Bugs ‘n’ Guts

By September 29, 2017Homepage, Research News

The notion of a gut/brain connection is not a new one (in 1981 there was an international symposium in Florence, Italy on “The Gut-Brain Axis: A New Frontier”), but within the last few years evidence has been rapidly accumulating on the profound effects that our gut microbiomes have on our health and well-being. It has been a particularly hot topic of study in relation to autoimmune diseases, including multiple sclerosis (MS).

What is the microbiome? It’s the total population of microorganisms that we are host to, from beneficial bacteria to disease-causing viruses. And it is a pretty hefty population: it is estimated that 40 trillion bacterial cells are present in and on the human body.

Grice, E. A. & Segre, J. A. Nature Rev. Microbiol. 9, 244–253 (2011).

A lot of work has been done looking for possible connections between MS and the gut microbiome, but the most compelling arguments have just been made with the simultaneous publication of two PNAS papers. (PNAS is the journal of the National Academy of Sciences, which has been promoting science since President Lincoln signed it into being in 1863.)

Paper #1: This research group analyzed the stool microbiomes of 71 people with MS not taking MS-modifying drugs and 71 healthy people. They compared the microorganisms in people with MS with those in healthy people and identified several microorganisms that were either higher or lower in people with MS. To explore whether these particular microorganisms have immunological effects, they took blood cells from healthy people and dosed them with extracts of killed bacteria. Then they looked to see how T cells were affected. (T cells are immune cells in the blood that are important to the development of MS.) They found that T cells proliferated (increased their numbers) and differentiated (took on more specialized roles) differently when exposed to the extracts of certain bacteria. The bacteria that was higher in people with MS seemed to induce T cells to more inflammatory characteristics, while bacteria that was lower in people with  MS promoted anti-inflammatory T cell characteristics. And here’s the kicker: they took mice lacking any other bacteria (germ-free mice) and dosed them with the different bacteria. They found the same results in mice as they did with the blood cells: the bacteria that are higher in MS patients induced a pro-inflammatory response. Further, when the EAE mouse model of MS was induced in mice with the bacteria that was higher in people with MS, the mice had worsened disease scores as compared to controls!

Paper #2: In this work, they looked at 34 pairs of identical twins where one has MS and the other does not. (Twin studies are super helpful for complex diseases such as MS, as they help limit the influence of genetic differences and emphasize environmental factors.) They compared stool microbiomes between the twins, and noted an increase in some types of bacteria in the twins with MS. They next dosed germ-free mice with fecal samples from either the twin with MS or the twin without MS. The mice that got the fecal sample from the twins with MS experienced spontaneous EAE (mouse model of MS) at higher frequency than mice who got fecal samples from twins without MS. The mice also appeared to have changes to certain metabolic pathways depending on whether they received MS or non-MS human stool, as measured by metabolite levels in the stools of the mice. The mice who received stool from the twins with MS also had an increased inflammatory response.

While both studies identified bacteria at different levels in the people with MS as compared to healthy controls, they overlapped on only one type: Akkermansia was associated with untreated MS in both studies. (Akkermansia was first identified as its own bacterial genus in 2004, and has since been found in animals from Burmese pythons to chickens. Jump down to “The case of Akkermansia” in this review for more about it.) Why not more agreement? Both studies looked at relatively low numbers of people. Also, they studied people from different geographical locations and cultures (the United States and Germany, respectively), which is likely to affect microbiome content.

Akkermansia has been detected in the animals in red. Belzer C, de Vos WM. ISME J. 2012 Aug;6(8):1449-58. doi: 10.1038/ismej.2012.6. Epub 2012 Mar 22.

The most exciting thing about these studies is they suggest that the make-up of a person’s microbiome might directly change a person’s susceptibility to MS or the course of their disease. And the more we know about how MS begins and progresses, the better chance we have at learning how to slow it down and prevent it.