The Brain and the Microbiome
Summary:
There is a well-established, bi-directional gut-brain axis. The gut microbiome has been shown to have a major impact on brain function and diseases of the brain & nervous system. FMTs (Fecal Microbiota Transplants) are being shown to be a likely treatment and prevention for disorders of the brain.
General:
"It is now clear that the gut microbiota contributes significantly to the traits of humans as much as our genes, especially in the case of atherosclerosis, hypertension, obesity, diabetes, metabolic syndrome, inflammatory bowel disease (IBD), gastrointestinal tract malignancies, hepatic encephalopathy, allergies, behavior, intelligence, autism, neurological diseases, and psychological diseases. It has also been found that alteration of the composition of the gut microbiota in its host affects the behavior, intelligence, mood, autism, psychology, and migraines of its host through the gut-brain axis." (2018): https://www.frontiersin.org/articles/10.3389/fmicb.2018.01510/full
Reviews:
Review, 2023: Trust the gut: outcomes of gut microbiota transplant in metabolic and cognitive disorders https://www.sciencedirect.com/science/article/abs/pii/S0149763423001124 "comprehensive overview of studies in which FMT was used to cure or cause obesity, metabolic syndrome, T2DM, cognitive decline and Alzheimer’s disease"
Review, 2021: Gut microbiota alteration and modulation in psychiatric disorders: Current evidence on fecal microbiota transplantation https://www.sciencedirect.com/science/article/abs/pii/S0278584621000178
Review, 2021: Fecal Microbiota Transplantation: A New Therapeutic Attempt from the Gut to the Brain https://www.hindawi.com/journals/grp/2021/6699268/
Systematic Review, 2020: Effect of fecal microbiota transplant on symptoms of psychiatric disorders: a systematic review https://bmcpsychiatry.biomedcentral.com/articles/10.1186/s12888-020-02654-5 "There appears to be strong evidence for the treatment and transmission of psychiatric illnesses through FMT"
Review, 2018: Microbiome—The Missing Link in the Gut-Brain Axis: Focus on Its Role in Gastrointestinal and Mental Health https://www.mdpi.com/2077-0383/7/12/521/htm "mounting data that gut microbiota is the source of a number of neuroactive and immunocompetent substances, which shape the structure and function of brain regions involved in the control of emotions, cognition, and physical activity"
Review, 2018: Microorganisms’ Footprint in Neurodegenerative Diseases https://doi.org/10.3389/fncel.2018.00466 "The negative direct or indirect contributions of various microorganisms in onset or severity of some neurodegeneration disorders and interaction between human immune system and pathogenic microorganisms has been portrayed in this review article"
Review, 2018: The Brain-Gut-Microbiome Axis https://www.cmghjournal.org/article/S2352-345X(18)30060-2/fulltext
Review, 2017: Neuromicrobiology: how microbes influence the brain: https://pubs.acs.org/doi/pdfplus/10.1021/acschemneuro.7b00373 | via sci-hub: https://pubs.acs.org.sci-hub.se/doi/pdfplus/10.1021/acschemneuro.7b00373
Review, 2017: Gut reactions: How the blood–brain barrier connects the microbiome and the brain: https://journals.sagepub.com/doi/10.1177/1535370217743766
Review, 2017: Feeding the Microbiota-Gut-Brain Axis: Diet, Microbiome and Neuropsychiatry: https://www.sciencedirect.com/science/article/pii/S193152441630264X
Review, 2016: Cognitive Function and the Microbiome, International Review of Neurobiology: https://www.sciencedirect.com/science/article/pii/S0074774216301349
Review, 2015: Serotonin, tryptophan metabolism and the brain-gut-microbiome axis: https://www.sciencedirect.com/science/article/pii/S0166432814004768
Review, 2015: The impact of gut microbiota on brain and behaviour: implications for psychiatry: https://doi.org/10.1097/MCO.0000000000000221 - "The current narrative suggests that certain neuropsychiatric disorders might be treated by targeting the microbiota either by microbiota transplantation, antibiotics or psychobiotics."
Review, 2014: The effects of inflammation, infection and antibiotics on the microbiota-gut-brain axis: https://link.springer.com/chapter/10.1007%2F978-1-4939-0897-4_13
Review, 2013: Microbial Endocrinology in the Microbiome-Gut-Brain Axis: How Bacterial Production and Utilization of Neurochemicals Influence Behavior: https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1003726
Review, 2013: The role of gut microbiota in the gut-brain axis: current challenges and perspectives: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4875553/
Review, 2012: The impact of the gut microbiota on brain and behaviour: https://www.nature.com/articles/nrn3346
Review, 2012: Regulation of the stress response by the gut microbiota: implications for psychoneuroendocrinology: https://www.sciencedirect.com/science/article/abs/pii/S0306453012000935
Review, 2011: The microbiome-gut-brain axis: from bowel to behavior: https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2982.2010.01664.x/full
FMT:
The adoptive transfer of behavioral phenotype via the intestinal microbiota: experimental evidence and clinical implications (2013): https://doi.org/10.1016/j.mib.2013.06.004 "raising the possibility of using FMT for disorders of the central nervous system, and prompting caution in the selection of FMT donors"
Fecal Microbiota Transplantation Is a Promising Method to Restore Gut Microbiota Dysbiosis and Relieve Neurological Deficits after Traumatic Brain Injury (Feb 2021, rats) https://www.hindawi.com/journals/omcl/2021/5816837/ "FMT can [..] relieve neurological deficits possibly through the TMA-TMAO-MsrA signaling pathway after TBI"
Fecal Microbiota Transfer Attenuates Gut Dysbiosis and Functional Deficits After Traumatic Brain Injury (Jun 2022, mice) https://journals.lww.com/shockjournal/Abstract/2022/06000/Fecal_Microbiota_Transfer_Attenuates_Gut_Dysbiosis.10.aspx
Fecal microbiota transplantation can improve cognition in patients with cognitive decline and Clostridioides difficile infection (Aug 2022, n=10) https://www.aging-us.com/article/204230/text
Fecal microbiota transplantation ameliorates high-fat diet-induced memory impairment in mice (Jun 2024) https://onlinelibrary.wiley.com/doi/10.1111/jnc.16156
Fecal microbiota transplantation derived from mild cognitive impairment individuals impairs cerebral glucose uptake and cognitive function in wild-type mice: Bacteroidetes and TXNIP-GLUT signaling pathway (Sep 2024) https://forum.humanmicrobiome.info/threads/fecal-microbiota-transplantation-derived-from-mild-cognitive-impairmen.588/
Misc:
Gut microbiome regulates brain development: https://humanmicrobiome.info/maternity#brain-function
More in probiotic-specific page: https://humanmicrobiome.info/probiotics
Gut bacteria produce and consume neurotransmitters [1][2][3], along with gasotransmitters [1] that affect our brain, mind and behavior. As do gut fungi [1].
Gut microbes regulate serotonin: https://www.sci-news.com/medicine/gut-microbiota-physiology-04500.html
Microbial genes, brain & behaviour – epigenetic regulation of the gut–brain axis: To date, there is rapidly increasing evidence for host-microbe interaction on virtually all levels of complexity, ranging from direct cell-to-cell communication to extensive systemic signalling, and involving various organs and organ systems, including the central nervous system. As such, the discovery that differential microbial composition is associated with alterations in behavior and cognition has significantly contributed to establish the microbiota-gut-brain axis as an extension of the well-accepted gut-brain axis concept. (2013) https://onlinelibrary.wiley.com/doi/full/10.1111/gbb.12109
Gut bacteria regulate nerve fibre insulation. Research suggests that gut bacteria may directly affect brain structure and function, offering new ways to treat multiple sclerosis and psychiatric conditions (2016): https://www.theguardian.com/science/neurophilosophy/2016/apr/05/gut-bacteria-brain-myelin
Gut bacteria essential for neurogenesis; Antibiotics that kill gut bacteria also stop growth of new brain cells: https://www.cell.com/cell-reports/fulltext/S2211-1247%2816%2930518-6 - https://www.sciencedaily.com/releases/2016/05/160519130105.htm
Neuron destruction processes in the brain could be triggered by proteins produced by gut microbiota: https://www.ctvnews.ca/health/gut-microbiota-may-have-role-in-neurodegenerative-diseases-study-1.3107349
The intestinal microbiota affect central levels of brain-derived neurotropic factor and behavior in mice: https://www.gastrojournal.org/article/S0016-5085(11)00607-X/fulltext
Can You Blame Bad Behavior on Your Gut? Science Says Yes (May 2024, n=101) Impact of the gut microbiome composition on social decision-making https://forum.humanmicrobiome.info/threads/can-you-blame-bad-behavior-on-your-gut-science-says-yes-may-2024-n-101.510/
Gut microbiome composition and diversity are related to human personality traits (Mar 2020) https://www.sciencedirect.com/science/article/pii/S2452231719300181 - https://www.ox.ac.uk/news/2020-01-23-gut-bacteria-linked-personality
Correlation between gut microbiota and personality in adults: A cross-sectional study (2017): https://www.sciencedirect.com/science/article/pii/S0889159117305536
Associations among diet, the gastrointestinal microbiota, and negative emotional states in adults (2019): https://www.tandfonline.com/doi/abs/10.1080/1028415X.2019.1582578 "results suggest GI microbes are related to mood in adults without diagnosed mood disorders and that these relationships differ by sex and are influenced by dietary fiber intake"
The Virus That Could Cure Alzheimer’s, Parkinson’s, and More: https://www.pbs.org/wgbh/nova/next/body/phage-alzheimers-cure/
Gut microbiome populations are associated with structure-specific changes in white matter architecture (2018): https://www.nature.com/articles/s41398-017-0022-5
"Although the results cannot prove causality, these findings provide evidence for the involvement of infections and the immune system in the etiology of a wide range of mental disorders in children and adolescents" https://theconversation.com/how-childhood-infections-and-antibiotics-may-increase-risks-of-mental-illness-110965 A Nationwide Study in Denmark of the Association Between Treated Infections and the Subsequent Risk of Treated Mental Disorders in Children and Adolescents (Dec 2018).
"In conclusion, we demonstrate a molecular basis for how the host microbiome is crucial for a normal behavioural response during social interaction. Our data further suggest that social behaviour is correlated with the gene-expression response in the amygdala, established during neurodevelopment as a result of host-microbe interactions." (2018) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5995540/
A new pathway for the gut microbiota to modulate the brain: activation of pattern-recognition receptors by microbial products (peptidoglycan-sensing molecule Pglyrp2) (2017): https://www.nature.com/articles/mp2016210
Microbiota and host determinants of behavioural phenotype in maternally separated mice: https://www.nature.com/ncomms/2015/150728/ncomms8735/full/ncomms8735.html - "MS-induced changes in host physiology lead to intestinal dysbiosis"
Zika, Herpes, and West Nile viruses damage adult brains: https://www.invisiverse.com/news/viruses-might-cause-brain-changes-learning-problems-0177641/ - https://www.washingtonpost.com/news/to-your-health/wp/2017/11/07/new-evidence-of-brain-damage-from-west-nile-virus-scientists-say/ - https://www.pbs.org/wgbh/nova/next/body/zika-might-cause-brain-damage-in-adults-too/ - https://www.cell.com/cell-stem-cell/pdf/S1934-5909(16)30252-1.pdf - https://www.sciencedaily.com/releases/2017/07/170710122959.htm
ADHD:
Review, Jan 2022: The Role of Gut Microbiota-Brain Axis in Pathophysiology of ADHD: A Systematic Review https://journals.sagepub.com/doi/10.1177/10870547211073474
Review, Jun 2020: "The purpose of this review is to evaluate the most recent literature on the role of the gut microbiome in ADHD" https://www.frontiersin.org/articles/10.3389/fpsyt.2020.00623/full Current Limitations for the Assessment of the Role of the Gut Microbiome for Attention Deficit Hyperactivity Disorder (ADHD).
A case report of improvement on ADHD symptoms after fecal microbiota transplantation with gut microbiome profiling pre- and post-procedure (Sep 2022) https://www.tandfonline.com/doi/abs/10.1080/03007995.2022.2129232
Gut microbiota signature in treatment-naïve attention-deficit/hyperactivity disorder (n=200, Jul 2021) https://www.nature.com/articles/s41398-021-01504-6
ADHD-originating in the gut? The emergence of a new explanatory model (2018): https://doi.org/10.1016/j.mehy.2018.08.022
Gut microbiota from persons with attention-deficit/hyperactivity disorder affects the brain in mice (Apr 2020) https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-020-00816-x
ALS:
Fecal microbiota transplantation significantly improved respiratory failure of amyotrophic lateral sclerosis (May 2024, n=2) https://www.tandfonline.com/doi/full/10.1080/19490976.2024.2353396
Washed microbiota transplantation stopped the deterioration of amyotrophic lateral sclerosis: the first case report and narrative review (Jun 2022) https://www.jbr-pub.org.cn/article/doi/10.7555/JBR.36.20220088
Potential roles of gut microbiome and metabolites in modulating ALS in mice (July 2019) https://www.nature.com/articles/s41586-019-1443-5 "In humans, we identify distinct microbiome and metabolite configurations"
Rebalancing gut microbiome lengthens survival in mouse model of ALS. Target Intestinal Microbiota to Alleviate Disease Progression in Amyotrophic Lateral Sclerosis (2017) https://www.sciencedaily.com/releases/2017/01/170129084234.htm
People with amyotrophic lateral sclerosis (ALS) have an altered composition of their gut microbial community, with an increase in harmful microbes and a decrease in beneficial microorganisms, according to a new small study https://alsnewstoday.com/2019/08/08/altered-gut-microbiota-als-patients-could-drive-digestive-problems. Intestinal microbiota composition in patients with amyotrophic lateral sclerosis (Aug 2019).
Alzheimer’s:
Review, Oct 2022: Intestinal Flora Affect Alzheimer's Disease by Regulating Endogenous Hormones https://link.springer.com/article/10.1007/s11064-022-03784-w
Perspective, Sep 2022: Scientists have proposed a new mechanistic model (AD2) for Alzheimer's, looking at it not as a brain disease, but as a chronic autoimmune condition that attacks the brain. https://www.sciencedaily.com/releases/2022/09/220927111332.htm Alzheimer's disease as an innate autoimmune disease (AD2): A new molecular paradigm.
Review, Sep 2021: Analysis the Link between Periodontal Diseases and Alzheimer’s Disease: A Systematic Review. https://www.mdpi.com/1660-4601/18/17/9312 "The current review suggests an association between periodontal disease and Alzheimer’s disease. The treatment of periodontal disease could be a way to explore Alzheimer’s disease prevention"
Review, Mar 2019: The Role of Gut Microbiota in Pathogenesis of Alzheimer's Disease https://onlinelibrary.wiley.com/doi/abs/10.1111/jam.14264
Review, 2018: The Gut Microbiome Alterations and Inflammation-Driven Pathogenesis of Alzheimer’s Disease—a Critical Review: https://link.springer.com/article/10.1007/s12035-018-1188-4
Review, 2018: Microbiome-Mediated Upregulation of MicroRNA-146a in Sporadic Alzheimer’s Disease https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5867462/
Review, 2016: Alzheimer’s disease and gut microbiota: https://link.springer.com/article/10.1007%2Fs11427-016-5083-9
Review, 2016: Role of gut microbiota and nutrients in amyloid formation and pathogenesis of Alzheimer disease: https://nutritionreviews.oxfordjournals.org/content/74/10/624
FMT:
Effect of altered gene expression in lipid metabolism on cognitive improvement in patients with Alzheimer’s dementia following fecal microbiota transplantation: a preliminary study (Jan 2024, n=5) https://journals.sagepub.com/doi/10.1177/17562864231218181 "Significant improvements in cognitive function were seen"
Fecal Microbiota Transplantation Reduces Pathology and Improves Cognition in a Mouse Model of Alzheimer’s Disease (Dec 2022) https://www.mdpi.com/2073-4409/12/1/119
Transfer of a healthy microbiota reduces amyloid and tau pathology in an Alzheimer’s disease animal model (Aug 2019) https://gut.bmj.com/content/early/2019/08/29/gutjnl-2018-317431 "results indicate that microbiota-mediated intestinal and systemic immune aberrations contribute to the pathogenesis of AD"
Cognitive function improvement after fecal microbiota transplantation in Alzheimer’s dementia patient: a case report (Jul 2021) https://www.tandfonline.com/doi/full/10.1080/03007995.2021.1957807
Rapid improvement in Alzheimer’s disease symptoms following fecal microbiota transplantation: a case report (Jun 2020) https://journals.sagepub.com/doi/10.1177/0300060520925930
Alzheimer’s symptoms can be transferred to a healthy young organism via the gut microbiota (Oct 2023, FMT from Alz patients to rats) https://academic.oup.com/brain/advance-article/doi/10.1093/brain/awad303/7308687 Microbiota from Alzheimer’s patients induce deficits in cognition and hippocampal neurogenesis [in rats].
Multi-strain probiotics ameliorate Alzheimer’s-like cognitive impairment and pathological changes through the AKT/GSK-3β pathway in senescence-accelerated mouse prone 8 mice (Mar 2024) https://www.sciencedirect.com/science/article/abs/pii/S088915912400312X
Corroboration of a Major Role for Herpes Simplex Virus Type 1 in Alzheimer’s Disease (2018): https://www.frontiersin.org/articles/10.3389/fnagi.2018.00324/full
Infectious Theory of Alzheimer's Disease Draws Fresh Interest (2018): https://www.npr.org/sections/health-shots/2018/09/09/645629133/infectious-theory-of-alzheimers-disease-draws-fresh-interest
Periodontal disease bacteria may kick-start Alzheimer's. Chronic oral application of a periodontal pathogen results in brain inflammation, neurodegeneration and amyloid beta production in wild type mice (2018): https://medicalxpress.com/news/2018-10-periodontal-disease-bacteria-kick-start-alzheimer.html
A Common Gum Infection Bacteria (P. gingivalis) May Also be Causing Alzheimer’s. Porphyromonas gingivalis in Alzheimer’s disease brains: Evidence for disease causation and treatment with small-molecule inhibitors (Jan 2019) https://blogs.discovermagazine.com/d-brief/2019/01/23/dental-infection-may-spur-alzheimers-disease
Association between Alzheimer’s Disease and Oral and Gut Microbiota: Are Pore Forming Proteins the Missing Link? (2018): https://content.iospress.com/articles/journal-of-alzheimers-disease/jad180319
Mapping The Brain's Microbiome: Can Studying Germs In The Brain Lead To A Cure For Alzheimer's? (2017) https://www.forbes.com/sites/robinseatonjefferson/2017/07/28/mapping-the-brains-microbiome-can-studying-germs-in-the-brain-lead-to-a-cure-for-alzheimers/ | Alt links: p1 https://archive.is/vTdFK p2 https://archive.is/8tG5p
Antibiotics weaken Alzheimer's disease progression through changes in the gut microbiome (2016): https://www.eurekalert.org/pub_releases/2016-07/uocm-awa071516.php
Researchers Identify Virus and Two Types of Bacteria as Major Causes of Alzheimer’s (2016). “We are saying there is incontrovertible evidence that Alzheimer’s Disease has a dormant microbial component, and that this can be woken up by iron dysregulation." https://neurosciencenews.com/microbes-alzheimers-neurology-3826/
The gut microbiota-derived metabolite trimethylamine N-oxide [that has been implicated in human disease pathogenesis] is elevated in Alzheimer’s disease (2018): https://doi.org/10.1186/s13195-018-0451-2
Reduction of Abeta amyloid pathology in APPPS1 transgenic mice in the absence of gut microbiota (2017): https://www.nature.com/articles/srep41802
Protective Roles of Intestinal Microbiota derived Short Chain Fatty Acids in Alzheimer's Disease-type Beta-Amyloid Neuropathological Mechanisms (2017): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5958896/
Gut microbiome alterations in Alzheimer’s disease (2017). https://www.nature.com/articles/s41598-017-13601-y
Autism:
Review, 2019: Crosstalk Between the Microbiome and Gestational Immunity in Autism-Related Disorders https://www.liebertpub.com/doi/full/10.1089/dna.2019.4653 "recent findings identify the immune system as a link between gut microbiota and the brain in neurodevelopmental disorders, and suggest that targeting the microbiome and maternal immune responses during gestation may offer strategies to limit autism development in at-risk pregnancies"
Review, 2018: The Perturbance of Microbiome and Gut-Brain Axis in Autism Spectrum Disorders https://www.mdpi.com/1422-0067/19/8/2251/htm
Review, 2018: Early Disruption of the Microbiome Leading to Decreased Antioxidant Capacity and Epigenetic Changes: Implications for the Rise in Autism https://doi.org/10.3389/fncel.2018.00256
Review, 2016: Gut Microbiota and Autism: Key Concepts and Findings: https://link.springer.com/article/10.1007%2Fs10803-016-2960-9
FMT:
Beneficial Effects of Repeated Washed Microbiota Transplantation in Children With Autism (Jun 2022) https://www.frontiersin.org/articles/10.3389/fped.2022.928785/full "significantly improved ASD and GI symptoms and sleep disorders in children with ASD, and reduced systemic inflammation"
Fecal Microbiota Transplantation Relieves Gastrointestinal and Autism Symptoms by Improving the Gut Microbiota in an Open-Label Study (Oct 2021, n=40) https://web.archive.org/web/20220709204449/https://old.reddit.com/r/HumanMicrobiome/comments/qo26v6/fecal_microbiota_transplantation_relieves/ One Donor. Two routes of administration. 1x/week, 4 weeks. Neither vancomycin nor proton pump inhibitors (PPIs) was given before FMT.
ASU 10 week FMT trial shows improvements (2017): https://autism.asu.edu/ - https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-016-0225-7 | 2 year follow up sees nearly 50% reduction in symptoms (April 2019): https://asunow.asu.edu/20190409-discoveries-autism-symptoms-reduced-nearly-50-percent-two-years-after-fecal-transplant
"Fecal microbiota transplant (FMT) via gavage from autistic children donors to mice, led to the colonization of ASD-like microbiota and autistic behaviors" (Jul 2022) https://medicalxpress.com/news/2022-07-evidence-hints-role-gut-microbiota.html Modifications of Behavior and Inflammation in Mice Following Transplant with Fecal Microbiota from Children with Autism.
Distinct Fecal and Plasma Metabolites in Children with Autism Spectrum Disorders and Their Modulation after Microbiota Transfer Therapy (Oct 2020) https://msphere.asm.org/content/5/5/e00314-20 "Our results provide evidence that changes in metabolites are one mechanism of the gut-brain connection mediated by the gut microbiota and offer plausible clinical evidence for a promising autism treatment and biomarkers"
A Novel and Reliable Rat Model of Autism (Mar 2021) https://www.frontiersin.org/articles/10.3389/fpsyt.2021.549810/full "We transplanted the fecal sample extract of ASD children into pregnant rats. The FMT autism rat model has high structural validity, and the FMT model is likely to be a new and reliable potential animal model of ASD"
Parents:
Autism Risk Determined by Health of Mom’s Gut, UVA Research Reveals. "as a result of microflora-associated calibration of gestational IL-17a (inflammatory molecule interleukin-17a) responses" (2018): https://archive.fo/qKW3a - Cutting Edge: Critical Roles for Microbiota-Mediated Regulation of the Immune System in a Prenatal Immune Activation Model of Autism (2018) https://www.jimmunol.org/content/early/2018/06/29/jimmunol.1701755
Research finds potential mechanism linking autism, intestinal inflammation https://medicalxpress.com/news/2021-12-potential-mechanism-linking-autism-intestinal.html Maternal gut bacteria drive intestinal inflammation in offspring with neurodevelopmental disorders by altering the chromatin landscape of CD4+ T cells (Dec 2021, mice)
Correlation of Gut Microbiome Between ASD Children and Mothers and Potential Biomarkers for Risk Assessment (Apr 2019) https://www.sciencedirect.com/science/article/pii/S1672022919300634 "The identified patterns of mother–child gut microbiome profiles may be important for assessing risks during the early stage and planning of personalized treatment and prevention of ASD via microbiota modulation"
Dysbiotic microbiota in autistic children and their mothers: persistence of fungal and bacterial wall-deficient L-form variants in blood (Sep 2019): https://www.nature.com/articles/s41598-019-49768-9 "autistic children may be born already colonized with fungi, while a “silent aspergillosis” could contribute or even be a leading cause for neurodevelopmental disorders in the early childhood"
Children With Autism Carry Unique Gut Flora. This may lead to a more objective diagnostic tool (Jul 2024, n=1627) https://forum.humanmicrobiome.info/threads/children-with-autism-carry-unique-gut-flora-this-may-lead-to-a-more-ob.477/ Multikingdom and functional gut microbiota markers for autism spectrum disorder.
Altered gut microbiota correlates with behavioral problems but not gastrointestinal symptoms in individuals with autism (Sep 2022, n=113) https://www.sciencedirect.com/science/article/pii/S0889159122003713
The microbiota modulates gut physiology and behavioral abnormalities associated with autism/neurodevelopmental disorders (2013): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3897394/
Alteration of gut microbiota-associated epitopes (MEs) in children with autism spectrum disorders (2018): https://doi.org/10.1016/j.bbi.2018.10.006 "thirty-four MEs identified were potential biomarker of ASD, and alterations in MEs may contribute to abnormalities in gut immunity and/or homeostasis in ASD children"
Autism, antibiotics & probiotics: https://jeffreydachmd.com/2015/05/curing-autism-with-antibiotics/ - https://www.healio.com/infectious-disease/pediatric-id/news/online/%7Bf49b2afe-1b1e-4f66-9a3f-ffc9f68b40bf%7D/baylor-investigates-antibiotic-use-childrens-improved-autism-symptoms
A single species of gut bacteria can reverse autism-related social behavior in mice. Microbial Reconstitution Reverses Maternal Diet-Induced Social and Synaptic Deficits in Offspring (2016): https://www.sciencedaily.com/releases/2016/06/160616140723.htm | Nearly identical 2018 follow up study: Mechanisms Underlying Microbial-Mediated Changes in Social Behavior in Mouse Models of Autism Spectrum Disorder https://dx.doi.org/10.1016/j.neuron.2018.11.018
Depression and anxiety:
Systematic Review, Jun 2020: Altered Composition of Gut Microbiota in Depression: A Systematic Review https://www.frontiersin.org/articles/10.3389/fpsyt.2020.00541/full
Review, 2019: Effects of regulating intestinal microbiota on anxiety symptoms: A systematic review https://gpsych.bmj.com/content/32/2/e100056 "more than half of the studies included showed it was positive to treat anxiety symptoms by regulation of intestinal microbiota. Non-probiotic interventions were more effective than the probiotic interventions"
Review, 2018: Gut microbiome and depression: what we know and what we need to know: https://www.degruyter.com/view/j/revneuro.ahead-of-print/revneuro-2017-0072/revneuro-2017-0072.xml
Review, 2018: The Role of Microbiome in Insomnia, Circadian Disturbance and Depression https://www.frontiersin.org/articles/10.3389/fpsyt.2018.00669/full
FMT:
"FMT not only improves the symptoms of constipation, but also relieves depression" https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-021-03152-2 Effect of fecal microbiota transplantation in patients with slow transit constipation and the relative mechanisms based on the protein digestion and absorption pathway (Dec 2021, n=8)
Fecal Microbiota Transplantation (FMT) as an Adjunctive Therapy for Depression—Case Report (Feb 2022, n=2 women, 50-60 yr old, 30 frozen capsules) https://www.frontiersin.org/articles/10.3389/fpsyt.2022.815422/full "Both improved their depressive symptoms 4 weeks after the transplantation"
The multiple effects of fecal microbiota transplantation on diarrhea-predominant irritable bowel syndrome (IBS-D) patients with anxiety and depression behaviors (Dec 2021, n=18) https://microbialcellfactories.biomedcentral.com/articles/10.1186/s12934-021-01720-1 "FMT can effectively alleviate the anxiety and depression behaviors of IBS-D patients and reduce the IBS-SSS score"
Faecal microbiota transplantation from patients with depression or healthy individuals into rats modulates mood-related behaviour (Nov 2021) https://www.nature.com/articles/s41598-021-01248-9 "there was no difference in behaviour between FMT-MDD FRL rats and negative controls, indicating that FMT-Healthy FRL rats received beneficial bacteria"
Fecal microbiota transplantation in an elderly patient with mental depression (Feb 2019) https://www.cambridge.org/core/journals/international-psychogeriatrics/article/fecal-microbiota-transplantation-in-an-elderly-patient-with-mental-depression/F60C1C353A935643E2328A4858928DEC
Therapeutic effect of fecal microbiota transplantation on chronic unpredictable mild stress-induced depression (Jul 2022) https://www.frontiersin.org/articles/10.3389/fcimb.2022.900652/full
The effect of fecal microbiota transplantation on psychiatric symptoms among patients with irritable bowel syndrome, functional diarrhea and functional constipation: An open-label observational study (2018): https://www.jad-journal.com/article/S0165-0327(18)30193-9/fulltext - FMT improves psych symptoms even when it doesn't change IBS symptoms.
FMT transfer of depression-like behavior; this study demonstrates that dysbiosis of the gut microbiome may have a causal role in the development of depressive-like behaviors (2016): https://www.nature.com/articles/mp201644
Gut bacteria-driven homovanillic acid alleviates depression by modulating synaptic integrity (Apr 2024, mice) https://www.sciencedirect.com/science/article/pii/S1550413124000895
The gut microbiome regulates the increases in depressive-type behaviors and in inflammatory processes in the ventral hippocampus of stress vulnerable rats (Mar 2019) https://www.eurekalert.org/pub_releases/2019-05/chop-tgb050619.php
The neuroactive potential of the human gut microbiota in quality of life and depression (2019): https://www.nature.com/articles/s41564-018-0337-x "Our results provide population-scale evidence for microbiome links to mental health, while emphasizing confounder importance"
Gut microbiota regulates mouse behaviors through glucocorticoid receptor pathway genes in the hippocampus (2018): https://www.nature.com/articles/s41398-018-0240-5
Microbiota Modulate Anxiety-Like Behavior and Endocrine Abnormalities in Hypothalamic-Pituitary-Adrenal Axis (2017): https://www.frontiersin.org/articles/10.3389/fcimb.2017.00489/full
Immobilization stress-induced Escherichia coli causes anxiety by inducing NF-κB activation through gut microbiota disturbance (2018): https://www.nature.com/articles/s41598-018-31764-0 "However, the amelioration of gastrointestinal inflammation by treatment with probiotics including L. johnsonii can alleviate anxiety"
The outer membrane protein Amuc_1100 of Akkermansia muciniphila alleviates the depression-like behavior of depressed mice induced by chronic stress (Jun 2021) https://www.sciencedirect.com/science/article/abs/pii/S0006291X21009347
Link between intestinal bacteria, depression found (2015): https://www.sciencedaily.com/releases/2015/07/150728110734.htm
Effects of intestinal microbiota on anxiety-like behavior (2011): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181531/
Dementia:
Review, 2018: Gut microbiota, cognitive frailty and dementia in older individuals: a systematic review https://www.dovepress.com/gut-microbiota-cognitive-frailty-and-dementia-in-older-individuals-a-s-peer-reviewed-fulltext-article-CIA "Gut microbiota modulation of cognitive function represents a promising area of research for identifying novel preventive and treatment strategies against dementia"
Analysis of the relationship between the gut microbiome and dementia: a cross-sectional study conducted in Japan (Jan 2019): https://www.nature.com/articles/s41598-018-38218-7 "We have shown that components of the gut microbiome, in particular Bacteroides and ‘other’ bacteria, are independently associated with dementia, and these associations are stronger than those of traditional dementia biomarkers"
Herpes virus infection may increase likelihood of dementia (2018): https://www.medicalnewsbulletin.com/herpes-virus-infection-increase-dementia - Herpes Viruses and Senile Dementia: First Population Evidence for a Causal Link (2018): https://doi.org/10.3233/JAD-180266
Gastrointestinal tract microbiota are directly linked to dementia pathogenesis through triggering metabolic diseases and low-grade inflammation progress (2016) https://link.springer.com/article/10.1007%2Fs13238-016-0338-6
Multiple sclerosis (MS):
Review, 2023: The role of Fecal Microbiota Transplantation (FMT) in treating patients with multiple sclerosis https://www.tandfonline.com/doi/full/10.1080/14737175.2023.2250919
Review, 2018: The Gut Microbiome and Multiple Sclerosis - "We propose considering the gut microbiome as the major environmental risk factor for CNS demyelinating disease" https://perspectivesinmedicine.cshlp.org/content/early/2018/01/08/cshperspect.a029017
Review, 2017: Gut microbiome in multiple sclerosis: The players involved and the roles they play https://doi.org/10.1080/19490976.2017.1349041
Gut Microbiota Composition Is Causally Linked to Multiple Sclerosis: A Mendelian Randomization Analysis (Jul 2024) https://www.mdpi.com/2076-2607/12/7/1476
Gut Bacteria Toxin Linked to Onset and Relapse of Multiple Sclerosis (2023) https://www.technologynetworks.com/immunology/news/gut-bacteria-toxin-linked-to-onset-and-relapse-of-multiple-sclerosis-371625 Epsilon toxin-producing Clostridium perfringens colonize the MS gut and epsilon toxin overcomes immune privilege.
Inflammatory molecules can trigger multiple sclerosis by regulating the gut microbiota (Feb 2021, mice) https://microbiomepost.com/inflammatory-molecules-can-trigger-multiple-sclerosis-by-regulating-the-gut-microbiota/ IL-17 controls central nervous system autoimmunity through the intestinal microbiome.
A new study reports T cells are activated in the intestines and migrate to the brain, causing an inflammatory cascade that may lead to multiple sclerosis. Researchers say the gut microbiome may play a more significant role in the development and progression of MS than previously believed. (Oct 2018) https://neurosciencenews.com/multiple-sclerosis-gut-flora-10003/
Researchers at the University of Toronto and UC San Francisco have discovered that the intestine is the source of immune cells that reduce brain inflammation in people with multiple sclerosis (MS) https://www.ucsf.edu/news/2018/12/412941/gut-immune-cells-cut-inflammation-multiple-sclerosis. Recirculating Intestinal IgA-Producing Cells Regulate Neuroinflammation via IL-10 (2019): https://doi.org/10.1016/j.cell.2018.11.035
Researchers Uncover Gut Bacteria's Potential Role In Multiple Sclerosis. "We essentially discovered a remote control by which the gut flora can control what is going on at a distant site in the body, in this case the central nervous system" (2018) https://archive.fo/UyVvi
Multiple Sclerosis-Associated Changes in the Composition and Immune Functions of Spore-Forming Bacteria (2018): https://doi.org/10.1128/mSystems.00083-18
The makeup of the microbial world in the gut is increasingly recognized as a potential link to the development of the debilitating neurological disease multiple sclerosis. (2016) https://www.labnews.co.uk/features/head-gut-12-12-2016/
Gut bacteria at a young age can contribute to multiple sclerosis disease onset and progression (2017): https://www.sciencedaily.com/releases/2017/11/171117115446.htm
Gut bacteria from multiple sclerosis patients modulate human T cells and exacerbate symptoms in mouse models (2017) https://www.pnas.org/content/early/2017/09/05/1711235114
The microbiota regulates murine inflammatory responses to toxin-induced CNS demyelination but has minimal impact on remyelination (2019) https://www.pnas.org/content/early/2019/11/15/1905787116
Gut microbiota from multiple sclerosis patients enables spontaneous autoimmune encephalomyelitis in mice (2017) https://www.pnas.org/content/early/2017/09/05/1711233114
Human gut microbe may lead to treatment for multiple sclerosis. Research team tested gut microbial samples from patients on a mouse model of MS. Of three bacterial strains, they discovered that one microbe, Prevotella histicola, effectively suppressed immune disease in the preclinical model of MS. (2017) https://www.eurekalert.org/pub_releases/2017-08/mc-hgm080417.php
High frequency of intestinal TH17 cells correlates with microbiota alterations and disease activity in multiple sclerosis. Our data demonstrate that brain autoimmunity is associated with specific microbiota modifications and excessive TH17 cell expansion in the human intestine. (2017) https://advances.sciencemag.org/content/3/7/e1700492
Hidden herpes virus may play key role in MS, other brain disorders. The ubiquitous human herpesvirus 6 may play a critical role in impeding the brain's ability to repair itself in diseases like multiple sclerosis. (2017) https://www.sciencedaily.com/releases/2017/07/170710122959.htm
Engineered probiotic developed to treat multiple sclerosis (Aug 2023, mice) https://medicalxpress.com/news/2023-08-probiotic-multiple-sclerosis.html Lactate limits CNS autoimmunity by stabilizing HIF-1α in dendritic cells.
FMT:
Fecal microbiota transplantation associated with 10 years of stability in a patient with SPMS (2018): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5882466/ -- A few other cases.
Probiotics:
Engineered probiotic developed to treat multiple sclerosis (Aug 2023, mice) https://news.harvard.edu/gazette/story/2023/08/engineered-probiotic-developed-to-treat-multiple-sclerosis/ Lactate limits CNS autoimmunity by stabilizing HIF-1α in dendritic cells.
Parkinsons:
Review, 2024: Exploring Fecal Microbiota Transplantation for Modulating Inflammation in Parkinson’s Disease: A Review of Inflammatory Markers and Potential Effects https://www.mdpi.com/1422-0067/25/14/7741 "FMT emerges as a potential therapeutic strategy for PD. It may mitigate inflammation by restoring gut homeostasis. Preclinical studies in animal models and initial clinical trials have shown promising results"
Review, 2019: The impact of indigenous microbes on Parkinson's disease https://doi.org/10.1016/j.nbd.2019.03.014 "the gastrointestinal microbiome influences every organ system in the body; there is growing appreciation for the roles of both gastrointestinal function and its resident microbes within this disease state"
Review, 2019: Microbiome, Parkinson’s Disease and Molecular Mimicry https://www.mdpi.com/2073-4409/8/3/222/htm "This has supported the hypothesis that the resident microbial community, commonly referred to as microbiota, might play a causative role in the development of PD"
Review, 2018: Stomaching the Possibility of a Pathogenic Role for Helicobacter pylori in Parkinson’s Disease https://dx.doi.org/10.3233/JPD-181327
Review, 2018: Can the gut be the missing piece in uncovering PD pathogenesis? https://doi.org/10.1016/j.parkreldis.2018.11.014
Review, 2017: Microbes Tickling Your Tummy: the Importance of the Gut-Brain Axis in Parkinson’s Disease https://link.springer.com/article/10.1007%2Fs40473-017-0129-2
FMT:
Fecal microbiota transplant eases Parkinson’s symptoms (Mar 2024, n=46) https://forum.humanmicrobiome.info/threads/fecal-microbiota-transplant-eases-parkinsons-symptoms-apr-2024-n-46-sa.335/ Safety and efficacy of faecal microbiota transplantation in patients with mild to moderate Parkinson's disease (GUT-PARFECT): a double-blind, placebo-controlled, randomised, phase 2 trial
Efficacy of fecal microbiota transplantation in patients with Parkinson’s disease: clinical trial results from a randomized, placebo-controlled design (Dec 2023, n=56) https://www.tandfonline.com/doi/full/10.1080/19490976.2023.2284247 "no severe adverse effects, and patients receiving FMT showed significant improvement compared to the placebo group"
Fecal microbiota transplant as a potential treatment for Parkinson's disease – A case series (Jun 2021, n=6) https://www.sciencedirect.com/science/article/abs/pii/S0303846721003206 "FMT resulted in improvement in Parkinson's Disease motor symptoms and non-motor symptoms at 6 months. One patient had a serious adverse event requiring admission for observation only, and no adverse events were observed in all other patients."
Evaluation of fecal microbiota transplantation in Parkinson's disease patients with constipation (May 2021, n=11) https://archive.ph/6dFsJ "FMT might be a therapeutic potential for reconstructing the gut microbiota of PD patients and improving their motor and non-motor symptoms"
Fecal microbiota transplantation therapy for Parkinson's disease. A preliminary study (Aug 2020, n=15) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7458210/ "We conclude that FMT can relieve the motor and non-motor symptoms with acceptable safety in PD. Compared with nasointestinal FMT, colonic FMT seems better and preferable."
Chinese case report of patient with Parkinsons and constipation, both of which improved after FMT: https://journals.lww.com/md-journal/fulltext/2019/06280/Fecal_microbiota_transplantation_to_treat.56.aspx Fecal microbiota transplantation to treat Parkinson's disease with constipation (Jun 2019).
Transplantation of fecal microbiota, from normal mice on Fasting Mimicking Diet (FMD) to antibiotic-pretreated Parkinson’s Disease (PD) mice increased dopamine levels in the recipient PD mice, suggesting that gut microbiota contributed to the neuroprotection of FMD for PD (Feb 2019) https://link.springer.com/article/10.1007%2Fs13311-019-00719-2 Neuroprotection of Fasting Mimicking Diet on MPTP-Induced Parkinson’s Disease Mice via Gut Microbiota and Metabolites.
Neuroprotective effects of fecal microbiota transplantation on MPTP-induced Parkinson’s disease mice: Gut microbiota, glial reaction and TLR4/TNF-α signaling pathway (2018): https://www.sciencedirect.com/science/article/pii/S0889159118300175
Fecal microbiota transplantation protects rotenone-induced Parkinson’s disease mice via suppressing inflammation mediated by the lipopolysaccharide-TLR4 signaling pathway through the microbiota-gut-brain axis (Nov 2021) https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-021-01107-9
There's Mounting Evidence That Parkinson's Starts in The Gut - Not The Brain (Mar 2019): https://www.sciencealert.com/there-s-mounting-evidence-that-parkinson-s-starts-in-the-gut-not-the-brain
Does Parkinson’s Begin in the Gut? A growing body of evidence links the neurodegenerative disease to the gastrointestinal tract, opening new possibilities for treatment (May 2018): https://www.scientificamerican.com/article/does-parkinsons-begin-in-the-gut/
Antibiotic exposure and risk of Parkinson's disease in finland: A nationwide case‐control study (Nov 2019) https://onlinelibrary.wiley.com/doi/abs/10.1002/mds.27924 "Exposure to certain types of oral antibiotics seems to be associated with an elevated risk of PD with a delay that is consistent with the proposed duration of a prodromal period. The pattern of associations supports the hypothesis that effects on gut microbiota could link antibiotics to PD, but further studies are needed to confirm this"
The Parkinson’s disease gut has an overabundance of opportunistic pathogens. Overabundance of opportunistic pathogens is an original finding and a lead to test their role in PD. (Jun 2020, n=840) https://www.uab.edu/news/research/item/11389-the-parkinson-s-disease-gut-has-an-overabundance-of-opportunistic-pathogens Characterizing dysbiosis of gut microbiome in PD: evidence for overabundance of opportunistic pathogens.
Meta‐Analysis of Gut Dysbiosis in Parkinson's Disease (Jun 2020) https://onlinelibrary.wiley.com/doi/abs/10.1002/mds.28119 "intestinal mucin layer‐degrading Akkermansia is increased and short‐chain fatty acid–producing Roseburia and Faecalibacterium are decreased in PD across countries"
New study adds to growing body of evidence that Parkinson’s may start in the gut. Researchers found gut-to-brain propagation of alpha-synuclein spread via the vagus nerve. Transneuronal Propagation of Pathologic α-Synuclein from the Gut to the Brain Models Parkinson’s Disease (Jun 2019, mice) https://neurosciencenews.com/parkinsons-gut-14327/
The theory that Parkinson's disease can arise in the intestinal system and from there migrate to the brain has now gained support from new research, after seeing the disease migrate from the gut to the brain and heart of laboratory rats via the peripheral nerves https://health.au.dk/en/#news-16099. Evidence for bidirectional and trans-synaptic parasympathetic and sympathetic propagation of alpha-synuclein in rats (June 2019) https://link.springer.com/article/10.1007/s00401-019-02040-w
A gut-brain link for Parkinson’s gets a closer look. The misfolded proteins may start with microbes in the digestive system (Dec 2018): https://www.sciencenews.org/article/parkinsons-disease-gut-microbes-brain-link
Parkinsons disease and bacteriophages as its overlooked contributors (2018): https://www.nature.com/articles/s41598-018-29173-4
A specific gut bacterium directly induces PD symptoms and dopaminergic neuronal damage in the mouse brain (2018): https://www.nature.com/articles/s41598-018-19646-x
Gut microbiota are related to Parkinson's disease and clinical phenotype: https://onlinelibrary.wiley.com/doi/abs/10.1002/mds.26069 - https://www.prd-journal.com/article/S1353-8020(16)30323-6/abstract - https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-019-1528-y
Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson’s Disease (2016): https://archive.is/WaXjI || Good article coverage: https://scienceofparkinsons.com/2016/12/03/gut-reaction-to-parkinsons-disease/
PTSD:
PTSD could be prevented with gut microbes (2016): https://www.medicalnewstoday.com/articles/309600.php
Role of gut microbiome in posttraumatic stress disorder. The bacteria in your gut could hold clues to whether or not you will develop posttraumatic stress disorder (PTSD) after experiencing a traumatic event (2017): https://www.sciencedaily.com/releases/2017/10/171025103140.htm
Schizophrenia:
Review, 2020: The Gut Microbiome and Schizophrenia: The Current State of the Field and Clinical Applications https://www.frontiersin.org/articles/10.3389/fpsyt.2020.00156/full
Review, 2019: The gut microbiota promotes the pathogenesis of schizophrenia via multiple pathways https://www.sciencedirect.com/science/article/pii/S0006291X19303675
Review, 2018: Overview and systematic review of studies of microbiome in schizophrenia and bipolar disorder: https://www.journalofpsychiatricresearch.com/article/S0022-3956(17)31016-6/abstract
Review, 2017: The microbiome, immunity, and schizophrenia and bipolar disorder https://www.sciencedirect.com/science/article/pii/S0889159116305578
Transplantation of gut microbiota derived from patients with schizophrenia induces schizophrenia-like behaviors and dysregulated brain transcript response in mice (Apr 2024) https://forum.humanmicrobiome.info/threads/transplantation-of-gut-microbiota-derived-from-patients-with-schizophr.342/
From Infection to the Microbiome: An Evolving Role of Microbes in Schizophrenia (Mar 2019): https://link.springer.com/chapter/10.1007%2F7854_2018_84
Metagenome-wide association of gut microbiome features for schizophrenia (Mar 2020, n=171) https://www.nature.com/articles/s41467-020-15457-9 "Transplantation of a schizophrenia-enriched bacterium, Streptococcus vestibularis, appear to induce deficits in social behaviors, and alters neurotransmitter levels in peripheral tissues in recipient mice"
Altered gut microbiota associated with symptom severity in schizophrenia (n=82, July 2020) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7395597/
Transcriptome analysis in whole blood reveals increased microbial diversity in schizophrenia (2018): https://www.nature.com/articles/s41398-018-0107-9
The gut microbiome from patients with schizophrenia modulates the glutamate-glutamine-GABA cycle and schizophrenia-relevant behaviors in mice (2019): https://advances.sciencemag.org/content/5/2/eaau8317
Schizophrenia Linked with Abnormal Immune Response to Epstein-Barr Virus (2019): https://www.hopkinsmedicine.org/news/newsroom/news-releases/schizophrenia-linked-with-abnormal-immune-response-to-epstein-barr-virus
He Got Schizophrenia. He Got Cancer. And Then He Got Cured. (2018): https://www.nytimes.com/2018/09/29/opinion/sunday/schizophrenia-psychiatric-disorders-immune-system.html "man with leukemia received a bone-marrow transplant from a schizophrenic brother" https://archive.fo/oXUjP#selection-1959.1-1977.1
Case study: Bartonella and sudden-onset adolescent schizophrenia (Mar 2019): https://www.eurekalert.org/pub_releases/2019-03/ncsu-csb031819.php - https://doi.org/10.1177/1179573519832014
Bipolar disorder:
Review, 2018: Overview and systematic review of studies of microbiome in schizophrenia and bipolar disorder: https://www.journalofpsychiatricresearch.com/article/S0022-3956(17)31016-6/abstract
Review, 2017: The microbiome, immunity, and schizophrenia and bipolar disorder https://www.sciencedirect.com/science/article/pii/S0889159116305578
A case report looking at the effects of faecal microbiota transplantation in a patient with bipolar disorder (Mar 2020) https://journals.sagepub.com/doi/10.1177/0004867420912834 "Within 6 months of doing FMT, she was symptom free, and has remained symptom free [..] went from being functionally disabled to running a small business and has published two books". Via sci-hub, other details.