Study Unlocks Key Bacteria That Explains Why Only Some with IBD Respond to Thiamine

A new study discovered the presence of faecalibacterium prausnitzii and Roseburia hominis may determine whether a patient with chronic fatigue will respond well to thiamine treatment.¹

Patients with inflammatory bowel disease (IBD) often have chronic fatigue, most likely caused by microbial diversity and butyrate-producing bacteria which have been linked to the fatigue pathogenesis.

Vitamin B1, or thiamine, reduces fatigue for some patients with IBD but not all. This study provides insight into why high-dose thiamine only helps select patients regain their energy.

“We know that about half of the fatigued patients benefit from treatment with vitamin B1, but we haven't been able to find anything that distinguishes those who had an effect from those who did not,” said lead author Christian Lodberg Hvas, PhD, a professor and consultant at Aarthus University.² “Now we know that it's especially the bacterium Faecalibacterium prausnitzii (FP) that is the key.”

Investigators sought to investigate how the gut microbiota impacted how well high-dose thiamine worked in reducing chronic fatigue in patients with IBD.¹ Participants received both thiamine and placebo in 2 periods of 4 weeks with a break in the middle since investigators wanted to see if thiamine impacted fatigue.

The team analyzed the microbiota and short-chain fatty acid concentrations in fecal samples from patients with quiescent IBD who had (n = 40) or did not have (n = 20) chronic fatigue. The patients with quiescent IBD and fatigue were included in a randomized, placebo-controlled, crossover trial to evaluate a 4-week high-oral dose of thiamine treatment.

Butyrate and butyrate-producing bacteria had comparable levels in patients with and without fatigue. The levels did not change with high-dose thiamine treatment.

Conversely, Faecalibacterium prausnitzii was more prevalent in patients who responded well to thiamine compared with those who responded poorly, both pre-treatment (P = .019) and post-treatment (P = .038). The abundance of Faecalibacterium prausnitzii and Roseburia hominis were inversely correlated with IBD fatigue score changes among patients with chronic fatigue pre-treatment (P = .004) and post-treatment (P = .017).

“The bacterium is largely present in people with good health and only present in low numbers in people with chronic diseases,” Lodberg Hvas said.² “We don't know if it's just a marker for health or if it's part of the reason why healthy people are indeed healthy. But the more studies that point to a beneficial effect of FP, the more it suggests that the bacterium is involved as a cause of health and not just as a bystander.”

Ultimately, investigators were surprised to learn a single key bacterium determined whether patients with chronic fatigue responded well to thiamine treatment.

“We thought we were looking for a 'fatigue microbiome,' a composition of gut bacteria that is particularly seen in patients with chronic fatigue. But we didn't find that. Instead, we found that the microbiome of the fatigued largely resembles the microbiome of those who are not fatigued," Lodberg Hvas said.

The fatigue of patients with IBD had previously been unexplained and could not be eliminated by taking supplements for iron or vitamin D, like for other conditions. Now, people with unexplained fatigue have a potential treatment option. Investigators noted that 1 downside of high-dose thiamine as it has a peculiar smell and taste—a smell that will travel to hands, urine, and sweat. Other than that, thiamine does not cause any adverse events.

“We really want to help them, and although we don't have an explanation, we now have a cure – for those who have many [faecalibacterium prausnitzii] in their gut," Lodberg Hvas said. “Therefore, we now recommend high-dose vitamin B1 treatment to all our patients where we don't find any obvious explanation for chronic fatigue. We know that it only works for half, but it's still a good chance, and a month's treatment is cheap.”

References

1. ^{Bermúdez-Sánchez S, Bager P, Dahlerup JF, Baunwall SMD, Licht TR, Mortensen MS, Hvas CL, Thiamine-reduced fatigue in quiescent inflammatory bowel disease is linked to Faecalibacterium prausnitzii abundance, Gastro Hep Advances (2024), doi: https://doi.org/10.1016/ j.gastha.2024.08.012.}
2. ^{Vitamin B is an effective cure for many intestinal patients with chronic fatigue. EurekAlert! September 2, 2024. https://www.eurekalert.org/news-releases/1056434. Accessed September 5, 2024.}