Humira, Smoking Can Alter Gut Microbiome in AS, Study Finds

Both treatment with Humira (adalimumab) and smoking can alter the composition of the gut microbiome — the microorganisms living in the gut — in people with ankylosing spondylitis (AS), a new study shows.

Results also revealed that nonsmokers showed greater reductions in disease activity than smokers upon starting Humira.

The study, “Dynamic changes in gut microbiota under the influence of smoking and TNF-α-blocker in patients with ankylosing spondylitis,” was published in the journal Clinical Rheumatology.

The human gut is home to billions of microbes. These intestinal dwellers impact human health and disease in a variety of ways, many of which are only beginning to be understood. In particular, the gut microbiome is known to influence inflammation, and abnormalities have been linked to AS. Yet, how the gut microbiome responds to AS treatments, and the consequences of these changes, are open areas of investigation.

TNF-alpha inhibitors, such as AbbVie‘s Humira, are a class of anti-inflammatory medications. These therapies work by blocking the activity of TNF-alpha (tumor necrosis factor alpha), a powerful pro-inflammatory signaling molecule.

In the study, researchers in China examined how the gut microbiome changed in response to Humira treatment in 20 people with AS.

They analyzed the bacterial content of fecal samples before treatment, as well as after one, three, and six months of therapy. For comparison, 20 samples were collected from people without AS, at a single point in time.

Because smoking can alter the compositon of the gut microbiome, lessen response to TNF-alpha inhibitors, and increase AS severity, smokers and nonsmokers were analyzed separately. The study included 10 smokers in the AS group and nine in the controls.

Results showed significant variability in the participants’ gut microbiome. Within the AS group, g_Comamonas and g_Desulfovibrio bacteria were more common in nonsmokers than in smokers. Also, smokers (patients and controls) shared g_Ruminiclostridium_9 and g_Ruminococcaceae UCG-003 as common bacterial genera.

Short-term changes in the abundance of many bacteria were found following the start of Humira treatment. Despite continuous increases found mainly in nonsmokers and continuous decreases primarily in smokers, “the relative abundance of most of the bacteria returned to baseline as of 6 months after the fluctuations began,” the researchers wrote.

Prior to treatment, the gut microbiome of smokers was significantly less diverse than in nonsmokers, in both AS patients and controls. However, this difference was no longer significant after Humira treatment in the AS group.

“These results indicated that anti-TNF-[alpha] treatment can improve the microbial diversity [in people with AS who smoke],” the researchers wrote.

They also evaluated changes in disease severity following Humira treatment using the Ankylosing Spondylitis Disease Activity Score (ASDAS). In keeping with previous research, nonsmokers with AS had better responses (disease activity reductions) than smokers.

The scientists then looked for associations between changes in gut bacteria and ASDAS. They found several types of bacteria whose abundance was significantly associated with differences in disease severity. Notably, many of these bacteria belong to a lineage (phyla) called Firmicutes.

“Many genera in p_Firmicutes exert anti-inflammatory effects,” the researchers wrote. This supports the idea that regulation of inflammation by the gut microbiome is important in AS disease processes.

According to the investigators, the limited number of participants and not analyzing other treatments were among the study’s limitations.

Overall, “both smoking and TNF-[alpha]-blocker had significant effects on the composition, relative abundance, and diversity of gut microbiota in AS patients,” they wrote.