Longer studies are needed to understand if these medicines can fully restore the gut microbiome, the researchers noted, adding that stool exams may be a safer and more convenient alternative to endoscopy for monitoring treatment response in pediatric patients.
The study, “Changes in the Intestinal Microbiota Are Seen Following Treatment with Infliximab in Children with Crohn’s Disease,” was published in the Journal of Clinical Medicine.
The gut microbiome, also known as gut microbiota, refers to the diverse population of microbes (bacteria, fungi, and viruses) living in the intestine, which play important roles in both health and disease.
Numerous studies have shown that inflammatory bowel diseases (IBD) are associated with an imbalance of gut bacterial communities, a phenomenon known as gut microbial dysbiosis. In a dysbiotic gut, bacteria species normally dominant become underrepresented, while bacteria groups that are usually confined start growing.
Such imbalances may actually be among possible mechanisms contributing to the development of IBD, which includes both ulcerative colitis (UC) and Crohn’s disease (CD).
Biologics known as anti-TNF agents are currently considered the most effective medications to treat severe cases of IBD. These agents work by inhibiting inflammation and promoting tissue healing in the bowel. Infliximab (marketed as Inflectra, Remicade, and Remsima, among others) is one of these, and is widely used to treat children with Crohn’s disease.
Previous studies have shown that biologics may help reduce IBD-related microbial dysbiosis as well. However, few studies have focused on investigating this potential benefit in children with Crohn’s.
They analyzed the gut microbiota of 18 children and adolescents with severe Crohn’s, ranging in age from 2 to 18, before and after starting induction therapy with Remsima. They also analyzed the gut microbiota of 18 healthy children, who served as a control group.
Microbiota composition was determined by sequencing bacterial DNA isolated from stool samples, using a technique called next-generation sequencing.
Patients received Remsima (marketed by Celltrion Healthcare) at a dose of 5 mg/kg (induction dose) administered at the start of the trial, and after two and six weeks. Stool samples were collected before Remsima was started, and after six to eight weeks of treatment (before patients were changed to a maintenance dose).
All patients responded to induction therapy: 88% entered remission, and in 12% the disease eased from severe to mild. Patients gained weight, and their disease activity and intestinal wounds were eased, as measured by the pediatric Crohn’s disease activity index and colonoscopy, respectively.
The levels of calprotectin, a fecal marker of gut inflammation, also dropped significantly over the course of treatment, from 1,920.44 µg/g to 629.17 µg/g. A detailed analysis of changes in the gut microbiome showed clear differences in the abundance of bacterial groups between children with and without Crohn’s.
Compared with healthy children, those with Crohn’s had lower numbers of bacteria from the groups of Bacteroidales, Erysipelotrichaceae, Clostridiales (e.g., Faecalibacterium prausnitzii), Bifidobacterium, and Lactobacillus.
In contrast, patients had more bacteria belonging to the groups of Enterobacteriaceae (e.g., E. coli), Pasteurellaceae, Fusobacteriaceae, Neisseriaceae, Veillonellaceae, Gemellaceae, Ruminococcus, and Clostridium spp.
Bacterial richness and diversity was lower in patients prior to therapy, as compared with healthy children, but rose back to normal levels following treatment. This was confirmed with different microbial diversity indexes.
As expected, dysbiosis was more pronounced in patients than in controls, but tended to normalize with treatment and to lower down to levels in the healthy range.
“At present, it is difficult to determine whether dysbiosis in patients with IBD is a cause or consequence of the disease,” the researchers said. “Perhaps there is a vicious circle mechanism: inflammation is the cause of dysbiosis, and dysbiosis increases inflammation.”
“The results show that biological treatment is associated with changes in the intestinal microbiome of patients with CD,” they said. “These changes result in an intestinal microbiome pattern similar to that seen in healthy children.”
Longer follow-ups are needed to determine whether treatment can lead to a fully restored, healthy-like gut microbiome, they noted.
A stool exam may offer a more convenient and low-risk alternative to endoscopy as a complementary method to monitor response to treatments, they said.
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