Microbiota Therapies Research Articles

Clostridioides Difficile: A Concise Review of Best Practices and Updates.

Clostridioides difficile infection (CDI) is one of the most common and severe nosocomial infections worldwide. It can also affect healthy individuals in the community. The incidence of CDI has been on the rise globally for the past decade, necessitating a proactive approach to combat its spread; new strategies are being developed to enhance diagnostic accuracy and optimize treatment outcomes. Implementing the 2-step testing has increased diagnostic specificity, reducing the usage of CD-specific antibiotics with no concomitant increase in surgical complication rates. In 2021, the Infectious Diseases Society of America/Society for Healthcare Epidemiology of America (IDSA/SHEA) shifted its preference for initial treatment to fidaxomicin over vancomycin and metronidazole due to its lower recurrence rate. It also prioritized fidaxomicin for the treatment of recurrent CDI. There are new developments on the frontiers of fecal microbiota therapies, with RBX2660 and SER-109 approved recently by the FDA for prevention, with other microbiome-based therapies in various development and clinical trials. This review offers providers an updated and practical guide for CDI management.

A vanishing family of commensal bacteria and its impact on host health and disease

Abstract The gut microbiome plays a critical role in intestinal structure, immune homeostasis, and inflammatory diseases. The rise of these diseases in industrialized countries has been correlated with the loss of microbial diversity in the gut. One bacterial family, Muribaculaceae (Mb), is becoming a lost member in industrialized human microbiomes and many studies have correlated low Mb abundance with different disease states. Our goal is to determine how Mb depletion may be connected to disease, if introducing Mb back can ameliorate the impact of disease, and uncover immune mechanisms necessary for colonization of Mb. To study this, we developed two mouse models with complex microbiomes; one containing Mb (Mb positive), and one without Mb (Mb naïve). We evaluated intestinal structure with confocal microscopy, measured the production of short-chain fatty acids (SCFAs), and compared these mice in a Citrobacter rodentium (C. rodentium) infection model. Mice without Mb lost colonic mucus striation and had a significant drop in the production of SCFAs. Additionally, Mb positive mice had reduced C. rodentium colonization compared to mice lacking Mb. Lastly, we introduced 8 characterized Mb isolates to the Mb naïve mice to quantify immune responses by flow cytometry. We found that Mb is capable of establishing in Mb naïve mice, resulting in robust germinal centre B cell responses, yet no subsequent plasmablast accumulation in the mLN or lamina propria. Determining the mechanisms involved in disease amelioration by Mb and its impact on host immune responses is a novel research direction that could increase our understanding of colonization dynamics and highlights the potential of this bacteria as a model for microbiota therapies. Supported by grants from The W. Garfield Weston Foundation

Intrahost evolution of the gut microbiota.

A massive number of microorganisms, belonging to different species, continuously divide inside the guts of animals and humans. The large size of these communities and their rapid division times imply that we should be able to watch microbial evolution in the gut in real time, in a similar manner to what has been done in vitro. Here, we review recent findings on how natural selection shapes intrahost evolution (also known as within-host evolution), with a focus on the intestines of mice and humans. The microbiota of a healthy host is not as static as initially thought from the information measured at only one genomic marker. Rather, the genomes of each gut-colonizing species can be highly dynamic, and such dynamism seems to be related to the microbiota species diversity. Genetic and bioinformatic tools, and analysis of time series data, allow quantification of the selection strength on emerging mutations and horizontal transfer events in gut ecosystems. The drivers and functional consequences of gut evolution can now begin to be grasped. The rules of this intrahost microbiota evolution, and how they depend on the biology of each species, need to be understood for more effective development of microbiota therapies to help maintain or restore host health.

Faecal microbiota transplants: towards a healthy disgust scepticism

This paper engages with the obstacle of disgust surrounding the use of faecal microbiota transplants (FMT). In discourse about the human microbiome and microbiota-based therapies (like FMT), disgust has become...

How the Physical Environment Shapes the Microbiota.

ABSTRACTLiving systems, from micro- to macro-scales, are strongly impacted by physical factors such as temperature, pH, and the concentration of compounds in their surrounding environment. In the macro-world, it is obvious that small changes in these parameters can have profound, and even devastating, impacts on an ecosystem. For example, in the case of global warming, a change in climate, and specifically a few degrees in temperature, has taken one million species of animals to the brink of extinction. Scale things down 6 orders of magnitude, our gut microbiota also experiences similar changes in temperature due to disease. In this highly competitive environment, physical perturbations inflict long-term consequences on the microbiota ecosystem and, in turn, on the host organism. My laboratory is exploring the feedback between the gut’s physical environment, the microbiota, and disease. Our research highlights the importance of measuring physical parameters for the prediction of microbial dynamics and microbiota therapies.

Spotted around the web: Microbiota therapies, face processing in autism, Ninja Training

Spotted around the web: Microbiota therapies, face processing in autism, Ninja Training

The impact of early-life sub-therapeutic antibiotic treatment (STAT) on excessive weight is robust despite transfer of intestinal microbes

The high-fat, high-calorie diets of westernized cultures contribute to the global obesity epidemic, and early life exposure to antibiotics may potentiate those dietary effects. Previous experiments with mice had shown that sub-therapeutic antibiotic treatment (STAT)—even restricted to early life—affected the gut microbiota, altered host metabolism, and increased adiposity throughout the lifetime of the animals. Here we carried out a large-scale cohousing experiment to investigate whether cohousing STAT and untreated (Control) mice would transfer the STAT-perturbed microbiota and transmit its impact on weight. We exposed pregnant dams and their young offspring to either low-dose penicillin (STAT) or water (Control) until weaning, and then followed the offspring as they grew and endured a switch from normal to high-fat diet at week 17 of life. Cohousing, which started at week 4, rapidly approximated the microbiota within cages, lowering the weight of STAT mice relative to non-cohoused mice. The effect, however, varied between cages, and was restricted to the first 16 weeks when diet consisted of normal chow. Once mice switched to high-fat diet, the microbiota α- and β-diversity expanded and the effect of cohousing faded: STAT mice, again, were heavier than control mice independently of cohousing. Metabolomics revealed serum metabolites associated with STAT exposure, but no significant differences were detected in glucose or insulin tolerance. Our results show that cohousing can partly ameliorate the impact of STAT on the gut microbiota but not prevent increased weight with high-fat diet. These observations have implications for microbiota therapies aimed to resolve the collateral damage of antibiotics and their load on human obesity.

Current understanding of microbiota- and dietary-therapies for treating inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a result of chronic inflammation caused, in some part, by dysbiosis of intestinal microbiota, mainly commensal bacteria. Gut dysbiosis can be caused by multiple factors, including abnormal immune responses which might be related to genetic susceptibility, infection, western dietary habits, and administration of antibiotics. Consequently, the disease itself is characterized as having multiple causes, etiologies, and severities. Recent studies have identified >200 IBD risk loci in the host. It has been postulated that gut microbiota interact with these risk loci resulting in dysbiosis, and this subsequently leads to the development of IBD. Typical gut microbiota in IBD patients are characterized with decrease in species richness and many of the commensal, and beneficial, fecal bacteria such as Firmicutes and Bacteroidetes and an increase or bloom of Proteobacteria. However, at this time, cause and effect relationships have not been rigorously established. While treatments of IBD usually includes medications such as corticosteroids, 5-aminosalicylates, antibiotics, immunomodulators, and anti-TNF agents, restoration of gut dysbiosis seems to be a safer and more sustainable approach. Bacteriotherapies (now called microbiota therapies) and dietary interventions are effective way to modulate gut microbiota. In this review, we summarize factors involved in IBD and studies attempted to treat IBD with probiotics. We also discuss the potential use of microbiota therapies as one promising approach in treating IBD. As therapies based on the modulation of gut microbiota becomes more common, future studies should include individual gut microbiota differences to develop personalized therapy for IBD.

Gut Microbiota in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis: Current Applications and Future Perspectives.

The gut environment and gut microbiome dysbiosis have been demonstrated to significantly influence a range of disorders in humans, including obesity, diabetes, rheumatoid arthritis, and multiple sclerosis (MS). MS is an autoimmune disease affecting the central nervous system (CNS). The etiology of MS is not clear, and it should involve both genetic and extrinsic factors. The extrinsic factors responsible for predisposition to MS remain elusive. Recent studies on MS and its animal model, experimental autoimmune encephalomyelitis (EAE), have found that gastrointestinal microbiota may play an important role in the pathogenesis of MS/EAE. Thus, gut microbiome adjustment may be a future direction of treatment in MS. In this review, we discuss the characteristics of the gut microbiota, the connection between the brain and the gut, and the changes in gut microbiota in MS/EAE, and we explore the possibility of applying microbiota therapies in patients with MS.

Optimisation of 16S rRNA gut microbiota profiling of extremely low birth weight infants

BackgroundInfants born prematurely, particularly extremely low birth weight infants (ELBW) have altered gut microbial communities. Factors such as maternal health, gut immaturity, delivery mode, and antibiotic treatments are associated with microbiota disturbances, and are linked to an increased risk of certain diseases such as necrotising enterocolitis. Therefore, there is a requirement to optimally characterise microbial profiles in this at-risk cohort, via standardisation of methods, particularly for studying the influence of microbiota therapies (e.g. probiotic supplementation) on community profiles and health outcomes. Profiling of faecal samples using the 16S rRNA gene is a cost-efficient method for large-scale clinical studies to gain insights into the gut microbiota and additionally allows characterisation of cohorts were sample quantities are compromised (e.g. ELBW infants). However, DNA extraction method, and the 16S rRNA region targeted can significantly change bacterial community profiles obtained, and so confound comparisons between studies. Thus, we sought to optimise a 16S rRNA profiling protocol to allow standardisation for studying ELBW infant faecal samples, with or without probiotic supplementation.MethodsUsing ELBW faecal samples, we compared three different DNA extraction methods, and subsequently PCR amplified and sequenced three hypervariable regions of the 16S rRNA gene (V1 + V2 + V3), (V4 + V5) and (V6 + V7 + V8), and compared two bioinformatics approaches to analyse results (OTU and paired end). Paired shotgun metagenomics was used as a ‘gold-standard’.ResultsResults indicated a longer bead-beating step was required for optimal bacterial DNA extraction and that sequencing regions (V1 + V2 + V3) and (V6 + V7 + V8) provided the most representative taxonomic profiles, which was confirmed via shotgun analysis. Samples sequenced using the (V4 + V5) region were found to be underrepresented in specific taxa including Bifidobacterium, and had altered diversity profiles. Both bioinformatics 16S rRNA pipelines used in this study (OTU and paired end) presented similar taxonomic profiles at genus level.ConclusionsWe determined that DNA extraction from ELBW faecal samples, particularly those infants receiving probiotic supplementation, should include a prolonged beat-beating step. Furthermore, use of the 16S rRNA (V1 + V2 + V3) and (V6 + V7 + V8) regions provides reliable representation of ELBW microbiota profiles, while inclusion of the (V4 + V5) region may not be appropriate for studies where Bifidobacterium constitutes a resident microbiota member.

Recurrent Clostridium difficile infection and the microbiome.

The diverse and densely populated gastrointestinal microbiota is essential for the regulation of host physiology and immune function. As our knowledge of the composition and function of the intestinal microbiota continues to expand, there is new interest in using these developments to tailor fecal microbiota transplantation (FMT) and microbial ecosystem therapeutics (MET) for a variety of diseases. The potential role of FMT and MET in the treatment of Clostridium difficile infection (CDI)-currently the leading nosocomial gastrointestinal infection-has proven highly effective for recurrent CDI, and has emerged as a paradigm shift in the treatment of this disease. The current review will serve as a summary of the key aspects of CDI, and will introduce the essential framework and challenges of FMT, as is currently practiced. MET represents the progression of conventional bacteriotherapy that fundamentally capitalizes on the restorative properties of intestinal bacterial communities and may be viewed as the culmination of a rationally designed therapeutic modality. As our understanding of the composition and function of the intestinal microbiota evolves, it will likely drive next-generation microbiota therapies for a range of medical conditions, such as inflammatory bowel disease, obesity, and metabolic syndrome.

The gut microbiota and inflammatory noncommunicable diseases: Associations and potentials for gut microbiota therapies

The gut microbiota and inflammatory noncommunicable diseases: Associations and potentials for gut microbiota therapies

The Gut Microbiome in Health and Disease

The Gut Microbiome in Health and Disease