For years, researchers have explored the gut microbiome for bacteria that might influence the immune system in relation to multiple sclerosis (MS). A recent twin study has now identified two specific bacteria residing in the small intestine as potential culprits.
In this study, scientists analyzed 81 sets of identical twins, pinpointing Eisenbergiella tayi and Lachnoclostridium as likely candidates for triggering this debilitating condition.
The research team from Ludwig Maximilian University of Munich, led by Dr. Anna Peters, connected these bacterial species to MS occurrences in both humans and mice.
Identical Twins: A Clue to the Mystery
Given that identical twins share nearly identical genetics, the variations in health observed can often be attributed to external influences. By focusing on pairs where only one twin was affected by MS, researchers minimized genetic noise.
They conducted a thorough DNA analysis of gut samples, identifying 51 microbial candidates that showed differing levels between affected and unaffected siblings. Notably, two bacteria were consistently linked with higher odds of the disease, placing them at the forefront of investigation.
The samples came from the ileum, the latter part of the small intestine, which plays a crucial role in immune response as it’s where pro-inflammatory T cells gather before attacking the brain and spinal cord.
When the study’s findings were compared with data from the larger International MS Microbiome Study involving over a thousand participants, the same two bacterial species emerged, lending further credibility to the results.
Gut Bacteria and Multiple Sclerosis
To investigate causation rather than mere correlation, researchers went beyond analysis and transferred ileal microbes from selected twins into germ-free mice known to develop MS-like inflammation.
Mice receiving bacteria from the MS-affected twin displayed signs of paralysis within twelve weeks, while those given microbes from the healthy sibling remained unaffected. In one experiment, three female mice exhibited a surge of E. tayi prior to the onset of symptoms, suggesting it outcompeted other beneficial bacteria.
Similar outcomes arose from another pair of twins, this time with Lachnoclostridium becoming more prevalent as the trial progressed. Interestingly, the trend toward females aligned with the higher MS risk seen in women.
Overall, over 60% of mice that received “MS” bacteria developed spinal lesions, compared to less than 10% in control groups, marking a significant result.
Linking Fiber-Digesting Bacteria with Inflammation
Both E. tayi and Lachnoclostridium belong to the Lachnospiraceae family, which generally aids in fiber digestion. While most relative species are harmless or beneficial, the distinction of these two remains uncertain.
However, researchers noted that both can thrive on mucosal sugars, particularly when dietary fiber is lacking. This could weaken the intestinal barrier and expose the immune system to harmful microbes.
Moreover, previous studies showed that another bacterium, Akkermansia muciniphila, also increased inflammation when consuming mucus. It appears this same phenomenon could apply here, albeit in a much narrower bacterial environment.
Metabolic profiling further revealed that E. tayi produces compounds like ethanol and succinate known to activate damaging Th17 immune cells, which can impede myelin, the protective layer of nerves.
Why Lachnospiraceae May Cause Issues
In a controlled model for ulcerative colitis, certain Lachnospiraceae strains prompted immune cells toward aggressive action. Similar behaviors were noted in the spinal cords of affected mice.
However, not all family members have been shown to exacerbate inflammation; some even exhibit anti-inflammatory properties, indicating that context and microbial composition matter significantly.
The design of the twin study implies that environmental factors influence outcomes, even when both siblings share the same immune genetics. Dietary habits, antibiotic use, and past viral infections may provide the needed advantage to these microbes.
The researchers concluded that this evidence supports the notion that these bacteria could be critical environmental triggers of human MS.
Treatment Avenues for Multiple Sclerosis
There are nearly a million individuals in the US living with MS, and current treatments focus on slowing disease progression. By targeting specific bacteria, addressing the issue may prove more manageable than altering the entire gut microbiome.
Researchers are already experimenting with narrow antibiotics, phage cocktails, and custom probiotics to tackle individual gut species, suggesting similar approaches could help in controlling E. tayi and Lachnoclostridium before they incite immune responses.
Alternatively, increasing fiber intake could also help alleviate the issue by keeping these bacteria busy with safer food options. Initial trials of high-fiber diets have shown modest improvement in symptoms and could dovetail well with microbe-targeted therapies.
Challenges Ahead and Future Directions
Any approach to treating MS will need to consider the broader community of gut bacteria that contribute to vitamin synthesis and immune system balance.
Removing the wrong strains might have counterproductive effects, as broad-spectrum antibiotics can sometimes trigger autoimmune flare-ups.
This concern has led researchers to explore bacteriophages—viruses that target specific bacteria—which are already being investigated for inflammatory bowel diseases. A custom phage could eliminate the problematic Lachnospiraceae while preserving beneficial strains.
Regulators will require solid evidence that modifying the microbiome can directly influence biomarkers like neurofilament light, which indicates neuron damage. The twin-mouse approach introduced by Peters offers a viable pathway to gather such proof quickly.
Collaboration among neurologists, immunologists, and microbial ecologists will be essential in transforming these findings into viable treatments.
For now, the results provide patients with a clearer target and a renewed interest in their gut microbiome’s inhabitants.
The findings have been published in PNAS.
