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Page 10 of 20 Manrique et al. Microbiome Res Rep 2024;3:23 https://dx.doi.org/10.20517/mrr.2023.80

Figure 3. Schematic representation of 2nd Generation microbiome-based therapeutic approaches: Microbiome-based therapies can be
divided into donor-based or donor-independent approaches. Donor-based approaches depend on the need for the donation of fecal
material to produce the final therapeutic product. Donor-based approaches require the donation of fecal samples from individuals, which
harbor a complex, non-standardized microbial community, and are subject to more intricate regulatory guidelines. On the other hand,
LBPs are donor-independent microbiome-based products that consist of a single strain or standardized microbial consortia associated
with the gut microbiome that have proven therapeutic effects in clinical trials. LBPs: Live biotherapeutic products.

gastric tubing [135,136] . Meta-analyses have shown that, among these, colonoscopy is the most effective mode of
delivery, with no significant differences compared to oral administration (> 80% overall) [132,137,138] .
Importantly, the upper delivery method has shown additional advantages in treating immune-related
disease, likely due to immune regulation in the small intestine [127,139] .

Because FMT requires administration by medical staff, and the effectivity using enemas has been variable,
public organizations and biotech companies are developing non-invasive, safe, and efficacious alternatives
[Figure 3]. The use of oral capsules containing donor-derived lyophilized fecal material has proven to be
[140]
almost as efficient as traditional FMT . Moreover, to make more sanitary products and decrease the
possibility of transferring undesired pathogens or toxic metabolites, companies are creating purified whole
microbial ecosystem products.

Therapies not dependent on stool donations are being developed to overcome one of the major bottlenecks
in the production of microbiota-based therapies - the availability of donated fecal material. Standardized
microbiome-based products can range from multi-species consortia composed of microorganisms from
different taxa, which provide general functions covered by the microbiota, to single-species products that
are able to regulate very specific functions. We consider this type of standardized microbiome-based
therapy as LBPs therapeutics (see discussion above), and currently, there are no LBPs (as standardized
single or mix consortia) approved yet.

To support the development of complex microbiome-based therapies, the existence of stool banks is
increasing worldwide . Similar to how organ donations work, stool banks can coordinate donations from
[141]
healthy individuals, perform thorough donor and sample screening to ensure product safety, store samples
in adequate conditions, and provide the material to companies developing such products upon request.
Moreover, banks can store individual samples on demand as a safety copy of their own microbiota, to have
the option of receiving an autologous FMT treatment if desired in the future [Figure 1]. In spite of certain