Aging of the Gut Microbiome Contributes to Severity of Sepsis
Sepsis is not, strictly speaking, an age-related condition. It can occur at any age, the result of bacterial infection leading to a feedback loop of runaway inflammatory signaling. Older individuals exhibit greater risk and greater severity of sepsis, however. The aged tissue environment and immune system is biased towards greater inflammation, and the immune system is less able to control bacterial infections. Given an infection leading towards sepsis, an older individual is less able to resist suffering a worse outcome. Senescent cells provide one contribution to the chronic inflammation of aging, but as noted here, changes in the gut microbiome are also a factor.
Older adults suffer more frequent and worse outcomes from sepsis, a critical illness secondary to infection. The reasons underlying this unique susceptibility are incompletely understood. Prior work in this area has focused on how the immune response changes with age. The current study, however, focuses instead on alterations in the community of bacteria that humans live with within their gut (i.e., the gut microbiome). The central concept of this paper is that the bacteria in our gut evolve along with the host and "age," making them more efficient at causing sepsis.
Prior research has focused on host factors as mediators of exaggerated sepsis-associated morbidity and mortality in older adults. This focus on the host, however, has failed to identify therapies that improve sepsis outcomes in the elderly. We hypothesized that the increased susceptibility of the aging population to sepsis is not only a function of the host but also reflects longevity-associated changes in the virulence of gut pathobionts.
We utilized two complementary models of gut microbiota-induced experimental sepsis to establish the aged gut microbiome as a key pathophysiologic driver of heightened disease severity. Further murine and human investigations into these polymicrobial bacterial communities demonstrated that age was associated with only subtle shifts in ecological composition but also an overabundance of genomic virulence factors that have functional consequence on host immune evasion. Escape of these age-conditioned pathogens from the intestinal lumen therefore leads to exaggerated sepsis severity.
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https://www.fda.gov/vaccines-blood-biologics/vowst
The FDA news release noted that the drug was part of an application designated for a rapid review aimed at getting products to market quickly and was granted Priority Review, Breakthrough Therapy, and Orphan designations.
According to the FDA news release, in a U.S. and Canadian randomized, double-blind, placebo-controlled, clinical study of the safety of Vowst, 89 participants received Vowst and 93 received placebo treatment. CDI recurrence in Vowst-treated participants was 12.4 percent, compared to 39.9 percent in placebo-treated participants. The FDA also reported that Vowst recipients were more likely to report abdominal bloating, fatigue, constipation, chills, and diarrhea after treatment.
The donated human fecal matter is screened for transmissible pathogens before it is manufactured. However, as the news release pointed out, there is a possibility that donor stool used in the pill could be infected with infectious pathogens, as well as food allergens. The potential for adverse reactions caused by Vowst due to such allergens is unknown.
There's no FDA-approved screening test for COVID-19 on the donor samples, so it's incumbent on the companies that collect donor stool and process it for transplants to do their own testing.
As sepsis is caused by runaway inflammation starting with a blood infection I thought I would point out that in the last 10 years research has shown that A. most Americans and Europeons are somewhat deficent in vitamin D3. B.Proper levels of this vitamin seem to have a modulating effect on inflammation due to infections so that the immune system does not over-react to infections. Could this be part of the reason that older people have a bigger problem with sepsis? Sepsis does strike younger people too and they also are likely to have low vitamin D because modern people spend way less time in the sun than our ancestors did.