Amelioration of depressive symptoms on Fawn-Hooded rats through the ‘healthy’ fecal microbiota transplantation

Abstract Gut microbiome dysbiosis is associated with the development of depression. Fecal microbiota transplantation (FMT) has been proposed as a potential therapeutic solution for depression. However, the efficacy of FMT to reduce depression is still unknown. We performed FMT from Sprague-Dawley (SD) rats (‘healthy’ controls) to Fawn-hooded (FH) rats (depression model). Pre-FMT, the FH rats exhibited significantly elevated depressive behaviors and distinct neurotransmitter and cytokine levels compared with SD rats. Post-FMT, FH recipients receiving SD microbiota showed reduced depressive behaviors, a significant increase in hippocampal neurotransmitters and a significant decrease of some hippocampal cytokines compared to the ones receiving FH microbiota. SD-FMT resulted in the FH recipients’ gut microbiome resembling the SD donor; additionally, FH recipients showed a significant shift in the serum metabolome, but not the hippocampal metabolome. Co-occurrence analysis suggests that SD-FMT ameliorated recipients’ physiochemical features of depression by the metabolic modulation through the enteric nervous system, the intestinal barrier and the blood-brain barrier. Our results provided new data pointing to multiple mechanisms of interaction for the impact of gut microbiome modulation on depression.

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Amelioration of depressive symptoms on Fawn-Hooded rats through the 'healthy' fecal microbiota transplantation

10.21203/rs.3.rs-917357/v2 ◽

2021 ◽

Author(s):

Bing Hu ◽

Promi Das ◽

Xianglin Lv ◽

Meng Shi ◽

Jiye Aa ◽

...

Keyword(s):

Gut Microbiome ◽

Fecal Microbiota Transplantation ◽

Intestinal Barrier ◽

Fecal Microbiota ◽

Significant Shift ◽

Healthy Controls ◽

Sprague Dawley ◽

Sd Rats ◽

Cytokine Levels ◽

The Impact

Abstract Background : Depression is a recurrent, heterogeneous mood disorder, occurring in more than 260 million people worldwide. Gut microbiome dysbiosis is associated with the development of depressive-like behaviors by modulating neuro-biochemical metabolism through the microbiome-gut-brain (MGB) axis. Fecal microbiota transplantation (FMT) has been proposed as a potential therapeutic solution for depression, but the therapeutic efficiency and mechanism is unknown. Results : We performed FMT from Sprague-Dawley (SD) rats ('healthy' controls) to Fawn-hooded (FH) rats (depression model). Pre-FMT, the FH rats exhibited significantly elevated depressive behaviors and distinct neurotransmitter and cytokine levels compared with SD rats. Post-FMT, FH recipients receiving SD microbiota showed reduced depressive behaviors, a significant increase in hippocampal neurotransmitters and a significant decrease of some hippocampal cytokines compared to the ones receiving FH microbiota. SD-FMT resulted in the FH recipients' gut microbiome resembling the SD donor, and a significant shift in the serum metabolome but not the hippocampal metabolome. Conclusions : SD-FMT was inferred to ameliorate recipients' physiochemical features of depression via the significant decrease of gut microbial species such as Dialister sp., which led to the recipients' metabolic modulation in serum and hippocampus through the enteric nervous system, the intestinal barrier and the blood-brain barrier. Our results provided new data pointing to multiple mechanisms of interaction for the impact of gut microbiome modulation on depression therapy.

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

Biomedicines ◽

10.3390/biomedicines9020145 ◽

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).

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

10.21203/rs.3.rs-20108/v1 ◽

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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The effect of Sennoside A on the improvement of lipopolysaccharide -associated encephalopathy through gut microbiota

10.21203/rs.3.rs-201567/v1 ◽

2021 ◽

Author(s):

Suyan Li ◽

Fenyan Zhang ◽

Yiguang Lin ◽

Xiaoli Niu ◽

Jian Lv ◽

...

Keyword(s):

Gut Microbiota ◽

Fecal Microbiota Transplantation ◽

Intestinal Flora ◽

Fecal Microbiota ◽

Protective Effects ◽

Sprague Dawley ◽

Microbial Composition ◽

Germ Free ◽

Sd Rats ◽

Tnf Α

Abstract Background Accumulating evidence suggests that the intestinal flora is involved in many neurodegenerative diseases. Sepsis can lead to severe intestinal flora imbalance and brain dysfunction. In this study, we investigated Sennoside A may relieve lipopolysaccharide(LPS)-associated encephalopathy via its effect on the gut microbiota in rats. Methods Adult male Sprague-Dawley (SD) rats and germ free (GF) rats were used. The ordinary and germ free SD rats were adopted as a LPS-associated encephalopathy model with or without Sennoside A administration. We investigated gut microbiota diversity and structure, conducted electroencephalograms (EEG) and measured the levels of TNF-α, IL-1β and IL-6 in the cortexes of Sprague Dawley (SD) rats with or without Sennoside A administration. Horizontal fecal microbiota transplantation (FMT) and germ-free rats were used to confirm the important roles of gut microbiota in the mitigation of LPS-associated encephalopathy in rats after Sennoside A supplementation. Results We found that Sennoside A treatment markedly improved brain function in septic rats including decreased ratios of abnormal EEG and lowered levels of TNF-α, IL-1β, and IL-6 in the rat cortexes. While the gut microbiota changed in septic SD rats, Sennoside A improved gut microbial composition, which might mediate its brain protective effects in sepsis. Sennoside A also reduced inflammation in the cortexes of septic rats via gut microbiota improvement. In germ-free rats that received lipopolysaccharide(LPS),Sennoside A could not lower the ratios of abnormal EEG, and could not alleviate TNF-α, IL-1β, and IL-6 levels in the rats’ cortexes. FMT lowered the ratios of abnormal EEG and alleviate TNF-α, IL-1β, and IL-6 levels in rats’ cortexes, which confirmed our hypothesis that the effect of Sennoside A on the improvement of LPS-associated encephalopathy through gut microbiota. Conclusion Our data confirm our hypothesis that Sennoside A likely exerts its brain protective effects through gut microbiota alteration.

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

Microbiome ◽

10.1186/s40168-021-01007-y ◽

2021 ◽

Vol 9 (1) ◽

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) from healthy uninjured mice into SCI mice may exert a neuroprotective effect. Results FMT facilitated functional recovery, promoted neuronal axonal regeneration, improved animal weight gain and metabolic profiling, and enhanced intestinal barrier integrity and GI motility in SCI mice. High-throughput sequencing revealed that levels of phylum Firmicutes, family Christensenellaceae, and genus Butyricimonas 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 downregulated IL-1β/NF-κB signaling in spinal cord and NF-κB signaling in gut following SCI. 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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Lupus Gut Microbiota Transplants Cause Autoimmunity and Inflammation

10.1101/2021.08.15.456375 ◽

2021 ◽

Author(s):

Yiyangzi Ma ◽

Ruru Guo ◽

Yiduo Sun ◽

Xin Li ◽

Lun He ◽

...

Keyword(s):

Gut Microbiota ◽

Lupus Erythematosus ◽

Fecal Microbiota Transplantation ◽

Fecal Microbiota ◽

Healthy Controls ◽

Germ Free ◽

Autoimmune Antibodies ◽

Expression Of Genes ◽

Rdna Sequencing

Background: The etiology of systemic lupus erythematosus (SLE) is multifactorial. Recently, growing evidence suggests that the microbiota plays a role in SLE, yet whether gut microbiota participates in the development of SLE remains largely unknown. To investigate this issue, we carried out 16s rDNA sequencing analyses in a cohort of 18 female un-treated active SLE patients and 7 female healthy controls, and performed fecal microbiota transplantation from patients and healthy controls to germ-free mice. Results: Compared to the healthy controls, we found no significant different microbial diversity but some significantly different species in SLE patients including Turicibacter genus and other 5 species. Fecal transfer from SLE patients to germ free (GF) C57BL/6 mice caused GF mice to develop a series of lupus-like phenotyptic features, which including an increased serum autoimmune antibodies, and imbalanced cytokines, altered distribution of immune cells in mucosal and peripheral immune response, and upregulated expression of genes related to SLE in recipient mice that received SLE fecal microbiota transplantation (FMT). Moreover, the metabolism of histidine was significantly altered in GF mice treated with SLE patient feces, as compared to those which received healthy fecal transplants. Conclusions: Overall, our results describe a causal role of aberrant gut microbiota in contributing to the pathogenesis of SLE. The interplay of gut microbial and histidine metabolism may be one of the mechanisms intertwined with autoimmune activation in SLE.

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A theoretical model of temperate phages as mediators of gut microbiome dysbiosis

F1000Research ◽

10.12688/f1000research.18480.1 ◽

2019 ◽

Vol 8 ◽

pp. 997 ◽

Cited By ~ 1

Author(s):

Derek M. Lin ◽

Henry C. Lin

Keyword(s):

Colorectal Cancer ◽

Inflammatory Bowel Disease ◽

Bacterial Community ◽

Gut Microbiome ◽

Fecal Microbiota Transplantation ◽

Fecal Microbiota ◽

Functional Changes ◽

Inflammatory Bowel ◽

Insight Into

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.

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Fecal microbiota transplantation increases colonic IL-25 and dampens tissue inflammation in patients with recurrent Clostridioides difficile

10.1101/2021.07.16.21260643 ◽

2021 ◽

Author(s):

Ning-Jiun Jan ◽

Noah Oakland ◽

Pankaj Kumar ◽

Girija Ramakrishnan ◽

Brian W. Behm ◽

...

Keyword(s):

Mononuclear Cells ◽

Fecal Microbiota Transplantation ◽

Alpha Diversity ◽

The United States ◽

Fecal Microbiota ◽

Peripheral Blood Mononuclear ◽

Clostridioides Difficile ◽

Rdna Sequencing ◽

Clostridioides Difficile Infection ◽

The Impact

Background: Clostridioides difficile infection (CDI) is the most common hospital-acquired infection in the United States. Antibiotic-induced dysbiosis is the primary cause of susceptibility and fecal microbiota transplantation (FMT) has emerged as an effective therapy for recurrence. We previously demonstrated in the mouse model of CDI that antibiotic-induced dysbiosis reduced colonic expression of IL-25, and that FMT protected in part by restoring gut commensal bacteria-mediated IL-25 signaling. Here we conducted a prospective clinical trial to test the impact of FMT on immunity, specifically testing in humans if FMT induced IL-25 expression in the colon. Methods: Subjects received colonic biopsies and blood sampling at the time of FMT and 60-days later. Colon biopsies were assayed for IL-25 by immunoassay, for mRNA by RNAseq, and for bacterial content by 16 S rDNA sequencing. High dimensional flow cytometry was also conducted on peripheral blood mononuclear cells pre- and post-FMT. Results: All 10 subjects who received FMT had no CDI recurrences over a 2 year follow-up post FMT. FMT increased alpha diversity of the colonic microbiota and was associated with several immunologic changes. The cytokine IL-25 was increased in colonic tissue. In addition, increased expression of homeostatic genes and repression of inflammatory genes was observed in colonic mRNA transcripts. Finally, circulating Th17 cells were decreased post-FMT. Conclusion: The increase in the cytokine IL-25 accompanied by decreased inflammation is consistent with FMT acting in part to protect from recurrent CDI via restoration of commensal activation of type 2 immunity.

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Extended Screening Costs Associated With Selecting Donors for Fecal Microbiota Transplantation for Treatment of Metabolic Syndrome-Associated Diseases

Open Forum Infectious Diseases ◽

10.1093/ofid/ofx243 ◽

2017 ◽

Vol 4 (4) ◽

Cited By ~ 17

Author(s):

Laura J Craven ◽

Seema Nair Parvathy ◽

Justin Tat-Ko ◽

Jeremy P Burton ◽

Michael S Silverman

Keyword(s):

Metabolic Syndrome ◽

Fecal Microbiota Transplantation ◽

The United States ◽

Fecal Microbiota ◽

Screening Programs ◽

Central Processing ◽

Donor Screening ◽

Increased Risk ◽

The Cost ◽

The Impact

Abstract Background Knowledge of the impact of the gut microbiome on conditions other than Clostridium difficile infection has been rapidly increasing, and the potential usefulness of fecal microbiota transplantation (FMT) in these indications is being explored. The need to exclude donors with an increased risk of these diseases has left uncertainties regarding the cost and feasibility of donor screening. The aim of this study was to compare our experience to other donor-screening programs and report the costs associated with establishing a donor-screening program, for the treatment of metabolic syndrome-related conditions. Methods Forty-six potential donors (PDs) had their medical histories and physical examinations undertaken by a physician. Blood, stool, and urine were screened for 31 viral, bacterial, fungal, and protozoan agents in addition to biochemical characteristics. The price of advertising, doctor’s visits and diagnostic tests were calculated to determine the cost of finding a donor. Results Of the PDs screened, 5 of 46 passed the history, examination, blood, stool, and urine tests. The most common reasons for exclusion included a body mass index >25 or the detection of Blastocystis hominis, Dientamoeba fragilis, or Helicobacter pylori. Four of five eligible donors had subsequent travel or illness that contraindicated donation, so only 1 of 46 PDs was suitable. The total cost for finding a single suitable donor was $15190 US dollars. This screening was performed in Canada, and costs in the United States would be substantially higher. Conclusions New potential therapeutic uses for FMT have created a demand for stricter exclusion criteria for donors. This study illustrates that screening many individuals to find a donor and the subsequent associated costs may make central processing and shipment a more reasonable alternative.

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