From Stool Transplants to Next-Generation Microbiota Therapeutics

Petrof, Elaine O.; Khoruts, Alexander

doi:10.1053/j.gastro.2014.01.004

Cited by 171 publications

(147 citation statements)

References 91 publications

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“…These findings indicate that IVS-1 not only had a higher affinity for GOS in vivo than the resident Bifidobacterium species but also utilized GOS to increase its competitiveness and effectively outcompete a closely related resident species. This finding is consistent with the niche exclusion model, which states that the organism most efficient at using limited nutrients outcompetes its competitors for the same niche (70). Strong inverse correlations between bifidobacteria and Clostridiaceae, Lactococcus, and Akkermansia (Fig.…”

Section: Discussionsupporting

confidence: 88%

In Vivo Selection To Identify Bacterial Strains with Enhanced Ecological Performance in Synbiotic Applications

Krumbeck

Maldonado-Gómez

Martínez

et al. 2015

Appl Environ Microbiol

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One strategy for enhancing the establishment of probiotic bacteria in the human intestinal tract is via the parallel administration of a prebiotic, which is referred to as a synbiotic. Here we present a novel method that allows a rational selection of putative probiotic strains to be used in synbiotic applications: in vivo selection (IVS). This method consists of isolating candidate probiotic strains from fecal samples following enrichment with the respective prebiotic. To test the potential of IVS, we isolated bifidobacteria from human subjects who consumed increasing doses of galactooligosaccharides (GOS) for 9 weeks. A retrospective analysis of the fecal microbiota of one subject revealed an 8-fold enrichment in Bifidobacterium adolescentis strain IVS-1 during GOS administration. The functionality of GOS to support the establishment of IVS-1 in the gastrointestinal tract was then evaluated in rats administered the bacterial strain alone, the prebiotic alone, or the synbiotic combination. Strain-specific quantitative real-time PCR showed that the addition of GOS increased B. adolescentis IVS-1 abundance in the distal intestine by nearly 2 logs compared to rats receiving only the probiotic. Illumina 16S rRNA sequencing not only confirmed the increased establishment of IVS-1 in the intestine but also revealed that the strain was able to outcompete the resident Bifidobacterium population when provided with GOS. In conclusion, this study demonstrated that IVS can be used to successfully formulate a synergistic synbiotic that can substantially enhance the establishment and competitiveness of a putative probiotic strain in the gastrointestinal tract.T he mechanistic role of the gastrointestinal (GI) microbiota and its metabolites in maintaining human health has been well demonstrated (1-3). Gut microbes provide several important benefits for their host, including provision of nutrients, development and maturation of the immune system, and protection against pathogens via colonization resistance (4). However, the gut microbiota may also contribute to obesity, inflammatory and autoimmune diseases, and other chronic disease states (5-7). Such diseases are often associated with compositional alterations in the fecal microbiota, a condition referred to as "dysbiosis" (8). Given that the presence of specific types of bacteria and their relative abundance within the gut are considered to affect host health, there is much interest in devising strategies that modulate gut microbiota composition and potentially redress disease-related dysbiotic patterns (9).Dietary approaches currently available to modulate the gut microbiota include prebiotics (10-12), fermentable fibers (13, 14), probiotics (or live biotherapeutics) (15), and synbiotics, which are a combination of a probiotic and a prebiotic (11, 16). According to Kolida and Gibson (16), synbiotics can be either complementary or synergistic. Complementary synbiotics consist of a probiotic and a prebiotic selected to independently confer benefits to the host. In contrast, sy...

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Section: Discussionsupporting

confidence: 88%

In Vivo Selection To Identify Bacterial Strains with Enhanced Ecological Performance in Synbiotic Applications

Krumbeck

Maldonado-Gómez

Martínez

et al. 2015

Appl Environ Microbiol

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“…The optimal time for microbial manipulation may be in early life, when immune development is occurring in concert with gut colonization. Patients with established IBD may, in fact, have missed the window of opportunity [132]. UC and CD are heterogeneous disorders, suggesting that microbial-based strategies may require the identification of responder subgroups.…”

Section: Faecal Microbiota Transplantationmentioning

confidence: 99%

The microbiota in inflammatory bowel disease

2015

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This review explores our current understanding of the complex interaction between environmental risk factors, genetic traits and the development of inflammatory bowel disease. The primacy of environmental risk factors is illustrated by the rapid increase in the incidence of the disease worldwide. We discuss how the gut microbiota is the proximate environmental risk factor for subsequent development of inflammatory bowel disease. The evolving fields of virome and mycobiome studies will further our understanding of the full potential of the gut microbiota in disease pathogenesis. Manipulating the gut microbiota is a promising therapeutic avenue.

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“…Second, synthetic probiotic mixtures represent a tailored treatment modality, since the profile of bacterial species can be selected based on specific criteria such as antimicrobial sensitivity patterns. Third, the formulation of a multi-species community derived from a selected ecosystem is more amenable to retaining the inherent characteristics of healthy gut microbiota necessary for robust colonization [99]. Furthermore, preparations of culture are more stable than fresh fecal suspensions, which are typically administered within 6 h of collection [74].…”

Section: Advantages Of Metmentioning

confidence: 99%

“…Standardized practices such as these can safeguard optimal large-scale manufacturing once FMT-based therapeutics becomes mainstream. Thus far, the University of Minnesota has established GMP production of FMT therapeutics [99]. The establishment of large-scale manufacturing of microbiota therapeutics will entail significant capital investment for facilities and personnel that are ultimately equipped to consistently produce diverse, healthy, and robust mixtures of intact bacterial communities.…”

Section: Challenges and Future Prospectsmentioning

confidence: 99%

Recurrent Clostridium difficile infection and the microbiome

2015

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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.

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From Stool Transplants to Next-Generation Microbiota Therapeutics

Cited by 171 publications

References 91 publications

In Vivo Selection To Identify Bacterial Strains with Enhanced Ecological Performance in Synbiotic Applications

In Vivo Selection To Identify Bacterial Strains with Enhanced Ecological Performance in Synbiotic Applications

The microbiota in inflammatory bowel disease

Recurrent Clostridium difficile infection and the microbiome

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