Fecal Microbiota Transplantation Improves Cognition in Older C. Difficile Patients
Fecal microbiota transplantation from young individuals to old individuals reduces inflammation, improves health, and extends life span in killifish, a short lived species. It at least reduces inflammation and improves health in mice. Despite being used to treat C. Difficile infections, in which the gut microbiome is overtaken by that unwelcome species of bacteria, there is next to no data in humans on the very interesting question of whether the gut microbiome, and the many declines in health that are associated with age-related shifts in the microbiome, can be improved by transplanting a sample of youthful gut microbes.
The study reported in today's open access paper doesn't help in providing an answer, I think. It is good to see that old people with C. Difficile infections resistant to other treatments can be helped by fecal microbiota transplantation. It is good to see that the patients experience improved cognitive function. But one can't separate the unpleasant effects of C. Difficile from the unpleasant effects of gut microbiome aging in this small study in that respect, and the choice of antibiotics for a control group, who were actually worse off after the treatment, just muddies the water, given the effects of antibiotics on the broader gut microbiome. The outcomes do not allow us to say all that much about how healthy older humans will benefit from the transplantation of a young gut microbiome, other than it appears safe to undertake.
In particular, we might look at chronic inflammation as one of the more relevant outcomes of gut microbiome aging. Inflammatory populations expand in number, perhaps because they are no longer adequately restrained by the immune system as it ages into immunosenescence. Chronic inflammation is strongly implicated in the progression of neurodegeneration and cognitive decline. Runaway C. Difficile infection is a highly inflammatory condition, however. Thus getting rid of the C. Difficile population obscures the question of whether and how the transplant is also improving the gut microbiome more generally in these older patients.
After fecal microbiota transplantation (FMT) to treat Clostridioides difficile infection (CDI), cognitive improvement is noticeable, suggesting an essential association between the gut microbiome and neural function. Although the gut microbiome has been associated with cognitive function, it remains to be elucidated whether fecal microbiota transplantation can improve cognition in patients with cognitive decline.
The study included 10 patients (age range, 63-90 years; female, 80%) with dementia and severe CDI who were receiving FMT. Also, 10 patients (age range, 62-91; female, 80%) with dementia and severe CDI who were not receiving FMT. They were evaluated using cognitive function tests (Mini-Mental State Examination [MMSE] and Clinical Dementia Rating scale Sum of Boxes [CDR-SB]) at 1 month before and after FMT or antibiotics treatment (control group). The patients' fecal samples were analyzed to compare the composition of their gut microbiota before and 3 weeks after FMT or antibiotics treatment.
Ten patients receiving FMT showed significantly improvements in clinical symptoms and cognitive functions compared to control group. The MMSE and CDR-SB of FMT group were improved compare to antibiotics treatment (MMSE: median 16.00 vs 10.0; CDR-SB: median 5.50 vs 8.0). FMT led to changes in the recipient's gut microbiota composition, with enrichment of Proteobacteria and Bacteroidetes. Alanine, aspartate, and glutamate metabolism pathways were also significantly different after FMT.
This study revealed important interactions between the gut microbiome and cognitive function. Moreover, it suggested that FMT may effectively delay cognitive decline in patients with dementia.