What is already known on this topic
Increased activation of specific immune cells and raised markers of inflammation are associated with negative health outcomes during ‘combination antiretroviral therapy’ (cART), a combination of drugs used to keep HIV infections under control. Scientists have known that microbial translocation into the blood can cause inflammation and immune reconstitution in people infected with HIV, but the underlying mechanisms remain unclear.
What this research adds
By following HIV-infected individuals for two years after cART initiation, researchers have detected changes in translocated constituents of the microbiota. Over the course of the first year, increased numbers of immune cells called CD4 T cell were associated with high levels of Serratia bacteria and pro-inflammatory immune molecules, which drive inflammation and a first wave of immune reconstitution. In the second year, reduced levels of Serratia and of inflammatory molecules were associated with immune reconstitution and CD4 T cell recovery. CD4 T cell recovery is a key measure of clinical outcome.
The results show that fecal microbiota transplants combined with daily fiber supplement improves insulin sensitivity in obese individuals with metabolic syndrome. If larger trials continue to show benefit, the approach could be used as a potential therapy within five years, the researchers say.
The rise in obesity and metabolic syndrome, a condition that can lead to diabetes, is one of the greatest health threats of the 21st century. Now, a small clinical trial shows that fecal microbiota transplants combined with daily fiber supplement improves insulin sensitivity — which can help reduce blood sugar — in obese individuals with metabolic syndrome.
The trial is the first of its kind to show that fecal transplantation is effective in people with obesity-related metabolic syndrome. The findings are published in Nature Medicine. “The potential for improving human health through the microbiome is immense,” says study senior author Karen Madsen at the University of Alberta. “We are only scratching the surface at the moment.”
Fecal microbiota transplants, during which stool from healthy donors is transferred to the gut of a sick person, have shown promise as treatment for recurrent bowel infections caused by the bacterium Clostridioides difficile. But whether fecal microbiota transplants can be used to treat other conditions such as metabolic disorders remains unclear.
Madsen and her colleagues enrolled in the trial 70 obese people with metabolic syndrome, which is characterized by insulin resistance, high blood glucose, high blood pressure and other complications. “These patients were on the best-known medications (for metabolic syndrome) and we could improve them further, which shows us there is an avenue for improvement by targeting these different pathways in the microbiome,” Madsen says.
Trial participants were randomly assigned to one of four groups: fecal microbiota transplants and high-fermentable fiber (FMT-HF), FMT and low-fermentable fiber (FMT-LF), placebo FMT and high-fermentable fiber (HF), and placebo FMT and low-fermentable fiber (LF). Of the 70 individuals enrolled in the trial, 61 completed their week-6 visit.
The stool donors for the study were four lean, healthy people. Fecal transplants were taken by mouth in a single dose of about 20 pills with no taste or odor.
After six weeks, individuals who received a fecal microbial transplant followed by a daily fiber supplement had better insulin sensitivity and higher levels of beneficial gut microbes than individuals who did not receive a fecal transplant. Improved insulin sensitivity can help to reduce blood sugar. “They were much more metabolically healthy,” Madsen says.
The type of fiber supplement following the transplant appeared to be key to the beneficial health outcome. While our bodies can’t break down fiber, healthy bacteria can obtain energy by degrading it. The team tested two types of fiber: fermentable fiber, which is found in beans and other foods, and non-fermentable fiber, which is found in whole grains.
After six weeks, individuals who received a non-fermentable fiber supplement had increased bacterial richness in their guts. The intervention led to changes in several bacterial genera, including increases in the levels of Phascolarcobacterium, Christensenellaceae, Bacteroides and Akkermansia muciniphila, and decreases in Dialister and Ruminococcus torques. Phascolarctobacterium and some Bacteroides species were associated with improved insulin sensitivity, the researchers found.
“Non-fermentable fiber can change gut motility — how fast things move through — as well as act as a bulking and binding agent that can change levels of bile acids, which could help explain our results,” Madsen says.
The researchers now plan to do a longer study with more participants to learn how fecal microbiota transplants combined with daily fiber supplement can improve health outcomes. If clinical trials continue to show benefit, fecal transplant pills could be available as a potential therapy within five years, Madsen says.