individuals develop CDI. The 16S rRNA genes were sequenced from the feces of 338 individuals, including cases, diarrheal controls, and nondiarrheal controls. We modeled CDI and diarrheal status using multiple clinical variables, including age, antibiotic use, antacid use, and other known risk factors using logit regression. This base model was compared to models that incorporated microbiome data, using diversity metrics, community types, or specific bacterial populations, to identify characteristics of the microbiome associated with CDI susceptibility or resistance. The addition of microbiome data significantly improved our ability to distinguish CDI status when comparing cases or diarrheal controls to nondiarrheal controls. However, only when we assigned samples to community types was it possible to differentiate cases from diarrheal controls. Several bacterial species within theRuminococcaceae,Lachnospiraceae,Bacteroides, andPorphyromonadaceaewere largely absent in cases and highly associated with nondiarrheal controls. The improved discriminatory ability of our microbiome-based models confirms the theory that factors affecting the microbiome influence CDI.IMPORTANCEThe gut microbiome, composed of the trillions of bacteria residing in the gastrointestinal tract, is responsible for a number of critical functions within the host. These include digestion, immune system stimulation, and colonization resistance. The microbiome’s role in colonization resistance, which is the ability to prevent and limit pathogen colonization and growth, is key for protection againstClostridium difficileinfections. However, the bacteria that are important for colonization resistance have not yet been elucidated. Using statistical modeling techniques and different representations of the microbiome, we demonstrated that several community types and the loss of several bacterial populations, includingBacteroides,Lachnospiraceae, andRuminococcaceae, are associated with CDI. Our results emphasize the importance of considering the microbiome in mediating colonization resistance and may also direct the design of future multispecies probiotic therapies.


2018 ◽  
Vol 84 (18) ◽  
Author(s):  
Claudia Leong ◽  
Jillian J. Haszard ◽  
Blair Lawley ◽  
Anna Otal ◽  
Rachael W. Taylor ◽  
...  

ABSTRACT The introduction of “solids” (i.e., complementary foods) to the milk-only diet in early infancy affects the development of the gut microbiota. The aim of this study was to determine whether a “baby-led” approach to complementary feeding that encourages the early introduction of an adult-type diet results in alterations of the gut microbiota composition compared to traditional spoon-feeding. The Baby-Led Introduction to SolidS (BLISS) study randomized 206 infants to BLISS (a modified version of baby-led weaning [BLW], the introduction of solids at 6 months of age, followed by self-feeding of family foods) or control (traditional spoon-feeding of purées) groups. Fecal microbiotas and 3-day weighed-diet records were analyzed for a subset of 74 infants at 7 and 12 months of age. The composition of the microbiota was determined by sequencing of 16S rRNA genes amplified by PCR from bulk DNA extracted from feces. Diet records were used to estimate food and dietary fiber intake. Alpha diversity (number of operational taxonomic units [OTUs]) was significantly lower in BLISS infants at 12 months of age (difference [95% confidence interval {CI}] of 31 OTUs [3.4 to 58.5]; P = 0.028), and while there were no significant differences between control and BLISS infants in relative abundances of Bifidobacteriaceae, Enterobacteriaceae, Veillonellaceae, Bacteroidaceae, Erysipelotrichaceae, Lachnospiraceae, or Ruminococcaceae at 7 or 12 months of age, OTUs representing the genus Roseburia were less prevalent in BLISS microbiotas at 12 months. Mediation models demonstrated that the intake of “fruit and vegetables” and “dietary fiber” explained 29% and 25%, respectively, of the relationship between group (BLISS versus control) and alpha diversity. IMPORTANCE The introduction of solid foods (complementary feeding or weaning) to infants leads to more-complex compositions of microbial communities (microbiota or microbiome) in the gut. In baby-led weaning (BLW), infants are given only finger foods that they can pick up and feed themselves—there is no parental spoon-feeding of puréed baby foods—and infants are encouraged to eat family meals. BLW is a new approach to infant feeding that is increasing in popularity in the United States, New Zealand, the United Kingdom, and Canada. We used mediation modeling, commonly used in health research but not in microbiota studies until now, to identify particular dietary components that affected the development of the infant gut microbiota.


2015 ◽  
Vol 82 (4) ◽  
pp. 1256-1263 ◽  
Author(s):  
Aram Mikaelyan ◽  
Claire L. Thompson ◽  
Markus J. Hofer ◽  
Andreas Brune

ABSTRACTThe gut microbiota of termites plays important roles in the symbiotic digestion of lignocellulose. However, the factors shaping the microbial community structure remain poorly understood. Because termites cannot be raised under axenic conditions, we established the closely related cockroachShelfordella lateralisas a germ-free model to study microbial community assembly and host-microbe interactions. In this study, we determined the composition of the bacterial assemblages in cockroaches inoculated with the gut microbiota of termites and mice using pyrosequencing analysis of their 16S rRNA genes. Although the composition of the xenobiotic communities was influenced by the lineages present in the foreign inocula, their structure resembled that of conventional cockroaches. Bacterial taxa abundant in conventional cockroaches but rare in the foreign inocula, such asDysgonomonasandParabacteroidesspp., were selectively enriched in the xenobiotic communities. Donor-specific taxa, such as endomicrobia or spirochete lineages restricted to the gut microbiota of termites, however, either were unable to colonize germ-free cockroaches or formed only small populations. The exposure of xenobiotic cockroaches to conventional adults restored their normal microbiota, which indicated that autochthonous lineages outcompete foreign ones. Our results provide experimental proof that the assembly of a complex gut microbiota in insects is deterministic.


2014 ◽  
Vol 80 (17) ◽  
pp. 5254-5264 ◽  
Author(s):  
Ji-Hyun Yun ◽  
Seong Woon Roh ◽  
Tae Woong Whon ◽  
Mi-Ja Jung ◽  
Min-Soo Kim ◽  
...  

ABSTRACTInsects are the most abundant animals on Earth, and the microbiota within their guts play important roles by engaging in beneficial and pathological interactions with these hosts. In this study, we comprehensively characterized insect-associated gut bacteria of 305 individuals belonging to 218 species in 21 taxonomic orders, using 454 pyrosequencing of 16S rRNA genes. In total, 174,374 sequence reads were obtained, identifying 9,301 bacterial operational taxonomic units (OTUs) at the 3% distance level from all samples, with an average of 84.3 (±97.7) OTUs per sample. The insect gut microbiota were dominated byProteobacteria(62.1% of the total reads, including 14.1%Wolbachiasequences) andFirmicutes(20.7%). Significant differences were found in the relative abundances of anaerobes in insects and were classified according to the criteria of host environmental habitat, diet, developmental stage, and phylogeny. Gut bacterial diversity was significantly higher in omnivorous insects than in stenophagous (carnivorous and herbivorous) insects. This insect-order-spanning investigation of the gut microbiota provides insights into the relationships between insects and their gut bacterial communities.


2021 ◽  
Author(s):  
E. D. Baranova ◽  
V. G. Druzhinin ◽  
L. V. Matskova ◽  
P. S. Demenkov ◽  
V. P . Volobaev ◽  
...  

Abstract Recent findings indicate that the microbiome can have a significant impact on the development of lung cancer by inducing inflammatory responses, causing dysbiosis and generating genome damage. The aim of this study was to search for bacterial markers of squamous cell carcinoma (LUSC). In the study, the taxonomic composition of the sputum microbiome of 40 men with untreated LUSC was compared with 40 healthy controls. Next Generation sequencing of bacterial 16S rRNA genes was used to determine the taxonomic composition of the respiratory microbiome. There was no differences in alpha diversity between the LUSC and control groups. Meanwhile, differences in the structure of bacterial communities (β diversity) among patients and controls differed significantly in sputum samples (pseudo-F = 1.65; p = 0.026). Only Streptococcus, Bacillus, Gemella and Haemophilus were found to be significantly increased in patients with LUSC compared to the control subjects, while 19 bacterial genera were significantly reduced, indicating a decrease in beta diversity in the microbiome of patients with LUSC. From our study, Streptococcus (Streptococcus agalactiae) emerges as the most likely LUSC biomarker, but more research is needed to confirm this assumption.


2022 ◽  
Vol 25 (8) ◽  
pp. 864-873
Author(s):  
A. Y. Tikunov ◽  
A. N. Shvalov ◽  
V. V. Morozov ◽  
I. V. Babkin ◽  
G. V. Seledtsova ◽  
...  

To date, the association of an imbalance of the intestinal microbiota with various human diseases, including both diseases of the gastrointestinal tract and disorders of the immune system, has been shown. However, despite the huge amount of accumulated data, many key questions still remain unanswered. Given limited data on the composition of the gut microbiota in patients with ulcerative colitis (UC) and irritable bowel syndrome (IBS) from different parts of Siberia, as well as the lack of data on the gut microbiota of patients with bronchial asthma (BA), the aim of the study was to assess the biodiversity of the gut microbiota of patients with IBS, UC and BA in comparison with those of healthy volunteers (HV). In this study, a comparative assessment of the biodiversity and taxonomic structure of gut microbiome was conducted based on the sequencing of 16S rRNA genes obtained from fecal samples of patients with IBS, UC, BA and volunteers. Sequences of the Firmicutes and Bacteroidetes types dominated in all samples studied. The third most common in all samples were sequences of the Proteobacteria type, which contains pathogenic and opportunistic bacteria. Sequences of the Actinobacteria type were, on average, the fourth most common. The results showed the presence of dysbiosis in the samples from patients compared to the sample from HVs. The ratio of Firmicutes/Bacteroidetes was lower in the IBS and UC samples than in HV and higher the BA samples. In the samples from patients with intestinal diseases (IBS and UC), an increase in the proportion of sequences of the Bacteroidetes type and a decrease in the proportion of sequences of the Clostridia class, as well as the Ruminococcaceae, but not Erysipelotrichaceae family, were found. The IBS, UC, and BA samples had signif icantly more Proteobacteria sequences, including Methylobacterium, Sphingomonas, Parasutterella, Halomonas, Vibrio, as well as Escherichia spp. and Shigella spp. In the gut microbiota of adults with BA, a decrease in the proportion of Roseburia, Lachnospira, Veillonella sequences was detected, but the share of Faecalibacterium and Lactobacillus sequences was the same as in healthy individuals. A signif icant increase in the proportion of Halomonas and Vibrio sequences in the gut microbiota in patients with BA has been described for the f irst time.


2014 ◽  
Vol 64 (Pt_5) ◽  
pp. 1501-1506 ◽  
Author(s):  
Bacem Mnasri ◽  
Tian Yan Liu ◽  
Sabrine Saidi ◽  
Wen Feng Chen ◽  
Wen Xin Chen ◽  
...  

Three microbial strains isolated from common beans, 23C2T (Tunisia), Gr42 (Spain) and IE4868 (Mexico), which have been identified previously as representing a genomic group closely related to Rhizobium gallicum , are further studied here. Their 16S rRNA genes showed 98.5–99 % similarity with Rhizobium loessense CCBAU 7190BT, R. gallicum R602spT, Rhizobium mongolense USDA 1844T and Rhizobium yanglingense CCBAU 71623T. Phylogenetic analysis based on recA, atpD, dnaK and thrC sequences showed that the novel strains were closely related and could be distinguished from the four type strains of the closely related species. Strains 23C2T, Gr42 and IE4868 could be also differentiated from their closest phylogenetic neighbours by their phenotypic and physiological properties and their fatty acid contents. All three strains harboured symbiotic genes specific to biovar gallicum. Levels of DNA–DNA relatedness between strain 23C2T and the type strains of R. loessense , R. mongolense , R. gallicum and R. yanglingense ranged from 58.1 to 61.5 %. The DNA G+C content of the genomic DNA of strain 23C2T was 59.52 %. On the basis of these data, strains 23C2T, Gr42 and IE4868 were considered to represent a novel species of the genus Rhizobium for which the name Rhizobium azibense is proposed. Strain 23C2T ( = CCBAU 101087T = HAMBI3541T) was designated as the type strain.


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