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  • When gut microbes break down prebiotic dietary fiber, several molecules that can modulate the immune system can form.
  • However, scientists still do not understand the inflammatory effects that may arise when the body metabolizes specific dietary fiber types.
  • A recent study in mice showed that an inulin supplement changed the metabolism of certain gut bacteria, resulting in an increase in the serum levels of bile acids.
  • The researchers observed that inulin triggered a specific type of inflammatory response, typically observed in response to allergies and parasitic worms, in the lungs and colon.

A recent study published in Nature suggests that the dietary fiber inulin can alter the composition and metabolism of gut microbiota, resulting in a type-2 inflammatory response, which is typically observed in response to allergic respiratory conditions.

The study calls into question the relationship between diet, immunity, and usually beneficial prebiotics—in this case, inulin, a dietary fiber commonly used in anti-inflammatory supplements.

Commenting on the study’s findings, Dr. Sarkis Mazmanian, a microbiologist at the California Institute of Technology, said:

“The results are counterintuitive based on previous literature showing anti-inflammatory properties of dietary fiber, though how microbiota-derived metabolites shape type 2 immunity is likely complex and still poorly understood.”

Dr. Mazmanian said that the study offers new insights into how dietary fiber, gut bacteria, and the immune system interact.

“Extrapolation to humans, either in terms of biological relevance or possible interventions, remains limited. However, the study does raise intriguing new insights that will require replication and further research toward mechanisms of action,” he told Medical News Today.

The gut microbiota plays an important role in human health and disease. The gut microbiota can modify dietary components and molecules the body produces, such as bile acids, to produce a vast array of biologically active compounds. These metabolites, the intermediate or end products of bacterial metabolism, can influence the host’s metabolism and immunity.

Diet can influence the composition of the gut microbiome, which, in turn, can influence the production of these metabolites.

For instance, certain types of dietary fiber can act as prebiotics— foods that can influence the growth and activity of the gut microbiota to produce beneficial health effects. These prebiotic dietary fibers cannot be digested by human enzymes in the small intestine and are broken down by fermentation by gut microbes in the large intestine.

The fermentation of undigested dietary fiber by the gut bacteria produces metabolites such as short-chain fatty acids, including acetic acid, butyric acid, and propionic acid. Previous studies have shown that these short-chain fatty acids can have a beneficial impact on metabolism and produce anti-inflammatory effects.

However, in addition to short-chain fatty acids, the breakdown of dietary fiber by gut microbiota also produces other metabolites, including branched-chain amino acids, indoles, and bile acids.

There are multiple different types of dietary fiber, including inulin, cellulose, and lignin, with each dietary fiber type differentially impacting gut microbiota composition and the production of microbiota-derived metabolites.

Although researchers have extensively examined the effects of short-chain fatty acids on the metabolic and immune systems, the effects of consuming a diet rich in a specific type of dietary fiber on the immune system are not well understood.

In the present study, the researchers examined the impact of a diet enriched in inulin, a type of soluble dietary fiber, on gut microbiota composition and inflammation.

Inulin is a storage carbohydrate in several plants and is composed of repeating units of fructose. For instance, inulin is present in bananas, onions, artichokes, garlic, wheat, oats, garlic, and chicory.

Inulin is not digested in the small intestine and is a prebiotic fiber. Animal studies suggest that inulin can stimulate the production of short-chain fatty acids and improve lipid and glucose metabolism.

Moreover, there is evidence to suggest that dietary supplementation with inulin can promote weight loss in humans. As a result, inulin is used as a dietary supplement and as a bulking agent in processed foods.

Previous studies had shown that inulin can increase the levels of regulatory T cells that can suppress the response of the immune system. In the present study, the researchers further examined the impact of inulin on the immune system in mice.

To examine the impact of inulin on gut microbiota, the researchers used mice that were maintained on either an inulin-rich diet or a calorie-matched control diet for two weeks.

The inulin-rich diet led to an increase in bacteria belonging to the Bacteroidetes phylum and a decline in those from the Firmicutes phylum.

The inulin-rich diet also engendered changes in the levels of several microbiota-derived metabolites in the serum. The largest change in mice maintained on the inulin-rich diet was observed in the serum levels of bile acids.

Bile acids, the major constituents of bile, are produced by the liver and can facilitate the digestion and absorption of fats in the small intestine.

“[The study reveals that] a modified fiber diet modulates type 2 immunity via effects on bile acids, defining a new diet-microbiome axis that impacts inflammation in the gut and lungs of mice.”
— Dr. Sarkis Mazmanian

After their synthesis from cholesterol, bile acids are conjugated with the amino acids glycine and taurine in the liver. Upon traveling to the intestine, bile acids can be transformed by enzymes produced by gut bacteria. For instance, the bile salt hydrolase enzyme secreted by gut microbiota deconjugates bile acids from glycine and taurine in the small intestine.

In the present study, the researchers found an increase in the levels of major types of unconjugated bile acids, such as cholic acid, in the serum.

Previous studies have shown that bile acids can modulate the immune response. Hence, the researchers examined the effects of inulin on the immune response.

Consistent with previous studies, inulin produced a modest increase in regulatory T-cell levels. Furthermore, mice maintained on an inulin-rich diet showed an increase in the level of eosinophils, a type of white blood cells, in the colon and lungs.

Such elevated eosinophil levels are a characteristic of a specific type of immune response called type-2 inflammation, which is typically observed in allergies, asthma, and eczema.

In addition, inulin also caused an upregulation of immune cells and inflammatory proteins involved in mediating a type-2 inflammatory response.

The researchers then examined the role of gut microbiota in mediating the inulin-induced type-2 inflammatory response. They found that germ-free mice—i.e., mice lacking microbiota— maintained on an inulin-rich diet did not show an increase in eosinophil levels in the colon.

Moreover, germ-free mice inoculated with a single bacterial strain and fed an inulin-rich diet showed elevated serum cholic acid levels and promoted a type 2 inflammatory response. This inulin-induced type-2 inflammatory response was abolished in germ-free mice inoculated with the same bacterial strain lacking a functional bile salt hydrolase enzyme.

In addition, oral administration of cholic acid, but not short-chain fatty acids, for 2 weeks also triggered the type-2 inflammatory response similar to that observed with inulin.

These data show that gut microbiota is necessary for mediating the effects of inulin on type-2 inflammation.

Moreover, the necessity for a functional bacterial bile salt hydrolase enzyme to trigger the type 2 inflammatory response suggests an essential role for microbial metabolism of bile acids in mediating the inulin-induced type-2 inflammation.

The inulin-rich diet also caused changes in microbiota composition, an increase in serum bile levels, and activation of the type-2 inflammatory response in the germ-free mice transplanted with human microbiota.

These effects were similar to those observed in mice with a diverse microbiota maintained on the inulin-rich diet. This shows that inulin had a similar impact on both human and mouse microbiota.

The researchers found that inulin consumption led to a more severe type-2 inflammatory response in mice responding to allergens, such as house dust mites and the food additive papain.

For instance, exposure to house dust mites resulted in a heightened type-2 inflammatory response in the lungs and increased airway resistance, indicative of a decline in lung function.

In contrast to these adverse effects, the elevated type-2 inflammatory response due to inulin had a protective effect against parasitic worms, resulting in their more rapid removal.

Thus, although inulin could potentially exacerbate allergic reactions in susceptible individuals, an inulin-rich diet may not necessarily have a negative impact on healthy individuals.

The study’s author Dr. Mohammad Arifuzzaman, a postdoctoral researcher at Weill Cornell Medical College, noted, “It could be that this inulin to type-2-inflammation pathway represents an adaptive, beneficial response to endemic helminth parasite infection, though its effects in a more industrialized, helminth-free environment are more complex and harder to predict.”

Molly Rapozo, registered dietician, nutritionist and brain health coach at Pacific Neuroscience Institute at Providence Saint John’s Health Center in Santa Monica, CA, said dietary fibers can be beneficial in multiple ways, and “therefore the positive effects could certainly supersede any negatives.”

However, she cautioned that more research was needed, especially in humans.

“The inflammatory effect of inulin in this study doesn’t necessarily outweigh the benefits of dietary fiber overall, however, this is an opportunity to look at our sources of inulin fiber,” she said.

She also advised choosing whole food sources of prebiotic fibers like inulin, instead of choosing highly processed foods and supplements.

Getting inulin from food

“Choose more whole food sources of inulin such as Jerusalem artichokes, onions and leeks, garlic, chicory root (in coffee and coffee substitutes), dandelion greens, jicama, asparagus, flaxseed, oats, wheat, and barley.”
— Molly Rapozo, registered dietician