Published in the journal Science, the study reveals how infection with intestinal parasites altered the gut microbiome – the population of microbes that reside in the intestine – to stave off inflammatory bowel disease (IBD) in mice and humans.
Co-senior investigator P’ng Loke, PhD, of New York University (NYU) Langone Medical Center, and colleagues say their results support the “hygiene hypothesis,” which suggests that early exposure to infectious microbes can help protect against disease by strengthening the immune system.
Poor hygiene and sanitation are key risk factors for intestinal parasites, and such risk factors are common in developing countries, where infection with intestinal parasites is most prevalent.
However, it is developed countries that have the highest rates of IBD. According to the Centers for Disease Control and Prevention (CDC), around 1-1.3 million people in the US have IBD, including Crohn’s disease and ulcerative colitis.
In IBD, the immune system mistakes material in the gut – such as food and certain bacteria – for foreign bodies and attacks the intestinal cells, causing chronic inflammation.
Could lack of exposure to such parasites in “too-clean” developed countries be a cause of IBD?
Intestinal worms led to 1,000-fold reduction in IBD-related gut bacteria
To find out, Loke and colleagues infected mice with intestinal parasites by feeding them 10-15 whipworm eggs. The mice lacked a gene called NOD2, which is associated with IBD and a number of other immune disorders.
On comparing the gut bacteria composition of the mice with non-infected rodents, the researchers found that those infected with whipworm experienced up to a 1,000-fold reduction in Bacteroides – a bacterial species that has been previously linked to increased risk for IBD.
The infected mice also experienced a 10-fold increase in the number of Clostridia – a bacterial species that has been linked to reduced inflammation.
What is more, the researchers found that the infected mice also experienced a near-complete eradication of many symptoms of IBD, including ulceration and intestinal bleeding, compared with the non-infected mice.
The team suggests that the immune response to parasitic worms is responsible for the increase in Clostridia. These bacteria then either outmatch Bacteroides when it comes to nutrient intake, or release substances that are toxic to Bacteroides, they hypothesize.
Findings ‘link parasites, bacteria to origin of IBD’
The researchers also analyzed stool samples collected from 75 individuals residing in rural areas of Malaysia, where rates of IBD are low but incidence of intestinal parasite infection is high.
On comparing the stool samples with those of 20 individuals from a nearby urban area of Malaysia, the team found that those from rural areas had significantly fewer Bacteroides but more Clostridia in their microbiomes than those from the urban area.
Furthermore, the researchers found that individuals treated for intestinal parasite infection with deworming medication had lower levels of Clostridia and higher levels of Bacteroides.
Loke says their finding are “among the first to link parasites and bacteria to the origin of IBD, supporting the hygiene hypothesis.”
Co-senior researcher Ken Cadwell, PhD, also of NYU Langone Medical Center, adds:
“Our study could change how scientists and physicians think about treating IBD. Patient testimonials and anecdotes lead many to think that worms directly cure IBD, while in reality, they act on the gut bacteria thought to cause the disease.”
The findings build on those of another study from the team in 2012, which found that monkeys with the simian form of IBD could be treated with worm eggs. They found the eggs were able to trick the immune system into thinking the monkeys had an intestinal parasite infection, which induced a response that lowered gut inflammation.
In future research, the team plans to determine exactly how Clostridia outmatch Bacteroides, as well as hunt for harmlessClostridia species that can do the same job.
Additionally, they want to investigate whether worm infection can help fight any other autoimmune diseases – such asmultiple sclerosis (MS), rheumatoid arthritis or type 1 diabetes – by altering the gut microbiome.