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Crosstalk between COVID-19 and the gut-brain axis: a gut feeling

Kalam N, Balasubramaniam VRMT

Postgrad Med J, 2024 Jul 18;100(1186):539-554.
PMID: 38493312 DOI: 10.1093/postmj/qgae030

The microbes in the gut are crucial for maintaining the body's immune system and overall gut health. However, it is not fully understood how an unstable gut environment can lead to more severe cases of SARS-CoV-2 infection. The gut microbiota also plays a role in the gut-brain axis and interacts with the central nervous system through metabolic and neuroendocrine pathways. The interaction between the microbiota and the host's body involves hormonal, immune, and neural pathways, and any disruption in the balance of gut bacteria can lead to dysbiosis, which contributes to pathogen growth. In this context, we discuss how dysbiosis could contribute to comorbidities that increase susceptibility to SARS-CoV-2. Probiotics and fecal microbiota transplantation have successfully treated infectious and non-infectious inflammatory-related diseases, the most common comorbidities. These treatments could be adjuvant therapies for COVID-19 infection by restoring gut homeostasis and balancing the gut microbiota.

Matched MeSH terms: Fecal Microbiota Transplantation*
Fecal microbiota transplantation: History, procedure and regulatory considerations

D T, Venkatesh MP

Presse Med, 2023 Dec;52(4):104204.
PMID: 37944641 DOI: 10.1016/j.lpm.2023.104204

Fecal microbiota transplantation (FMT) is a medical treatment which involves the transfer of feces from a healthy donor to a recipient to restore the balance of gut microbiota and improve clinical outcomes. FMT has gained recognition in recent years due to its effectiveness in treating recurrent Clostridioides difficile infections (rCDI) and other gastrointestinal disorders. Additionally, it has been studied as an intervention for some other conditions, like inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). This review covers regulatory considerations related to FMT, including the current state of FMT regulation and the need for further research to fully understand the safety and efficacy of this treatment. For transplantation of fecal microbiota, the Food and Drug Administration (FDA) classifies the treatment as an investigational new drug (IND), which typically requires physicians and scientists to submit an IND application. Ethical issues surrounding FMT, including the necessity of informed consent from donors and recipients and the potential transmission of infectious agents, are also discussed. Overall, FMT has the potential to offer significant therapeutic benefits, but it also raises regulatory and ethical considerations that require careful consideration. Further research is necessary to fully comprehend risks and benefits of FMT and to develop guidelines for its use in clinical practice.

Matched MeSH terms: Fecal Microbiota Transplantation/methods
A case report of improvement on ADHD symptoms after fecal microbiota transplantation with gut microbiome profiling pre- and post-procedure

Hooi SL, Dwiyanto J, Rasiti H, Toh KY, Wong RKM, Lee JWJ

Curr Med Res Opin, 2022 Nov;38(11):1977-1982.
PMID: 36164761 DOI: 10.1080/03007995.2022.2129232

BACKGROUND: Recent studies demonstrate the association of the gut microbiome in regulating interactions between the central nervous system and intestinal function. Individuals with attention-deficit hyperactivity disorder (ADHD) have been shown to have unique gut microbial signature, with depletion of beneficial commensal microbes. Fecal microbiota transplant (FMT) restores the imbalanced gut microbiome and may replete missing microbes to increase production of hormones and neurotransmitters regulating human behavior and cognition.
RESEARCH DESIGN & METHODS: Here, we present an interesting case of a 22-year-old woman treated with FMT primarily to treat recurrent Clostridioides difficile infection, which coincidentally alleviated her ADHD symptoms. We also present the pre- and post-FMT gut microbiota profiles conducted using shotgun metagenomic sequencing on the patient's fecal samples to thereby highlight potential microbial-associated mechanisms associated with the relief of ADHD symptoms.
RESULTS & CONCLUSIONS: Our case report provides preliminary evidence regarding the use of FMT in a patient with C. difficile and ADHD. We speculate that gut microbiome modulation, in particular the gain or loss of specific microbial species and pathways involving the metabolism of SCFAs, tryptophan and GABA, may merit further exploration as a potential therapeutic strategy for ADHD.

Matched MeSH terms: Fecal Microbiota Transplantation/methods
Parkinson's disease and the gastrointestinal microbiome

Lubomski M, Tan AH, Lim SY, Holmes AJ, Davis RL, Sue CM

J Neurol, 2020 Sep;267(9):2507-2523.
PMID: 31041582 DOI: 10.1007/s00415-019-09320-1

Recently, there has been a surge in awareness of the gastrointestinal microbiome (GM) and its role in health and disease. Of particular note is an association between the GM and Parkinson's disease (PD) and the realisation that the GM can act via a complex bidirectional communication between the gut and the brain. Compelling evidence suggests that a shift in GM composition may play an important role in the pathogenesis of PD by facilitating the characteristic ascending neurodegenerative spread of α-synuclein aggregates from the enteric nervous system to the brain. Here, we review evidence linking GM changes with PD, highlighting mechanisms supportive of pathological α-synuclein spread and intestinal inflammation in PD. We summarise existing patterns and correlations seen in clinical studies of the GM in PD, together with the impacts of non-motor symptoms, medications, lifestyle, diet and ageing on the GM. Roles of GM modulating therapies including probiotics and faecal microbiota transplantation are discussed. Encouragingly, alterations in the GM have repeatedly been observed in PD, supporting a biological link and highlighting it as a potential therapeutic target.

Matched MeSH terms: Fecal Microbiota Transplantation
Fulltext 2019 update of the WSES guidelines for management of Clostridioides (Clostridium) difficile infection in surgical patients

Sartelli M, Di Bella S, McFarland LV, Khanna S, Furuya-Kanamori L, Abuzeid N, et al.

World J Emerg Surg, 2019 02 28;14:8.
PMID: 30858872 DOI: 10.1186/s13017-019-0228-3

In the last three decades, Clostridium difficile infection (CDI) has increased in incidence and severity in many countries worldwide. The increase in CDI incidence has been particularly apparent among surgical patients. Therefore, prevention of CDI and optimization of management in the surgical patient are paramount. An international multidisciplinary panel of experts from the World Society of Emergency Surgery (WSES) updated its guidelines for management of CDI in surgical patients according to the most recent available literature. The update includes recent changes introduced in the management of this infection.

Matched MeSH terms: Fecal Microbiota Transplantation/methods; Fecal Microbiota Transplantation/trends
Gut Microbiota and Epilepsy: A Systematic Review on Their Relationship and Possible Therapeutics

Arulsamy A, Tan QY, Balasubramaniam V, O'Brien TJ, Shaikh MF

ACS Chem Neurosci, 2020 Nov 04;11(21):3488-3498.
PMID: 33064448 DOI: 10.1021/acschemneuro.0c00431

Dysbiosis of gut microbiota may lead to a range of diseases including neurological disorders. Thus, it is hypothesized that regulation of the intestinal microbiota may prevent or treat epilepsy. The purpose of this systematic review is to evaluate the evidence investigating the relationship between gut microbiota and epilepsy and possible interventions. A systematic review of the literature was done on four databases (PubMed, Scopus, EMBASE, and Web of Science). Study selection was restricted to original research articles while following the PRISMA guidelines. Six studies were selected. These studies cohesively support the interaction between gut microbiota and epileptic seizures. Gut microbiota analysis identified increases in Firmicutes, Proteobacteria, Verrucomicrobia, and Fusobacteria with decreases in Bacteroidetes and Actinobacteria in epileptic patients. Ketogenic diet, probiotics, and fecal microbiota transplantation (FMT) improved the dysbiosis of the gut microbiota and seizure activity. However, the studies either had a small sample size, lack of subject variability, or short study or follow-up period, which may question their reliability. Nevertheless, these limited studies conclusively suggest that gut microbiota diversity and dysbiosis may be involved in the pathology of epilepsy. Future studies providing more reliable and in depth insight into the gut microbial community will spark promising alternative therapies to current epilepsy treatment.

Matched MeSH terms: Fecal Microbiota Transplantation
Guidelines for microbiome studies in renal physiology

Muralitharan RR, Snelson M, Meric G, Coughlan MT, Marques FZ

Am J Physiol Renal Physiol, 2023 Sep 01;325(3):F345-F362.
PMID: 37440367 DOI: 10.1152/ajprenal.00072.2023

Gut microbiome research has increased dramatically in the last decade, including in renal health and disease. The field is moving from experiments showing mere association to causation using both forward and reverse microbiome approaches, leveraging tools such as germ-free animals, treatment with antibiotics, and fecal microbiota transplantations. However, we are still seeing a gap between discovery and translation that needs to be addressed, so that patients can benefit from microbiome-based therapies. In this guideline paper, we discuss the key considerations that affect the gut microbiome of animals and clinical studies assessing renal function, many of which are often overlooked, resulting in false-positive results. For animal studies, these include suppliers, acclimatization, baseline microbiota and its normalization, littermates and cohort/cage effects, diet, sex differences, age, circadian differences, antibiotics and sweeteners, and models used. Clinical studies have some unique considerations, which include sampling, gut transit time, dietary records, medication, and renal phenotypes. We provide best-practice guidance on sampling, storage, DNA extraction, and methods for microbial DNA sequencing (both 16S rRNA and shotgun metagenome). Finally, we discuss follow-up analyses, including tools available, metrics, and their interpretation, and the key challenges ahead in the microbiome field. By standardizing study designs, methods, and reporting, we will accelerate the findings from discovery to translation and result in new microbiome-based therapies that may improve renal health.

Matched MeSH terms: Fecal Microbiota Transplantation
Fulltext The Human Gut Microbiome - A Potential Controller of Wellness and Disease

Kho ZY, Lal SK

Front Microbiol, 2018;9:1835.
PMID: 30154767 DOI: 10.3389/fmicb.2018.01835

Interest toward the human microbiome, particularly gut microbiome has flourished in recent decades owing to the rapidly advancing sequence-based screening and humanized gnotobiotic model in interrogating the dynamic operations of commensal microbiota. Although this field is still at a very preliminary stage, whereby the functional properties of the complex gut microbiome remain less understood, several promising findings have been documented and exhibit great potential toward revolutionizing disease etiology and medical treatments. In this review, the interactions between gut microbiota and the host have been focused on, to provide an overview of the role of gut microbiota and their unique metabolites in conferring host protection against invading pathogen, regulation of diverse host physiological functions including metabolism, development and homeostasis of immunity and the nervous system. We elaborate on how gut microbial imbalance (dysbiosis) may lead to dysfunction of host machineries, thereby contributing to pathogenesis and/or progression toward a broad spectrum of diseases. Some of the most notable diseases namely Clostridium difficile infection (infectious disease), inflammatory bowel disease (intestinal immune-mediated disease), celiac disease (multisystemic autoimmune disorder), obesity (metabolic disease), colorectal cancer, and autism spectrum disorder (neuropsychiatric disorder) have been discussed and delineated along with recent findings. Novel therapies derived from microbiome studies such as fecal microbiota transplantation, probiotic and prebiotics to target associated diseases have been reviewed to introduce the idea of how certain disease symptoms can be ameliorated through dysbiosis correction, thus revealing a new scientific approach toward disease treatment. Toward the end of this review, several research gaps and limitations have been described along with suggested future studies to overcome the current research lacunae. Despite the ongoing debate on whether gut microbiome plays a role in the above-mentioned diseases, we have in this review, gathered evidence showing a potentially far more complex link beyond the unidirectional cause-and-effect relationship between them.

Matched MeSH terms: Fecal Microbiota Transplantation
Fulltext The Microbiome and Irritable Bowel Syndrome - A Review on the Pathophysiology, Current Research and Future Therapy

Chong PP, Chin VK, Looi CY, Wong WF, Madhavan P, Yong VC

Front Microbiol, 2019;10:1136.
PMID: 31244784 DOI: 10.3389/fmicb.2019.01136

Irritable bowel syndrome (IBS) is a functional disorder which affects a large proportion of the population globally. The precise etiology of IBS is still unknown, although consensus understanding proposes IBS to be of multifactorial origin with yet undefined subtypes. Genetic and epigenetic factors, stress-related nervous and endocrine systems, immune dysregulation and the brain-gut axis seem to be contributing factors that predispose individuals to IBS. In addition to food hypersensitivity, toxins and adverse life events, chronic infections and dysbiotic gut microbiota have been suggested to trigger IBS symptoms in tandem with the predisposing factors. This review will summarize the pathophysiology of IBS and the role of gut microbiota in relation to IBS. Current methodologies for microbiome studies in IBS such as genome sequencing, metagenomics, culturomics and animal models will be discussed. The myriad of therapy options such as immunoglobulins (immune-based therapy), probiotics and prebiotics, dietary modifications including FODMAP restriction diet and gluten-free diet, as well as fecal transplantation will be reviewed. Finally this review will highlight future directions in IBS therapy research, including identification of new molecular targets, application of 3-D gut model, gut-on-a-chip and personalized therapy.

Matched MeSH terms: Fecal Microbiota Transplantation
Fulltext A Revolutionizing Approach to Autism Spectrum Disorder Using the Microbiome

Johnson D, Letchumanan V, Thurairajasingam S, Lee LH

Nutrients, 2020 Jul 03;12(7).
PMID: 32635373 DOI: 10.3390/nu12071983

The study of human microbiota and health has emerged as one of the ubiquitous research pursuits in recent decades which certainly warrants the attention of both researchers and clinicians. Many health conditions have been linked to the gut microbiota which is the largest reservoir of microbes in the human body. Autism spectrum disorder (ASD) is one of the neurodevelopmental disorders which has been extensively explored in relation to gut microbiome. The utilization of microbial knowledge promises a more integrative perspective in understanding this disorder, albeit being an emerging field in research. More interestingly, oral and vaginal microbiomes, indicating possible maternal influence, have equally drawn the attention of researchers to study their potential roles in the etiopathology of ASD. Therefore, this review attempts to integrate the knowledge of microbiome and its significance in relation to ASD including the hypothetical aetiology of ASD and its commonly associated comorbidities. The microbiota-based interventions including diet, prebiotics, probiotics, antibiotics, and faecal microbial transplant (FMT) have also been explored in relation to ASD. Of these, diet and probiotics are seemingly promising breakthrough interventions in the context of ASD for lesser known side effects, feasibility and easier administration, although more studies are needed to ascertain the actual clinical efficacy of these interventions. The existing knowledge and research gaps call for a more expanded and resolute research efforts in establishing the relationship between autism and microbiomes.

Matched MeSH terms: Fecal Microbiota Transplantation

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