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Brain Sciences Jul 2023Vascular dementia is a type of dementia from brain damage caused by cerebrovascular lesions and vascular risk factors. is a species of , belonging to the category of...
Vascular dementia is a type of dementia from brain damage caused by cerebrovascular lesions and vascular risk factors. is a species of , belonging to the category of obligate anaerobe. The purpose of our work was to study the protection of on cognitive function in rats subjected to vascular dementia (VaD) and investigate underlying molecular mechanisms. The rats were randomly divided into three groups: control group, 2VO group and 2VO + group. The VaD rats (the 2VO group and 2VO + group) were generated by bilateral common carotid artery occlusion (2VO). Rats in the 2VO+ group were administered with twice daily. In comparison with the rats in the 2VO group, rats in the 2VO + group presented an enhanced cognitive ability, increased synapse-associated protein expression, a downregulation of proinflammatory factors and an upregulation of neurotrophic factors. The relevant mechanism of the protective effect of may be associated with the inhibition of glial cell-associated inflammation by regulating phosphorylation of CaMKII. In conclusion, attenuates neurological impairments via regulating synapse-associated protein expression and the liberation of inflammatory elements in vascular dementia rats. The findings above might benefit the development of transplantation as a promising treatment of VaD.
PubMed: 37626492
DOI: 10.3390/brainsci13081136 -
Frontiers in Immunology 2021Bacterial therapeutics are the emergent alternatives in treating autoimmune diseases such as Rheumatoid Arthritis [RA]. MCI 001 is one such therapeutic bacterium that...
Bacterial therapeutics are the emergent alternatives in treating autoimmune diseases such as Rheumatoid Arthritis [RA]. MCI 001 is one such therapeutic bacterium that has been proven to treat autoimmune diseases such as RA and multiple sclerosis [MS] in animal models. The present study characterized MCI 001 isolated from a human duodenal biopsy, and evaluated its impact on the gut microbial and metabolic profile in a longitudinal study using the collagen-induced arthritis model in HLA-DQ8.AEo transgenic mice. MCI 001 though closely related to the type strain of , DSM 19854, differed in utilizing glycerol. In culture, MCI 001 produced vitamins such as biotin and folate, and was involved in digesting complex carbohydrates and production of acetate. Colonization study showed that duodenum was the predominant niche for the gavaged MCI 001. A longitudinal follow-up of gut microbial profile in arthritic mice treated with MCI 001 suggested that dysbiosis caused due to arthritis was partially restored to the profile of naïve mice after treatment. A taxon-level analysis suggested an expansion of intestinal genus in MCI001 treated arthritic mice. Eubiosis achieved post treatment with MCI 001 was also reflected in the increased production of short-chain fatty acids [SCFAs]. Present study suggests that the treatment with MCI 001 leads to an expansion of by increasing the availability of simple carbohydrates and acetate. Restoration of microbial profile and metabolites like butyrate induce immune and gut homeostasis.
Topics: Adaptation, Physiological; Animals; Arthritis, Rheumatoid; Bile Acids and Salts; Biological Therapy; Butyrates; Disease Models, Animal; Fatty Acids, Volatile; Gastric Juice; Gastrointestinal Microbiome; Humans; Hydrogen-Ion Concentration; Mice; Mice, Transgenic; Prevotella; Symbiosis
PubMed: 34017324
DOI: 10.3389/fimmu.2021.609644 -
Expert Review of Neurotherapeutics Jan 2019: The gut microbiome helps to maintain a person's healthy state while perturbations in its function often leading to the development of inflammatory diseases including... (Review)
Review
: The gut microbiome helps to maintain a person's healthy state while perturbations in its function often leading to the development of inflammatory diseases including multiple sclerosis (MS). Consequently, gut-commensals which restore homeostasis have the potential to become novel therapeutic options for treating MS. MS patients have presented gut dysbiosis with a reduction in bacteria belonging to the genus. Notably, increased levels of are observed when disease-modifying therapies are used. Additionally, , an anaerobic bacterium derived from the human, can suppress disease in mice with experimental autoimmune encephalomyelitis, a preclinical MS model. : This review compares MS microbiome studies from different geographical regions to identify common gut bacteria. Literature on the potential use of as a therapy for MS and the next steps for developing microbial monotherapies in MS is also discussed. : Recent findings presenting an inverse correlation between and MS disease severity and ability of to suppress disease in preclinical models suggest that might provide an additional treatment option for MS patients. However, rigorous testing in well-designed control trials should be performed to determine the safety and efficacy in MS patients.
Topics: Animals; Dysbiosis; Gastrointestinal Microbiome; Humans; Multiple Sclerosis; Prevotella; Probiotics
PubMed: 30513004
DOI: 10.1080/14737175.2019.1555473 -
BMC Complementary Medicine and Therapies Apr 2023Ethanol-induced gastric mucosal lesions (EGML) is one of the most common digestive disorders for which current therapies have limited outcomes in clinical practice....
BACKGROUND
Ethanol-induced gastric mucosal lesions (EGML) is one of the most common digestive disorders for which current therapies have limited outcomes in clinical practice. Prevotella histicola (P. histicola) has shown probiotic efficacy against arthritis, multiple sclerosis and oestrogen deficiency-induced depression in mice; however, its role in EGML remains unclear in spite of its extensive colonisation of the stomach. Ferroptosis, which is characterised by lipid peroxidation, may be involved in EGML. Herein, we aimed to investigate the effects and underlying mechanism of action of P. histicola on EGML in the ferroptosis-dependent pathway.
METHODS
P. histicola was intragastrically administered for a week, and deferoxamine (DFO), a ferroptosis inhibitor, was intraperitoneally injected prior to oral ethanol administration. The gastric mucosal lesions and ferroptosis were assessed via histopathological examinations, quantitative real-time PCR, Western blot, immunohistochemistry and immunofluorescence.
RESULTS
P. histicola was originally found to attenuate EGML by reducing histopathological changes and lipid reactive oxygen species (ROS) accumulation. The pro-ferroptotic genes of Transferrin Receptor (TFR1), Solute Carrier Family 39 Member 14 (SLC39A14), Haem Oxygenase-1 (HMOX-1), Acyl-CoA Synthetase Long-chain Family Member 4 (ACSL4), Cyclooxygenase 2 (COX-2) and mitochondrial Voltage-dependent Anion Channels (VDACs) were up-regulated; the anti-ferroptotic System Xc-/Glutathione Peroxidase 4 (GPX4) axis was inhibited after ethanol administration. However, the changes of histopathology and ferroptosis-related parameters induced by ethanol were reversed by DFO. Furthermore, P. histicola treatment significantly downregulated the expression of ACSL4, HMOX-1 and COX-2, as well as TFR1 and SLC39A14, on mRNA or the protein level, while activating the System Xc-/GPX4 axis.
CONCLUSIONS
We found that P. histicola reduces ferroptosis to attenuate EGML by inhibiting the ACSL4- and VDAC-dependent pro-ferroptotic pathways and activating the anti-ferroptotic System Xc-/GPX4 axis.
Topics: Animals; Mice; Cyclooxygenase 2; Ferroptosis; Administration, Oral; Ethanol; Cation Transport Proteins
PubMed: 37060026
DOI: 10.1186/s12906-023-03946-5 -
Journal of Clinical Medicine Jun 2017Rheumatoid arthritis (RA) is a systemic autoimmune disease, caused by both genetic and environmental factors. Recently, investigators have focused on the gut microbiota,... (Review)
Review
Rheumatoid arthritis (RA) is a systemic autoimmune disease, caused by both genetic and environmental factors. Recently, investigators have focused on the gut microbiota, which is thought to be an environmental agent affecting the development of RA. Here we review the evidence from animal and human studies that supports the role of the gut microbiota in RA. We and others have demonstrated that the abundance of is increased in some early RA. We have also used gnotobiotic experiments to show that dysbiosis in RA patients contributed to the development of Th17 cell-dependent arthritis in intestinal microbiota-humanized SKG mice. On the other hand, from human gut microbiota suppressed the development of arthritis. In summary, species are involved in the pathogenesis of arthritis.
PubMed: 28598360
DOI: 10.3390/jcm6060060 -
Frontiers in Nutrition 2021Estrogen deficiency-induced depression is closely associated with an imbalance in intestinal microbiota and inflammation. (), an emerging probiotic, apparently improves...
BACKGROUND
Estrogen deficiency-induced depression is closely associated with an imbalance in intestinal microbiota and inflammation. (), an emerging probiotic, apparently improves inflammatory responses. This study aims to verify the antidepressant-like effects of and clarify its potential mechanisms.
METHODS
Mice were treated with and cohousing after ovariectomy (OVX). The changes in depression-like behaviors among mice were examined by behavioral tasks, and alterations in the microbiota were detected through 16S rRNA sequencing. Changes in neuronal injury, protein synthesis, inflammatory factors, intestinal permeability, and nerve proliferation were observed by H&E, Nissl staining, qRT-PCR, western blotting, and immunofluorescence.
RESULTS
significantly reduces depression-like behaviors and neuronal damage induced by estrogen deficiency. Additionally, significantly increases the abundance of intestinal flora, especially and . Meanwhile, the cohoused mice also had a better emotional state and neutral structure compared with OVX mice. was also found to upregulate tight junction proteins ZO-1, occludin, claudin-1, and MUC2 in the ileum and colon and reduce the levels of inflammatory factors VCAM, MCP-1, IL-6, IL-8, and TNF-α, mainly in the ileum, colon, and decrease the expression of COX-2, TLR4, Myd88, JNK, MCP-1, IL-6, IL-8, and TNF-α in the hippocampus. Moreover, significant downregulation of apoptosis (caspase-3 and caspase-8) and upregulation of neurotrophic factors (BDNF and Ki-67) were observed after treatment.
CONCLUSION
Our data show that significantly mitigates depression of OVX mice through improvement in intestinal microbiota to repair intestinal leakage and inhibit central inflammation to promote the expression of BDNF for hippocampal neurogenesis. may be therapeutically beneficial for PMD.
PubMed: 35155523
DOI: 10.3389/fnut.2021.805465 -
Frontiers in Medicine 2023EDP1815 is a non-colonizing pharmaceutical preparation of a single stain of isolated from the duodenum of a human donor. We report here preclinical and clinical studies...
INTRODUCTION
EDP1815 is a non-colonizing pharmaceutical preparation of a single stain of isolated from the duodenum of a human donor. We report here preclinical and clinical studies showing that the action of EDP1815, an orally delivered and gut restricted single strain of commensal bacteria can regulate inflammatory responses throughout the body.
METHODS
Supported by evidence for anti-inflammatory activity in three preclinical mouse models of Th1-, TH2-, and Th17-mediated inflammation, EDP1815 was tested clinically in three Phase 1b studies in patients with psoriasis, patients with atopic dermatitis, and healthy volunteers in a KLH skin challenge model.
RESULTS
Preclinically, EDP1815 was efficacious in all three mouse models of inflammation, showing reduction in skin inflammation as well as related tissue cytokines. In the Phase 1b studies, EDP1815 was found to be well tolerated by participants, with a safety profile comparable to placebo, including no severe or consistent side-effects reported, and no evidence of immunosuppression with no opportunistic infection occurring in these studies. In psoriasis patients, signs of clinical efficacy were seen after 4 weeks of treatment, which continued beyond the treatment period in the higher-dose cohort. In atopic dermatitis patients, improvements were seen throughout the key physician-and patient-reported outcomes. In a healthy-volunteer study of a KLH-induced skin inflammatory response, consistent anti-inflammatory effects were seen in two cohorts through imaging-based measures of skin inflammation.
DISCUSSION
This is the first report demonstrating clinical effects from targeting peripheral inflammation with a non-colonizing gut-restricted single strain of commensal bacteria, providing proof of concept for a new class of medicines. These clinical effects occur without systemic exposure of EDP1815 or modification of the resident gut microbiota, and with placebo-like safety and tolerability. The breadth of these clinical effects of EDP1815, combined with its excellent safety and tolerability profile and oral administration, suggests the potential for a new type of effective, safe, oral, and accessible anti-inflammatory medicine to treat the wide range of diseases driven by inflammation.: EudraCT # 2018-002807-32; EudraCT # 2018-002807-32; NL8676; https://clinicaltrials.gov/ct2/show/NCT03733353; http://www.trialregister.nl.
PubMed: 37215725
DOI: 10.3389/fmed.2023.1070433 -
The American Journal of Clinical... Oct 2021The gut microbiota (GM)-bone axis has emerged as a crucial mediator of bone homeostasis. Estrogen deficiency-induced bone loss is closely associated with an altered GM....
BACKGROUND
The gut microbiota (GM)-bone axis has emerged as a crucial mediator of bone homeostasis. Estrogen deficiency-induced bone loss is closely associated with an altered GM. However, the underlying mechanisms remain unclear.
OBJECTIVES
We sought to explore the putative effects of GM on estrogen deficiency-induced bone loss and determine a potential mechanism.
METHODS
Fecal samples collected from postmenopausal women with osteoporosis (PMO) and with normal bone mass (PMN) were examined by 16S ribosomal RNA (rRNA) gene sequencing and analysis. Prevotella histicola, a typical species of Prevotella, was orally given to female C57BL6/J mice after ovariectomy [ovariectomized (OVX)]. The primary outcomes were changes in bone microstructures as measured by micro-computed tomography scanning and bone histomorphometry analysis. Secondary outcomes included changes in osteoclast activity, the expression of osteoclastogenic cytokines, and gut permeability, which were measured by ELISA, qRT-PCR, western blot, and immunofluorescence.
RESULTS
As demonstrated through 16S rRNA gene sequencing and analysis, the GM in the PMO group featured a significantly decreased proportion of the genus Prevotella in comparison with that in the PMN group (∼60%, P < 0.05). In animal experiments, P. histicola-treated OVX mice maintained a relatively higher bone volume than OVX controls. Mechanistically, the protective effects of P. histicola on bone mass were found to be associated with its modulation of gut permeability as well as its inhibitory effects on osteoclast activity which function by attenuating osteoclastogenic cytokine expression.
CONCLUSIONS
The GM diversity and composition between the PMN and PMO groups were significantly different. In particular, the proportion of the genus Prevotella was notably higher in the PMN group, demonstrating its potential bone-protective effects on osteoporosis. Further animal study using osteoporotic mice showed P. histicola could prevent estrogen deficiency-induced bone loss through the GM-bone axis. Thus, P. histicola may serve as a therapeutic agent or target for osteoporosis treatment.
Topics: Animals; Cytokines; Estrogens; Female; Gastrointestinal Microbiome; Gene Expression Regulation; Humans; Mice; Mice, Inbred C57BL; Middle Aged; Osteoporosis; Osteoprotegerin; Ovariectomy; Postmenopause; Prevotella; RANK Ligand; RNA, Ribosomal, 16S; Random Allocation; Receptor Activator of Nuclear Factor-kappa B
PubMed: 34113963
DOI: 10.1093/ajcn/nqab194 -
Frontiers in Immunology 2020Gut microbiota has emerged as an important environmental factor in the pathobiology of multiple sclerosis (MS), an inflammatory demyelinating disease of the central... (Comparative Study)
Comparative Study
Gut microbiota has emerged as an important environmental factor in the pathobiology of multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system (CNS). Both genetic and environmental factors have been shown to play an important role in MS. Among genetic factors, the human leukocyte antigen (HLA) class II allele such as HLA-DR2, DR3, DR4, DQ6, and DQ8 show the association with the MS. We have previously used transgenic mice expressing MS susceptible HLA class II allele such as HLA-DR2, DR3, DQ6, and DQ8 to validate significance of HLA alleles in MS. Although environmental factors contribute to 2/3 of MS risk, less is known about them. Gut microbiota is emerging as an imporatnt environmental factor in MS pathogenesis. We and others have shown that MS patients have distinct gut microbiota compared to healthy control (HC) with a lower abundance of . Additionally, the abundance of increased in patients receiving disease-modifying therapies (DMTs) such as Copaxone and/or Interferon-beta (IFNβ). We have previously identified a specific strain of (), which can suppress experimental autoimmune encephalomyelitis (EAE) disease in HLA-DR3.DQ8 transgenic mice. Since Interferon-β-1b [IFNβ (Betaseron)] is a major DMTs used in MS patients, we hypothesized that treatment with the combination of and IFNβ would have an additive effect on the disease suppression. We observed that treatment with suppressed disease as effectively as IFNβ. Surprisingly, the combination of and IFNβ was not more effective than either treatment alone. alone or in combination with IFNβ increased the frequency and number of CD4FoxP3 regulatory T cells in the gut-associated lymphoid tissue (GALT). Treatment with alone, IFNβ alone, and in the combination decreased frequency of pro-inflammatory IFN-γ and IL17-producing CD4 T cells in the CNS. Additionally, alone or IFNβ alone or the combination treatments decreased CNS pathology, characterized by reduced microglia and astrocytic activation. In conclusion, our study indicates that the human gut commensal can suppress disease as effectively as commonly used MS drug IFNβ and may provide an alternative treatment option for MS patients.
Topics: Animals; Anti-Inflammatory Agents; Astrocytes; Central Nervous System; Encephalomyelitis, Autoimmune, Experimental; Female; Forkhead Transcription Factors; Gastrointestinal Microbiome; HLA-DQ beta-Chains; HLA-DRB1 Chains; Humans; Interferon-beta; Interferon-gamma; Interleukin-17; Intestines; Lymphoid Tissue; Male; Mice, Transgenic; Microglia; Prevotella; T-Lymphocytes, Regulatory
PubMed: 33362764
DOI: 10.3389/fimmu.2020.578648 -
The Preventive Effects of Probiotic on the Bone Loss of Mice with Ovariectomy-Mediated Osteoporosis.Microorganisms Apr 2023It has been demonstrated that the disturbance of gut microbiota (GM) is closely related to the reduction of bone mass and incidence of osteoporosis (OP). The aim of this...
It has been demonstrated that the disturbance of gut microbiota (GM) is closely related to the reduction of bone mass and incidence of osteoporosis (OP). The aim of this study is to investigate whether the supplementation of (Ph) can prevent the bone loss in mice with ovariectomy (OVX)-mediated OP, and further explore relevant mechanisms. Regular (once a day for 8 consecutive weeks) and quantitative (200 µL/d) perfusion of Ph (the bacteria that orally gavaged) was conducted starting from 1 week after the construction of mice models. Bone mass and bone microstructure were detected by Micro-computed tomography (Micro-CT). Expressions of intestinal permeability, pro-inflammatory cytokines, and osteogenic and osteoclastic activities of mice were analyzed by histological staining and immunohistochemistry (IHC). 16S rRNA high throughput sequencing technique was applied to analyze the alterations of composition, abundance, and diversity of collected feces. Regular and quantitative perfusion of Ph mitigated the bone loss in mice with OVX-mediated OP. Compared with OVX + PBS group, perfusion of Ph repressed osteoclastogenesis and promoted osteogenesis, reduced release of pro-inflammatory cytokine cytokines (interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α)), and reversed expressions of tight junction proteins (zonula occludens protein 1 (ZO-1) and Occludin). Besides, the perfusion of Ph improved the composition, abundance, and diversity of GM. Collectively, this study revealed that regular and quantitative perfusion of Ph can improve the bone loss in mice with OVX-mediated OP by repairing intestinal mucosal barrier damage, optimizing intestinal permeability, inhibiting release of pro-osteoclastogenic cytokines, and improving disturbance of GM.
PubMed: 37110373
DOI: 10.3390/microorganisms11040950