scholarly journals Fecal Microbiota Transplantation as a Tool for Therapeutic Modulation of Non-gastrointestinal Disorders

2021 ◽  
Vol 8 ◽  
Author(s):  
Robert Liptak ◽  
Barbora Gromova ◽  
Roman Gardlik
Keyword(s):  
Clinical Studies ◽  
Molecular Mechanisms ◽  
Fecal Microbiota Transplantation ◽  
Short Chain Fatty Acids ◽  
Fecal Microbiota ◽  
Gastrointestinal Disorders ◽  
Therapeutic Tool ◽  
Alcoholic Fatty Liver ◽  
Animal Models Of Disease ◽  
Microbial Dysbiosis

Fecal microbiota transplantation has been primarily investigated as a therapeutic tool for a number of gut disorders. Optimistic results from clinical studies on Clostridium difficile infection, inflammatory bowel disease and irritable bowel syndrome have stimulated the expansion of possible indications in which FMT might represent a game changing approach. Microbial dysbiosis was shown in a number of non-gastrointestinal disorders. Moreover, FMT was proven to be effective in therapy of numerous animal models of disease. However, only a proportion of these disorders have been addressed in clinical studies using FMT. These include obesity, non-alcoholic fatty liver disease, cardiovascular inflammation and neurological disorders such as autism, depression and Parkinson's disease. Results from preclinical and clinical studies also outlined possible molecular mechanisms that contribute to alleviation of the disease. These range from increasing the circulating levels of microbial metabolites (trimethylamine N-oxide, lipopolysaccharide, short chain fatty acids) to stimulation of the enteric nervous system. Several methodological shortcomings are still to be addressed; however, positive results of the clinical studies indicate that further investigation of FMT as a therapeutic tool for non-gastrointestinal disorders can be expected in upcoming years.

scholarly journals Insights into the Impact of Microbiota in the Treatment of NAFLD/NASH and Its Potential as a Biomarker for Prognosis and Diagnosis

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 145
Author(s):  
Julio Plaza-Díaz ◽  
Patricio Solis-Urra ◽  
Jerónimo Aragón-Vela ◽  
Fernando Rodríguez-Rodríguez ◽  
Jorge Olivares-Arancibia ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Fecal Microbiota Transplantation ◽  
Liver Steatosis ◽  
Intestinal Barrier ◽  
Fecal Microbiota ◽  
Current Treatment ◽  
Immune Defense ◽  
Alcoholic Fatty Liver ◽  
The Impact

Non-alcoholic fatty liver disease (NAFLD) is an increasing cause of chronic liver illness associated with obesity and metabolic disorders, such as hypertension, dyslipidemia, or type 2 diabetes mellitus. A more severe type of NAFLD, non-alcoholic steatohepatitis (NASH), is considered an ongoing global health threat and dramatically increases the risks of cirrhosis, liver failure, and hepatocellular carcinoma. Several reports have demonstrated that liver steatosis is associated with the elevation of certain clinical and biochemical markers but with low predictive potential. In addition, current imaging methods are inaccurate and inadequate for quantification of liver steatosis and do not distinguish clearly between the microvesicular and the macrovesicular types. On the other hand, an unhealthy status usually presents an altered gut microbiota, associated with the loss of its functions. Indeed, NAFLD pathophysiology has been linked to lower microbial diversity and a weakened intestinal barrier, exposing the host to bacterial components and stimulating pathways of immune defense and inflammation via toll-like receptor signaling. Moreover, this activation of inflammation in hepatocytes induces progression from simple steatosis to NASH. In the present review, we aim to: (a) summarize studies on both human and animals addressed to determine the impact of alterations in gut microbiota in NASH; (b) evaluate the potential role of such alterations as biomarkers for prognosis and diagnosis of this disorder; and (c) discuss the involvement of microbiota in the current treatment for NAFLD/NASH (i.e., bariatric surgery, physical exercise and lifestyle, diet, probiotics and prebiotics, and fecal microbiota transplantation).

Non-uinform gut microbiota alteration patterns associated with therapeutic outcomes in an Alzheimer's disease animal model

2019 ◽  
Author(s):  
Min Wang ◽  
William Kwame Amakye ◽  
Jianing Cao ◽  
Congcong Gong ◽  
Xiaoyu Sun ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Gut Microbiota ◽  
Molecular Mechanisms ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Therapeutic Outcomes ◽  
Targeted Treatments ◽  
Amyloid Aβ

Abstract Background: Dysbiosis of gut microbiota is associated with the progression of beta-amyloid (Aβ) pathology in Alzheimer’s disease (AD). We aimed to identify uniform Aβ-responsible gut microbiota status as possible guideline for gut microbiota manipulation and the prediction of outcomes of microbiota targeted treatments. Six months old APP/PS1 mice from the same genetic background, housing and feeding conditions were then daily gavage with Metformin, peptides WN5 or PW5 to manipulate the gut microbiota for 12 weeks. Aβ pathology and gut microbiota were then explored and compared. Results: Fecal microbiota transplantation (FMT) from a 16 month old APP/PS1 mouse reconstituted the gut microbiota towards the donor and increased Aβ pathology in APP/PS1 mouse model. Metformin, peptides WN5 and PW5 all attenuated Aβ-plaque formation in APP/PS1 mouse model but each was associated with distinct gut microbiota status. No uniform gut microbiota pattern associated with Aβ pathology was found among different gut microbiota-targeted treatments. Conclusion: We found no uniform gut microbiota status associated with Aβ pathology suggesting gut microbiota status is not a suitable biomarker for AD diagnosis and treatment predictions. Alteration of gut microbiota in itself may not be sufficiently directly related to functional outcomes and might only be a shadow of deeper molecular mechanisms not fully understood. The findings here strongly suggested that the significance of gut microbiota alteration in disease pathology and treatment may have so far been over claimed and that interpretation of gut microbiota data should be done with utmost caution.

scholarly journals Intestinal microbiome and NAFLD: molecular insights and therapeutic perspectives

2019 ◽  
Vol 55 (2) ◽  
pp. 142-158 ◽  
Author(s):  
Haiming Hu ◽  
Aizhen Lin ◽  
Mingwang Kong ◽  
Xiaowei Yao ◽  
Mingzhu Yin ◽  
...  
Keyword(s):  
Liver Diseases ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Farnesoid X Receptor ◽  
Intestinal Microbiome ◽  
High Morbidity ◽  
Alcoholic Fatty Liver ◽  
Intestinal Microbes ◽  
Bile Acid Sequestrants ◽  
Alcoholic Fatty Liver Disease

AbstractNon-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of dysregulated lipid and glucose metabolism, which is often associated with obesity, dyslipidemia and insulin resistance. In view of the high morbidity and health risks of NAFLD, the lack of effective cure has drawn great attention. In recent years, a line of evidence has suggested a close linkage between the intestine and liver diseases such as NAFLD. We summarized the composition and characteristics of intestinal microbes and reviewed molecular insights into the intestinal microbiome in development and progression of NAFLD. Intestinal microbes mainly include bacteria, archaea, viruses and fungi, and the crosstalk between non-bacterial intestinal microbes and human liver diseases should be paid more attention. Intestinal microbiota imbalance may not only increase the intestinal permeability to gut microbes but also lead to liver exposure to harmful substances that promote hepatic lipogenesis and fibrosis. Furthermore, we focused on reviewing the latest “gut–liver axis”-targeting treatment, including the application of antibiotics, probiotics, prebiotics, synbiotics, farnesoid X receptor agonists, bile acid sequestrants, gut-derived hormones, adsorbents and fecal microbiota transplantation for NAFLD. In this review, we also discussed the potential mechanisms of “gut–liver axis” manipulation and efficacy of these therapeutic strategies for NAFLD treatment.

scholarly journals PSVIII-10 Effects of early intervention by fecal microbiota transplantation combined probiotics on the growth performance, intestinal barrier and immunity function, and gut microbiota in sucking piglets

2019 ◽  
Vol 97 (Supplement_3) ◽  
pp. 305-306
Author(s):  
Quanhang Xiang ◽  
Jian Peng
Keyword(s):  
Early Intervention ◽  
Growth Performance ◽  
Fecal Microbiota Transplantation ◽  
Intestinal Barrier ◽  
Short Chain Fatty Acids ◽  
Fecal Microbiota ◽  
Gut Health ◽  
Gut Colonization ◽  
Fecal Suspension ◽  
Immunity Function

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.

Occurence of initiation and progression of colorectal cancer in the changed intestinal environment.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 416-416
Author(s):  
Seiji Ohigashi ◽  
Kazuki Sudo ◽  
Daiki Kobayashi ◽  
Osamu Takahashi ◽  
Takuya Takahashi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Organic Acids ◽  
Organic Acid ◽  
High Performance ◽  
Short Chain Fatty Acids ◽  
Fecal Microbiota ◽  
Intestinal Environment ◽  
Microbial Dysbiosis ◽  
Fecal Ph ◽  
N 93

416 Background: Use of new molecular biology–based methods of bacterial identification is expected to help elucidate the relationship between colorectal cancer (CRC) and intestinal microbiota. However, it remains unclear whether microbial dysbiosis is the cause or the result of CRC onset. We analyzed the intestinal environments to determine whether the changes differed with the stage of CRC or adenoma. Methods: We analyzed fecal microbiota, organic acid concentrations, and pH in CRC patients (n=93), individuals with adenoma (n=23), and individuals with normal intestinal tracts (n=27). After patient hospitalization, the feces of all subjects were collected before any administration of laxatives or antibiotics to prepare the bowel.Thirteen bacterial groups were enumerated in the fecal microbiota by using reverse transcription–quantitative PCR (RT-qPCR). Eight kinds of organic acid were quantified using high-performance liquid chromatography, and fecal pH was measured by pH meter. Results: The counts of total bacteria (10.3 ± 0.7 vs. 10.8 ± 0.3 log10 cells/g of feces; p<0.001), 5 groups of obligate anaerobe (Clostridium coccoides group, C. leptum subgroup, Bacteroides fragilis group, Bifidobacterium, and Atopobium cluster), and 2 groups of facultative anaerobes (Enterobacteriaceae and Staphylococcus) were significantly lower in the CRC group than in the healthy individuals. While the concentrations of organic acids—particularly short chain fatty acids (SCFAs) such as acetic acid, propionic acid, and butyric acid—were significantly decreased in the CRC group, the pH was increased in the CRC group (7.4 ± 0.8 vs. 6.9 ± 0.6; p<0.001). Comparison among the CRC, adenoma, and non-adenoma groups revealed that fecal SCFAs concentrations and pH in the adenoma group were intermediate to the CRC group and the non-adenoma group. Within the CRC group, no differences in microbiota or organic acids were observed among T-stages or Dukes stages. Conclusions: CRC patients showed significant differences in the intestinal environment, including alterations of microbiota, decreased SCFAs, and elevated pH. These changes are not a result of CRC progression but are involved in CRC onset.

scholarly journals Benefits of fecal microbiota transplantation: A comprehensive review

2020 ◽  
Vol 14 (10) ◽  
pp. 1074-1080
Author(s):  
Muluneh Ademe
Keyword(s):  
Gut Microbiome ◽  
Fecal Microbiota Transplantation ◽  
Short Chain Fatty Acids ◽  
Fecal Microbiota ◽  
Microbial Colonization ◽  
Action Current ◽  
Therapeutic Benefits ◽  
Wide Range ◽  
The One ◽  
Host Metabolism

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.

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 ◽  
...  
Keyword(s):  
Fecal Microbiota Transplantation ◽  
Cell Damage ◽  
Short Chain Fatty Acids ◽  
Fecal Microbiota ◽  
Stress Factors ◽  
Original Material ◽  
Bacteriological Study ◽  
Molar Ratios ◽  
Stress Changes ◽  
Protective Medium

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.

scholarly journals Effect of fecal microbiota transplantation on neurological restoration in a spinal cord injury mouse model: involvement of brain-gut axis

2020 ◽  
Author(s):  
Yingli Jing ◽  
Yan Yu ◽  
Fan Bai ◽  
Limiao Wang ◽  
Degang Yang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Gut Microbiome ◽  
High Throughput Sequencing ◽  
Fecal Microbiota Transplantation ◽  
Neuroprotective Effect ◽  
Intestinal Barrier ◽  
Short Chain Fatty Acids ◽  
Fecal Microbiota ◽  
Cord Injury

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.

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