Researchers believe they have identified two important microorganisms that cause multiple sclerosis.

Researchers have been searching the gut for bacteria in the microbiome that cause multiple sclerosis (MS) for decades. Two types of bacteria that hide in the small intestine are now clearly implicated by new evidence from a rare twin study.

Eisenbergiella tayi and Lachnoclostridium were identified as the most probable causes of the nerve-damaging condition in the study, which evaluated 81 pairs of genetically identical siblings.

The multinational research led by Dr. Anna Peters of Ludwig Maximilian University of Munich discovered a connection between these bacteria and human and mouse disease.

Analysing identical twins for hints

Since identical twins have almost all of the same genes, health disparities are frequently caused by external variables. The researchers eliminated a lot of genetic noise by concentrating on twins in which only one sibling had multiple sclerosis.

51 microbial possibilities were identified by in-depth DNA tracking of gut samples; the numbers of these varied between siblings who were afflicted and those who were not.

At the top of the watch list were two bacterial species that repeatedly surfaced with the greatest odds ratios.

The ileum, the final segment of the small intestine that houses a bustling immunological garrison, is where those samples originated. Because pro-inflammatory T cells congregate here before travelling to the brain and spinal cord, the decision was significant.

The same two bacterial species were found in a subsequent comparison with the 1,152-person International MS Microbiome Study. The Munich team was reassured by the overlap that their twin cohort was not a statistical anomaly.

Multiple sclerosis and gut bacteria

The researchers went beyond sequencing to test causality instead of correlation. In germ-free mice designed to develop inflammation similar to multiple sclerosis, they implanted ileal bacteria from selected twins.

Within twelve weeks, paralysis developed in rats that were exposed to microorganisms from the sibling who had multiple sclerosis. Throughout the whole investigation, mice that were given the healthy twin's microorganisms remained mobile.

In one experiment, E. Tayi bloomed dramatically in three female mice shortly before the onset of MS symptoms. Other frequent bacterial genera were absent from their faeces, suggesting that the bloom pushed out possible rivals.

Lachnoclostridium dominated late in the trial, and the results were replicated in a follow-up transfer from another twin pair. The signal was skewed towards female animals once more, which is consistent with women's increased risk of MS.

Overall, mice with "MS" bacteria experienced spinal lesions in over 60% of cases, while control groups experienced spinal lesions in less than 10% of cases. In every trial, no other single species increased in tandem with the sickness.

Inflammation and bacteria that break down fibre

Lachnoclostridium and E. tayi are members of the Lachnospiraceae family, a broad clan of anaerobes that typically aid in the digestion of fibre. The majority of relatives are seen as benign and even helpful.

Although the German study pointed out that both can flourish on mucus sugars when dietary fibre is limited, it is unclear what distinguishes these two. This capability might allow microbial compounds to reach immune sensors and weaken the intestinal barrier.

Previous research on Akkermansia muciniphila revealed a similar mucus-eating behaviour that can occasionally exacerbate inflammation. The latest study suggests that, although in a considerably smaller bacterial niche, the same process might be at work here.

Metabolic profiling also revealed that E. tayi generates succinate and ethanol, both of which are known to activate Th17 immune cells. Attacks on myelin, the insulating layer surrounding nerves, are caused by excessive Th17 activity.

The reasons why Lachnospiraceae could cause problems

Some Lachnospiraceae induced macrophages to adopt an aggressive posture in a model of controlled ulcerative colitis. The spinal cords of the colonised animals showed similar patterns of macrophages.

However, other research has documented anti-inflammatory functions for many family members, highlighting the fact that taxonomy is not fate. Results are influenced by the surrounding bacteria, gene content, and context.

Because both siblings inherit the same immunological genes, the twin study design suggests that the environment tips the scales. Antibiotics, diet, or past viral activity may provide the two microorganisms with the necessary foothold.

"When combined with our functional investigations, this bolsters our conclusion that these bacteria may be important environmental triggers for human multiple sclerosis," the researchers concluded.

Regarding the connection between gut bacteria and the onset of multiple sclerosis, the statement represents one of the most compelling causal arguments to date.

Treatment for Multiple Sclerosis Bacteria

Current medications only slow the progression of MS, which affects over one million Americans. It is easier to target two bacteria than to re-engineer the entire gut microbiome.

To target individual species in the gut, researchers are already using phage cocktails, tailored probiotics, and targeted antibiotics. Similar instruments could stop Lachnoclostridium or E. coli before they cause immunological problems.

Adding fibre to safer foods is another way to keep mucus eaters busy. Microbe-directed therapy may be supplemented by high-propionate diets, which have shown modest symptom improvement in early trials.

Restrictions and subsequent actions

Additionally, any treatment for multiple sclerosis must honour the larger ecosystem of gut microbes that promote immunological tolerance and vitamin production.

As demonstrated by the fact that broad antibiotics can exacerbate autoimmune flares, eliminating the incorrect bacterial strains may have unintended consequences.

Because of this risk, scientists are now looking into bacteriophages—viruses that hunt particular bacteria—which are already being studied in the early stages of inflammatory bowel disease.

Friendly neighbours could remain unaffected while the Lachnospiraceae perpetrators are reduced by a similar designer virus.

Authorities will require concrete evidence that modifying the microbiome affects biomarkers like neurofilament light, a blood protein that increases in response to neuronal death. Peters' twin-mouse pipeline now provides a means of rapidly gathering that evidence.

The speed at which these discoveries can be translated into medications will depend on the ongoing cooperation of neurologists, immunologists, and microbial ecologists.

For the time being, the findings provide patients with a concrete goal and a new motivation to be concerned about their gut health.