Gut microbiota–driven brain Aβ amyloidosis in mice requires microglia

2021 ◽  
Vol 219 (1) ◽  
Author(s):  
Hemraj B. Dodiya ◽  
Holly L. Lutz ◽  
Ian Q. Weigle ◽  
Priyam Patel ◽  
Julia Michalkiewicz ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Fecal Microbiota Transplantation ◽  
Critical Role ◽  
Amyloid Β ◽  
Fecal Microbiota ◽  
Degenerative Changes ◽  
High Dose ◽  
Male Mice ◽  
Treated Male ◽  
Plaque Pathology

We previously demonstrated that lifelong antibiotic (ABX) perturbations of the gut microbiome in male APPPS1-21 mice lead to reductions in amyloid β (Aβ) plaque pathology and altered phenotypes of plaque-associated microglia. Here, we show that a short, 7-d treatment of preweaned male mice with high-dose ABX is associated with reductions of Aβ amyloidosis, plaque-localized microglia morphologies, and Aβ-associated degenerative changes at 9 wk of age in male mice only. More importantly, fecal microbiota transplantation (FMT) from transgenic (Tg) or WT male donors into ABX-treated male mice completely restored Aβ amyloidosis, plaque-localized microglia morphologies, and Aβ-associated degenerative changes. Transcriptomic studies revealed significant differences between vehicle versus ABX-treated male mice and FMT from Tg mice into ABX-treated mice largely restored the transcriptome profiles to that of the Tg donor animals. Finally, colony-stimulating factor 1 receptor (CSF1R) inhibitor-mediated depletion of microglia in ABX-treated male mice failed to reduce cerebral Aβ amyloidosis. Thus, microglia play a critical role in driving gut microbiome–mediated alterations of cerebral Aβ deposition.

scholarly journals Sex-specific effects of microbiome perturbations on cerebral Aβ amyloidosis and microglia phenotypes

2019 ◽  
Vol 216 (7) ◽  
pp. 1542-1560 ◽  
Author(s):  
Hemraj B. Dodiya ◽  
Thomas Kuntz ◽  
Shabana M. Shaik ◽  
Caroline Baufeld ◽  
Jeffrey Leibowitz ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Amyloid Β ◽  
Fecal Microbiota ◽  
Male Mice ◽  
Female Mice ◽  
Antibiotic Cocktail ◽  
Specific Effects ◽  
Plaque Pathology ◽  
Microglial Morphology

We demonstrated that an antibiotic cocktail (ABX)-perturbed gut microbiome is associated with reduced amyloid-β (Aβ) plaque pathology and astrogliosis in the male amyloid precursor protein (APP)SWE/presenilin 1 (PS1)ΔE9 transgenic model of Aβ amyloidosis. We now show that in an independent, aggressive APPSWE/PS1L166P (APPPS1-21) mouse model of Aβ amyloidosis, an ABX-perturbed gut microbiome is associated with a reduction in Aβ pathology and alterations in microglial morphology, thus establishing the generality of the phenomenon. Most importantly, these latter alterations occur only in brains of male mice, not in the brains of female mice. Furthermore, ABX treatment lead to alterations in levels of selected microglial expressed transcripts indicative of the “M0” homeostatic state in male but not in female mice. Finally, we found that transplants of fecal microbiota from age-matched APPPS1-21 male mice into ABX-treated APPPS1-21 male restores the gut microbiome and partially restores Aβ pathology and microglial morphology, thus demonstrating a causal role of the microbiome in the modulation of Aβ amyloidosis and microglial physiology in mouse models of Aβ amyloidosis.

scholarly journals Rapid improvement in Alzheimer’s disease symptoms following fecal microbiota transplantation: a case report

2020 ◽  
Vol 48 (6) ◽  
pp. 030006052092593
Author(s):  
Sabine Hazan
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gut Microbiome ◽  
Fecal Microbiota Transplantation ◽  
Memory Loss ◽  
Amyloid Β ◽  
Fecal Microbiota ◽  
Symptom Improvement ◽  
Amyloid Β Peptide ◽  
Rapid Improvement

Alzheimer’s disease (AD), the most common form of dementia, is a leading cause of death and a major cause of morbidity in older people. The disease is characterized by progressive memory loss, cognitive impairment, and the cerebral accumulation of amyloid-β peptide. Given the health and economic impacts of AD, treatments that target the underlying etiology of AD or modify the course of the disease are of significant interest. The gut microbiome has been increasingly implicated in the pathogenesis of several neurological diseases, including multiple sclerosis and Parkinson’s disease. Furthermore, emerging evidence has demonstrated that there are alterations in gut microbiome composition in patients with AD, suggesting involvement of the microbiome–gut–brain axis. We present symptom improvement in a patient with AD following fecal microbiota transplantation for a Clostridioides difficile infection.

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

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 997 ◽  
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.

scholarly journals Fecal microbiota transplantation improves metabolism and gut microbiome composition in db/db mice

2020 ◽  
Vol 41 (5) ◽  
pp. 678-685 ◽  
Author(s):  
Pei-pei Zhang ◽  
Lin-lin Li ◽  
Xue Han ◽  
Qin-wei Li ◽  
Xu-hua Zhang ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Microbiome Composition

scholarly journals Effect of Fiber and Fecal Microbiota Transplantation Donor on Recipient Mice Gut Microbiota

2021 ◽  
Vol 12 ◽  
Author(s):  
Yifan Zhong ◽  
Jiahong Cao ◽  
Zhaoxi Deng ◽  
Yanfei Ma ◽  
Jianxin Liu ◽  
...  
Keyword(s):  
Random Forest ◽  
Gut Microbiota ◽  
Dietary Fiber ◽  
Fecal Microbiota Transplantation ◽  
Critical Role ◽  
Fecal Microbiota ◽  
Linear Discriminant ◽  
High Fiber ◽  
Significant Difference ◽  
Random Forest Models

Both fecal microbiota transplantation (FMT) and dietary fiber intervention were verified as effective ways to manipulate the gut microbiota, whereas little is known about the influence of the combined methods on gut microbiota. Here, we constructed “non-industrialized” and “industrialized” gut microbiota models to investigate the donor effect of FMT and diet effect in shaping the gut microbiota. Mice were transplanted fecal microbiota from domestic pig and received a diet with low-fiber (D) or high-fiber (DF), whereas the other two groups were transplanted fecal microbiota from wild pig and then received a diet with low-fiber (W) or high-fiber (WF), respectively. Gut microbiota of WF mice showed a lower Shannon and Simpson index (P < 0.05), whereas gut microbiota of W mice showed no significant difference than that of D and DF mice. Random forest models revealed the major differential bacteria genera between four groups, including Anaeroplasma or unclassified_o_Desulfovibrionales, which were influenced by FMT or diet intervention, respectively. Besides, we found a lower out-of-bag rate in the random forest model constructed for dietary fiber (0.086) than that for FMT (0.114). Linear discriminant analysis effective size demonstrated that FMT combined with dietary fiber altered specific gut microbiota, including Alistipes, Clostridium XIVa, Clostridium XI, and Akkermansia, in D, DF, W, and WF mice, respectively. Our results revealed that FMT from different donors coupled with dietary fiber intervention could lead to different patterns of gut microbiota composition, and dietary fiber might play a more critical role in shaping gut microbiota than FMT donor. Strategies based on dietary fiber can influence the effectiveness of FMT in the recipient.

scholarly journals Recent advances in modulating the microbiome

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 46 ◽  
Author(s):  
Eamonn M.M Quigley ◽  
Prianka Gajula
Keyword(s):  
Gut Microbiome ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Human Phenotype ◽  
Host Interactions ◽  
Healthy Humans ◽  
Probiotic Strains ◽  
The Many ◽  
Definition Of

We are in the midst of “the microbiome revolution”—not a day goes by without some new revelation on the potential role of the gut microbiome in some disease or disorder. From an ever-increasing recognition of the many roles of the gut microbiome in health and disease comes the expectation that its modulation could treat or prevent these very same diseases. A variety of interventions could, at least in theory, be employed to alter the composition or functional capacity of the microbiome, ranging from diet to fecal microbiota transplantation (FMT). For some, such as antibiotics, prebiotics, and probiotics, an extensive, albeit far from consistent, literature already exists; for others, such as other dietary supplements and FMT, high-quality clinical studies are still relatively few in number. Not surprisingly, researchers have turned to the microbiome itself as a source for new entities that could be used therapeutically to manipulate the microbiome; for example, some probiotic strains currently in use were sourced from the gastrointestinal tract of healthy humans. From all of the extant studies of interventions targeted at the gut microbiome, a number of important themes have emerged. First, with relatively few exceptions, we are still a long way from a precise definition of the role of the gut microbiome in many of the diseases where a disturbed microbiome has been described—association does not prove causation. Second, while animal models can provide fascinating insights into microbiota–host interactions, they rarely recapitulate the complete human phenotype. Third, studies of several interventions have been difficult to interpret because of variations in study population, test product, and outcome measures, not to mention limitations in study design. The goal of microbiome modulation is a laudable one, but we need to define our targets, refine our interventions, and agree on outcomes.

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 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.

scholarly journals The Role of Gut Microbiota in Lung Cancer: From Carcinogenesis to Immunotherapy

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiangjun Liu ◽  
Ye Cheng ◽  
Dan Zang ◽  
Min Zhang ◽  
Xiuhua Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Fecal Microbiota Transplantation ◽  
Checkpoint Inhibitors ◽  
Fecal Microbiota ◽  
Immune Homeostasis ◽  
Gut Dysbiosis ◽  
Underlying Mechanisms ◽  
And Function

The influence of microbiota on host health and disease has attracted adequate attention, and gut microbiota components and microbiota-derived metabolites affect host immune homeostasis locally and systematically. Some studies have found that gut dysbiosis, disturbance of the structure and function of the gut microbiome, disrupts pulmonary immune homeostasis, thus leading to increased disease susceptibility; the gut-lung axis is the primary cross-talk for this communication. Gut dysbiosis is involved in carcinogenesis and the progression of lung cancer through genotoxicity, systemic inflammation, and defective immunosurveillance. In addition, the gut microbiome harbors the potential to be a novel biomarker for predicting sensitivity and adverse reactions to immunotherapy in patients with lung cancer. Probiotics and fecal microbiota transplantation (FMT) can enhance the efficacy and depress the toxicity of immune checkpoint inhibitors by regulating the gut microbiota. Although current studies have found that gut microbiota closely participates in the development and immunotherapy of lung cancer, the mechanisms require further investigation. Therefore, this review aims to discuss the underlying mechanisms of gut microbiota influencing carcinogenesis and immunotherapy in lung cancer and to provide new strategies for governing gut microbiota to enhance the prevention and treatment of lung cancer.

Sign in / Sign up

Export Citation Format

Share Document