Feasibility of fecal microbiota transplantation via oral gavage to safely alter gut microbiome composition in marmosets

Abstract

Disruption of microbial communities within human hosts has been associated with infection, obesity, cognitive decline, cancer risk and frailty, suggesting that microbiome-targeted therapies may be an option for improving healthspan and lifespan. The objectives of this study were to determine the feasibility of delivering fecal microbiota transplants (FMTs) to marmosets via oral gavage and to evaluate if alteration of the gut microbiome post-FMT could be achieved. This was a prospective study of marmosets housed at the Barshop Institute for Longevity and Aging Studies in San Antonio, Texas. Eligible animals included healthy young adult males (age 2-5 years) with no recent medication use. Stool from two donors was combined and administered in 0.5 ml doses to five young recipients once weekly for 3 weeks. Safety outcomes and alterations in the gut microbiome composition via 16S ribosomal RNA sequencing were compared at baseline and monthly up to 6 months post-FMT. Overall, significant differences in the percent relative abundance was seen in FMT recipients at the phylum and family levels from baseline to 1 month and baseline to 6 months post-FMT. In permutational multivariate analysis of variance analyses, treatment status (donor vs. recipient) (p = .056) and time course (p = .019) predicted β diversity (p = .056). The FMT recipients did not experience any negative health outcomes over the course of the treatment. FMT via oral gavage was safe to administer to young adult marmosets. The marmoset microbiome may be altered by FMT; however, progressive changes in the microbiome are strongly driven by the host and its baseline microbiome composition. K E Y W O R D S aging, fecal microbiota transplantation, gut microbiota, healthspan 1 | BACKGROUND In 2030, when the last baby boomer turns 65, one out of every five Americans (about 72 million people) will be 65 years or older (Centers for Disease & Prevention, 2003, 2015). This shift to an aged population is likely to increase overall economic burden, including costs of medical care and an increase in the percentage of the population not working (Dall et al., 2013; Weil, 1997). Due to the dynamic alteration of human population needs in the near future, aging researchers are no longer simply focused on extending human lifespan; they are interested in increasing quality of life, extending the length of time people are living independently, and overall healthspan for the aging population. Therefore, the focus of aging research has now shifted to treating aging as a systemic problem and determining whether an increase in lifespan alters the ability for that individual to remain disease free. The hope is that the treatment for multiple age-related diseases including diabetes, cardiovascular disease, Alzheimer's disease, dementia, and sarcopenia could be

Dual cognitive and mobility impairments and future dementia ‐ Setting a research agenda

“…Some non-pharmacological studies may prevent dual decline but empirical data are needed, such as transcranial direct current stimulation studies, 27 cognitive training, cognitive stimulation/engagement training, [28][29][30][31][32][33][34] blood pressure management, 35 dietary restriction, weight loss, and increased physical activity. 36,37 45 Preliminary results from the anti-amyloid antibody Lecanemab trial show positive effects on both primary and secondary outcomes of dementia. Whether these drug therapies prevent dual decline during aging remains unknown.…”

“…Understanding biological pathways is key to identifying therapeutic targets. Currently, microbiome‐mediated therapies are being examined for aging and healthspan in marmosets 45 . Preliminary results from the anti‐amyloid antibody Lecanemab trial show positive effects on both primary and secondary outcomes of dementia.…”

Bibliometric and visual analysis of fecal microbiota transplantation research from 2012 to 2021

“…Although extensive clinical studies have proved the safety of FMT ( Goloshchapov et al., 2019 ; Saha et al., 2021 ), a small number of patients undergoing FMT may suffer from adverse reactions such as abdominal pain, diarrhea ( Michailidis et al., 2021 ), recurrent infection, and even death ( Ser et al., 2021 ). Clinical guidelines are the evidence base for medical practice ( Kondylakis et al., 2020 ), and therefore, are important for guiding research and promotion of FMT ( Haifer et al., 2020 ), operating procedures ( Cammarota et al., 2019 ), and administration routes ( Ross and Reveles, 2020 ; Halaweish et al., 2022 ). At the policy and legislative levels, there is a need for both a flexible regulatory framework to promote the application and research, and traceability of fecal donors to ensure patient safety ( Vyas et al., 2015 ; Cammarota et al., 2019 ).…”

Frailty in kidney transplant candidates and recipients: pathogenesis and intervention strategies

“…Researchers have also used microflora to treat gut microbiota dysbiosis in perioperative KT recipients [99,100] . Fecal microbiota transplantation has been demonstrated to be feasible and effective in improving intestinal flora's composition and metabolism in animal experiments [101] . DeJong et al [102] pointed out that dietary intervention can increase intestinal microbial diversity and short-chain fatty acids (a microbial metabolite that is beneficial to improving frailty), thus reducing systemic inflammation.…”

“…[ 99 , 100 ] Fecal microbiota transplantation has been demonstrated to be feasible and effective in improving intestinal flora's composition and metabolism in animal experiments. [ 101 ] DeJong et al [ 102 ] pointed out that dietary intervention can increase intestinal microbial diversity and short-chain fatty acids (a microbial metabolite that is beneficial to improving frailty), thus reducing systemic inflammation. This research also suggested that supplementation with microbial metabolites lost in frail patients might be a more effective and safer method than direct microbiota transplantation.…”