Deconfounded quantitative microbiome profiling in 228 MS patients and 2860 controls identified robust MS gut microbiome markers including lowered Bacteroides and higher Blautia and Methanobrevibacter, while demonstrating that commonly reported markers like Akkermansia and Roseburia are not confirmed after proper confounder control.
Total bacterial load was lower in relapsing-remitting MS patients compared to controls.
Strong fecal moisture effects indicative of longer intestinal transit times were observed in MS versus FGFP controls, driven primarily by primary progressive MS.
Applying deconfounded QMP identified 21 differentially abundant genera in MS patients compared to controls.
Meta-analysis of deconfounded QMP across 10 published studies did not confirm commonly reported MS microbiome markers Akkermansia and Roseburia.
Lowered Bacteroides, higher Blautia, and higher Methanobrevibacter emerged as robust MS biomarkers across the deconfounded meta-analysis.
Enterotype stratification linked the low cell count Bacteroides 2 enterotype to low-efficacy disease-modifying therapies (DMTs) and the Prevotella enterotype to lower disease severity.
Serum glial fibrillary acidic protein (GFAP), a biomarker of disease progression, was identified as a covariate of gut microbial variation in MS.
Confounder control and quantitative microbiome profiling substantially altered the identification of MS-associated microbiome markers compared to conventional relative abundance approaches.
This research suggests that previous studies on gut bacteria in multiple sclerosis (MS) have produced inconsistent results largely because they failed to account for important confounding factors — particularly how much water is in stool (a proxy for how quickly food moves through the gut) and the total number of bacteria present. By using a more rigorous approach called quantitative microbiome profiling (QMP) and controlling for these confounders in a large dataset of 228 MS patients and 2860 healthy controls, the researchers identified 21 bacterial groups that differ between MS patients and healthy people. They also re-analyzed data from 10 previously published studies (over 1,900 participants total) and found that some bacteria frequently reported as MS markers — including Akkermansia and Roseburia — do not hold up as robust markers once confounders are properly addressed. Instead, lower levels of Bacteroides and higher levels of Blautia and Methanobrevibacter emerged as more reliable indicators across studies. The study also found that different patterns of gut bacterial communities (called enterotypes) were linked to different aspects of MS — one community type was associated with use of less potent MS medications, while another was associated with milder disease. Additionally, the researchers discovered that blood levels of a brain injury protein called GFAP — used to track MS disease progression — were inversely correlated with the abundance of beneficial gut bacteria Faecalibacterium and Roseburia in patients with the progressive form of MS, suggesting a potential connection between gut health and neurological damage. This research suggests that the gut microbiome in MS is genuinely altered, but the specific changes are more nuanced than previously thought, and earlier studies may have been misled by differences in bowel habits and bacterial density between patients and controls. The findings highlight the importance of using rigorous, quantitative methods and careful confounder control in microbiome research, and point to specific bacterial targets — including butyrate-producing bacteria like Butyricicoccus and Butyricimonas — that warrant further investigation as potentially relevant to MS biology.
Pauwels A, Devolder L, Falony G, D'haeseleer M, Nagels G, Van Remoortel A, et al.. (2026). Deconfounded, quantitative microbiome profiling identifies robust multiple sclerosis markers and clinical covariate associations.. Gut microbes. https://doi.org/10.1080/19490976.2026.2681876