Non-alcoholic fatty liver disease is the liver’s version of metabolic dysfunction, and effective treatments are missing. passes undigested to the colon and feeds the microbiome, which makes it a candidate for a microbiota-directed intervention. So a four-month randomized placebo-controlled trial gave it to people with the condition, with metagenomics and metabolomics alongside. Did the liver fat move, and if so, how?
Liver fat fell by nine percentage points. Against 97 controls, the 99 people on resistant starch showed a 9.08 percent absolute reduction in , which was 5.89 percent after adjusting for weight loss. Serum and particular gut species, notably Bacteroides stercoris, correlated with liver fat and liver enzymes, and resistant starch reduced them. Mouse transplants supported the causal chain.
Non-alcoholic fatty liver disease is a hepatic manifestation of metabolic dysfunction, and effective interventions for it are lacking. Resistant starch is an unusual candidate, because it is not absorbed: it passes the small intestine intact and arrives in the colon, where the microbiome gets it. That makes it a microbiota-directed dietary supplement rather than a nutrient.
The study coupled a four-month randomized placebo-controlled clinical trial in individuals with the disease to metagenomics and metabolomics. The intervention arm had 99 participants against 97 people in the control arm, so the comparison is reasonably sized for a dietary trial with imaging endpoints.
Resistant starch produced a 9.08 percent absolute reduction in intrahepatic triglyceride content, which came to 5.89 percent after adjusting for weight loss. That adjustment is the number worth carrying: most of the effect remained once the weight change was accounted for, so this is not simply a weight-loss result in disguise.
The mechanism was then chased down. Serum branched-chain amino acids and specific gut microbial species, Bacteroides stercoris in particular, correlated with liver fat and with liver enzymes, and all were reduced by the intervention. Multi-omics analysis linked the microbiota changes to amino acid availability and to hepatic steatosis, with causality supported by fecal microbiota transplantation and in mice. Read the limits with it: liver fat is a surrogate, the causal evidence is murine, and four months is a short look at a slow disease.
wat. Four months of resistant starch took nine percentage points of fat out of the liver, and most of it was not explained by weight loss.
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The weight-adjusted figure is the interesting one. Over half the liver fat reduction survived adjustment for weight loss, which suggests the starch was doing something through the gut rather than simply making people lighter.
How do we know?
Ni and colleagues ran a four-month randomized placebo-controlled trial in people with fatty liver disease, coupled with metagenomics and metabolomics, and tested causality by fecal microbiota transplantation and monocolonization in mice.
What is still unknown
The outcome is liver fat on imaging, a surrogate for the cirrhosis and liver failure that matter clinically. The causal step runs through mice, not people, and four months is short for a liver disease measured in decades.
Learn something?
Where to next
How do bacteria in a mouse’s gut change the way it behaves?microbiomeWhat happens to a mouse raised with no gut bacteria at all?microbiome
How many bacteria are there really in your body per human cell?microbiome