scholarly journals Optimization of Conditions for Human Bacterial Preparation for Biological Correction of Intestinal Microflora

2021 ◽  
Vol 4 (2) ◽  
pp. e00151
Author(s):  
E.A. Sorokina ◽  
E.S. Zhgun ◽  
Yu.V. Kislun ◽  
E.A. Denisova ◽  
Yu.A. Bespyatykh ◽  
...  

Fecal microbiota transplantation (FMT) is now considered as an effective tool for the treatment of various GI pathologies. Fecal preparations are delivered both through the lower GIT (enema, colonoscopy) and upper (endoscopy, capsules). A common disadvantage of instrumental methods of administration is their high invasiveness associated with the risk of intestinal perforation and the use of anesthesia. Oral capsules are minimally invasive, comfortable and more aesthetic, so this method of drug delivery is gaining popularity. The main issue with the use of frozen feces (including the lyophilisate used in capsules) is its efficiency compared to the original material. During lyophilization, cells are exposed to stress factors such as low temperatures, water crystallization, osmotic stress, changes in pH, and dehydration. To reduce the likelihood of cell damage during lyophilization, protective media (lyo-protectants) are used. In this work sucrose, gelatin, and their combinations have been used as lyoprotectors. To estimate the number of microorganisms, a bacteriological study was carried out. The number of Bifidobacteria, Lactobacilli, and the total number of E.coli and Enterobacteriaceae was estimated. It was found that the lyophilized stool sample containing 10% sucrose as a protective medium had the highest number of viable cells. Also, the physical properties of the lyophilisate (its flowability) are convenient for preparing capsulated form. The molar ratios of short chain fatty acids (SCFAs) in the original fecal samples and lyophilisates were studied by gas chromatography. The molar ratios of major SCFAs (acetate, propionate and butyrate) were identical in the samples studied. The composition of the protective medium in which the lyophilized biomaterial corresponds to the original feces in terms of the number of "live" microorganisms has been proposed. According to its physical characteristics lyophilisate is convenient for capsules preparation.

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Markus M. Heimesaat ◽  
Katharina Mrazek ◽  
Stefan Bereswill

AbstractConventional mice are protected from Campylobacter jejuni infection by the murine host-specific gut microbiota composition. We here addressed whether peroral fecal microbiota transplantation (FMT) might be an antibiotics-independent option to lower even high gastrointestinal C. jejuni loads in the infected vertebrate host. To address this, secondary abiotic mice were generated by broad-spectrum antibiotic treatment and perorally infected with C. jejuni by gavage. One week later, mice were stably colonized with more than 109 C. jejuni and subjected to peroral FMT from murine donors on three consecutive days. Two weeks post-intervention, gastrointestinal C. jejuni loads were up to 7.5 orders of magnitude lower following murine FMT versus mock challenge. Remarkably, FMT reversed C. jejuni induced colonic epithelial apoptosis, but enhanced proliferative and regenerative responses in the colon thereby counteracting pathogenic cell damage. Furthermore, FMT dampened both, innate and adaptive immune cell responses in the large intestines upon C. jejuni infection that were accompanied by less C. jejuni-induced colonic nitric oxide secretion. Our study provides strong evidence that novel probiotic formulations developed as alternative option to FMT in severe intestinal inflammatory morbidities including Clostridoides difficile infection might be effective to treat campylobacteriosis and lower pathogen loads in colonized vertebrates including farm animals.


2019 ◽  
Vol 7 (1) ◽  
Author(s):  
Alessandra Oliva ◽  
Lucia Aversano ◽  
Massimiliano De Angelis ◽  
Maria Teresa Mascellino ◽  
Maria Claudia Miele ◽  
...  

Abstract Background Clostridioides difficile infection (CDI) might be complicated by the development of nosocomial bloodstream infection (n-BSI). Based on the hypothesis that alteration of the normal gut integrity is present during CDI, we evaluated markers of microbial translocation, inflammation, and intestinal damage in patients with CDI. Methods Patients with documented CDI were enrolled in the study. For each subject, plasma samples were collected at T0 and T1 (before and after CDI therapy, respectively), and the following markers were evaluated: lipopolysaccharide-binding protein (LPB), EndoCab IgM, interleukin-6, intestinal fatty acid binding protein (I-FABP). Samples from nonhospitalized healthy controls were also included. The study population was divided into BSI+/BSI- and fecal microbiota transplantation (FMT) +/FMT- groups, according to the development of n-BSI and the receipt of FMT, respectively. Results Overall, 45 subjects were included; 8 (17.7%) developed primary n-BSI. Markers of microbial translocation and intestinal damage significantly decreased between T0 and T1, however, without reaching values similar to controls (P < .0001). Compared with BSI-, a persistent high level of microbial translocation in the BSI+ group was observed. In the FMT+ group, markers of microbial translocation and inflammation at T1 tended to reach control values. Conclusions CDI is associated with high levels of microbial translocation, inflammation, and intestinal damage, which are still present at clinical resolution of CDI. The role of residual mucosal perturbation and persistence of intestinal cell damage in the development of n-BSI following CDI, as well as the possible effect of FMT in the restoration of mucosal integrity, should be further investigated.


2019 ◽  
Vol 97 (Supplement_3) ◽  
pp. 305-306
Author(s):  
Quanhang Xiang ◽  
Jian Peng

Abstract The objective of this study was to investigate the effects of early gut colonization by fecal microbiota transplantation and probiotics intervention on growth performance, immunity function, and gut health of piglets. A total of 121 pregnant sows were divided into 6 groups with average parity of 3.66 ± 1.34. After delivery, piglets of group AB were treated with antibiotics at age of 3-day. Piglets of group CON were gavaged with PBS. The remaining four treatment groups, FMT, FMT+C, FMT+S, and FMT+C+S, the piglets were gavaged with fecal suspension, fecal suspension with C. butyricum, fecal suspension with S. boulardii, and fecal suspension with C. butyricum and S.boulardii, respectively, with the frequency of once daily in the first 3 days. All the piglets were weaned at age of 21 day. The individual body weight of piglets were weighed weekly, blood samples and fecal samples were collected weekly. At the end of study, the ADG and diarrhea rate were caculated. FMT+C+S and FMT could increased piglets 21-day-old weight (P < 0.01), and FMT+C+S could increased ADG (P < 0.05) and decreased diarrhea rate (P < 0.05). Early antibiotics exposure for health care has no positive effect on growth performance and diarrhea. FMT, FMT+S and FMT+C+S improved fecal sIgA and plasma IgG of 14-day-old piglets (P < 0.05). FMT+C+S decreased the concentration of plasma DAO and D-LA, and increased fecal MUC2 content, so that the intestinal barrier was enhanced. The early intervention of FMT combined with C. butyricum and S. boulardii reduced the abundance of E. coli, and increased the abundance of Lactobacillus, Bifidobacterium and Faecalibacterium prausnitzii. In addition, it also increases the production of intestinal short-chain fatty acids. In conclusion, these data indicated that early intervention with FMT combined C. butyricum and S. boulardii could improve the growth performance, immune responses, and gut function of sucking piglets.


2020 ◽  
Vol 14 (10) ◽  
pp. 1074-1080
Author(s):  
Muluneh Ademe

A growing body of literatures showed the interaction of dysbiotic gut with a wide range of disorders, and the clinical use of fecal microbiota transplantation (FMT) shifted from infectious disease to non-communicable disorders. Despite the promising therapeutic benefits of FMT, the exact mechanisms through which fecal recipients benefit from the fecal intervention are not well understood. However, owing to the advantages of having a healthy gut microbiome, possible mechanisms of actions of FMT has been described. On the one hand, through direct ecological competition, FMT may potentially stimulate decolonization of pathogenic microorganisms and increase host resistance to pathogens. Moreover, following dysbiosis, abnormal microbial colonization of the gastrointestinal tract may also cause excessive or dysregulated immune response, resulting in chronic inflam­mation and the development of mucosal lesions. In this regard, repopulating gut microbiome through FMT helps to restore immune function and reduce host damage. On the other hand, FMT helps to restore essential metabolites used for host metabolism, including short-chain fatty acids (SCFA), antimicrobial peptides (AMP), bacteriocins and bile acids. Therefore, in this review, the existing evidences regarding the mechanisms of action, current opportunities and challenges of FMT will be described.


2020 ◽  
Author(s):  
Yingli Jing ◽  
Yan Yu ◽  
Fan Bai ◽  
Limiao Wang ◽  
Degang Yang ◽  
...  

Abstract Background: Spinal cord injury (SCI) patients display disruption of gut microbiome and gut dysbiosis exacerbate neurological impairment in SCI models. Cumulative data support an important role of gut microbiome in SCI. Here, we investigated the hypothesis that fecal microbiota transplantation (FMT) may exert a neuroprotective effect on SCI mice. Results: We found that FMT facilitated functional recovery, promoted neural axonal regeneration, improved animal weight gain and metabolic profiling, and enhanced intestinal barrier integrity and GI motility. High-throughput sequencing revealed that levels of phylum Firmicutes, genus Blautia, Anaerostipes and Lactobacillus were reduced in fecal samples of SCI mice, and FMT remarkably reshaped gut microbiome. Also, FMT-treated SCI mice showed increased amount of fecal short-chain fatty acids (SCFAs), which correlated with alteration of intestinal permeability and locomotor recovery. Furthermore, FMT down-regulated IL-1β/NF-κB signaling in spinal cord and NF-κB signaling in gut. Conclusion: Our study demonstrates that reprogramming of gut microbiota by FMT improves locomotor and GI functions in SCI mice, possibly through the anti-inflammatory functions of SCFAs.


2021 ◽  
Vol 12 ◽  
Author(s):  
Hao-Ming Xu ◽  
Hong-Li Huang ◽  
Jing Xu ◽  
Jie He ◽  
Chong Zhao ◽  
...  

Fecal microbiota transplantation (FMT) can inhibit the progression of ulcerative colitis (UC). However, how FMT modulates the gut microbiota and which biomarker is valuable for evaluating the efficacy of FMT have not been clarified. This study aimed to determine the changes in the gut microbiota and their relationship with butyric acid following FMT for UC. Fecal microbiota (FM) was isolated from healthy individuals or mice and transplanted into 12 UC patients or colitis mice induced by dextran sulfate sodium (DSS). Their clinical colitis severities were monitored. Their gut microbiota were analyzed by 16S sequencing and bioinformatics. The levels of fecal short-chain fatty acids (SCFAs) from five UC patients with recurrent symptoms after FMT and individual mice were quantified by liquid chromatography–mass spectrometry (LC–MS). The impact of butyric acid on the abundance and diversity of the gut microbiota was tested in vitro. The effect of the combination of butyric acid-producing bacterium and FMT on the clinical responses of 45 UC patients was retrospectively analyzed. Compared with that in the controls, the FMT significantly increased the abundance of butyric acid-producing bacteria and fecal butyric acid levels in UC patients. The FMT significantly increased the α-diversity, changed gut microbial structure, and elevated fecal butyric acid levels in colitis mice. Anaerobic culture with butyrate significantly increased the α-diversity of the gut microbiota from colitis mice and changed their structure. FMT combination with Clostridium butyricum-containing probiotics significantly prolonged the UC remission in the clinic. Therefore, fecal butyric acid level may be a biomarker for evaluating the efficacy of FMT for UC, and addition of butyrate-producing bacteria may prolong the therapeutic effect of FMT on UC by changing the gut microbiota.


Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3719
Author(s):  
Daniela Maria Tanase ◽  
Evelina Maria Gosav ◽  
Ecaterina Neculae ◽  
Claudia Florida Costea ◽  
Manuela Ciocoiu ◽  
...  

Type 2 diabetes mellitus (T2DM) remains one of the most problematic and economic consumer disorders worldwide, with growing prevalence and incidence. Over the last years, substantial research has highlighted the intricate relationship among gut microbiota, dysbiosis and metabolic syndromes development. Changes in the gut microbiome composition lead to an imbalanced gastrointestinal habitat which promotes abnormal production of metabolites, inflammatory status, glucose metabolism alteration and even insulin resistance (IR). Short-chain fatty acids (SCFAs), trimethylamine N-oxide (TMAO), lipopolysaccharide, aromatic amino acids and their affiliated metabolites, contribute to T2DM via different metabolic and immunologic pathways. In this narrative review, we discuss the immunopathogenic mechanism behind gut dysbiosis, T2DM development and the major known diabetic microvascular complications (retinopathy, neuropathy and nephropathy), the beneficial use of pre- and pro-biotics and fecal microbiota transplantation in T2DM management and new findings and future perspectives in this field.


2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Lili Zhang ◽  
Jinjin Chu ◽  
Wenhao Hao ◽  
Jiaojiao Zhang ◽  
Haibo Li ◽  
...  

Gut microbiota has attracted widespread attention due to its crucial role in disease pathophysiology, including type 2 diabetes mellitus (T2DM). Metabolites and bacterial components of gut microbiota affect the initiation and progression of T2DM by regulating inflammation, immunity, and metabolism. Short-chain fatty acids, secondary bile acid, imidazole propionate, branched-chain amino acids, and lipopolysaccharide are the main molecules related to T2DM. Many studies have investigated the role of gut microbiota in T2DM, particularly those butyrate-producing bacteria. Increasing evidence has demonstrated that fecal microbiota transplantation and probiotic capsules are useful strategies in preventing diabetes. In this review, we aim to elucidate the complex association between gut microbiota and T2DM inflammation, metabolism, and immune disorders, the underlying mechanisms, and translational applications of gut microbiota. This review will provide novel insight into developing individualized therapy for T2DM patients based on gut microbiota immunometabolism.


2017 ◽  
Author(s):  
Anna M. Seekatz ◽  
Casey M. Theriot ◽  
Krishna Rao ◽  
Yu-Ming Chang ◽  
Alison E. Freeman ◽  
...  

ABSTRACTA significant proportion of individuals develop recurrentClostridium difficileinfection (CDI) following initial disease. Fecal microbiota transplantation (FMT), a highly effective treatment method for recurrent CDI, has been demonstrated to induce microbiota recovery, a critical component of disease recovery. However, identification of the specific microbes and their functions that directly impact recovery from CDI remains difficult. We assessed for associations among microbial community members and metabolites in patients with recurrent CDI following treatment with FMT over time to identify groups of bacteria with potential restorative functions. Using 16S rRNA gene-based sequencing, we observed marked similarity of the microbiota between recipients following FMT (n = 6, sampling up to 6 months post-FMT) and their respective donors. Increased levels of the secondary bile acid deoxycholic acid and the short chain fatty acids (SCFAs) butyrate, acetate, and propionate were observed post-FMT. To take into account longitudinal sampling and intra-individual differences, we applied a generalized estimating equation approach to model metabolite concentrations with the presence of specific members of the microbiota. Microbial metabolites that were increased following FMT associated with members classified within theLachnospiraceae, Ruminococcaceae, and unclassifiedClostridialesfamilies. In contrast, members of these taxa were inversely associated with primary bile acids. The longitudinal aspect of this study allowed us to characterize individualized patterns of recovery, revealing variability between and within patients following FMT.IMPORTANCEClostridium difficileinfection (CDI) is an urgent and serious healthcare-associated problem. In recent years, fecal microbiota transplantation (FMT) has been successfully used to treat recurrent CDI, a frequent outcome of disease. While it is apparent that FMT promotes recovery of the microbiota, it is unclear how microbes and their functions promote recovery from disease. This study aimed to identify associations among microbes and metabolites following FMT and to identify critical microbial functions following FMT treatment for recurrent CDI. Overall, recovery of the metabolome was highly dynamic and individualized in all patients, who were all successfully treated. Our results suggest that microbial changes following FMT may be highly specific to the donor-recipient relationship. Further understanding of the host-microbe environments necessary to enable successful transplantation of microbes during FMT could aid development of specific microbial therapeutics for recurrent CDI and other gastrointestinal diseases.


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