Apigenin remodels the gut microbiota to ameliorate ulcerative colitis

The study by Fu et al., titled Apigenin Remodels the Gut Microbiota to Ameliorate Ulcerative Colitis, focuses on the potential of apigenin, a natural flavonoid found in plants like celery, to treat ulcerative colitis (UC). UC is a chronic inflammatory bowel disease that causes significant discomfort, including symptoms like abdominal pain, diarrhea, and bleeding. The research highlights the importance of gut microbiota in the progression of UC, as imbalances in the gut's microbial environment can exacerbate the disease. Apigenin has been known for its anti-inflammatory properties, but this study aimed to explore its specific impact on the gut microbiome and intestinal barrier function. By improving both inflammation and gut health, the findings suggest apigenin could offer a safer, natural alternative for UC treatment.

In this study, the researchers created a UC mouse model using dextran sodium sulfate (DSS), which is known to trigger symptoms of UC. The mice were divided into five groups:

1. Control Group: Mice that were healthy and drank regular water.
2. Model Group: Mice treated with DSS to induce UC.
3. Positive Medicine Group: Mice treated with sulfasalazine (SASP), a drug commonly used to treat UC.
4. Low-Dose Apigenin Group (AP-L): Mice treated with a lower dose of apigenin (150 mg/kg).
5. High-Dose Apigenin Group (AP-H): Mice treated with a higher dose of apigenin (250 mg/kg).

The mice were monitored for 21 days, and various tests were performed to measure UC symptoms. These included measuring the Disease Activity Index (DAI), which looks at weight loss, stool consistency, and the presence of blood in the stool. Additionally, researchers evaluated the colon's physical condition, levels of inflammatory markers, and the balance of gut bacteria using 16S rRNA gene sequencing. Short-chain fatty acids (SCFAs), which are essential for gut health, were also measured.

The study used techniques like Hematoxylin and Eosin (H&E) staining to analyze tissue damage and Enzyme-Linked Immunosorbent Assay (ELISA) to detect specific inflammatory markers in the colon. This allowed researchers to see apigenin's physical and biological effects on the colon’s health.

The results from this study demonstrated that apigenin significantly improved symptoms in the mice with DSS-induced UC. Here’s a breakdown of the major findings:

Mice treated with DSS typically experience weight loss and suffer from damaged colons due to inflammation. However, in this study, mice that received apigenin showed improved weight maintenance and healthier colons with less damage. The researchers observed that apigenin "ameliorated hyperemia, swelling, surface ulcers, and splenomegaly," meaning it helped reduce swelling and injury in the colon, thus improving overall gut health.

Ulcerative colitis causes a rise in pro-inflammatory cytokines, such as TNF-α, IL-6, and IL-1β, which play a major role in increasing inflammation in the colon. Mice treated with apigenin showed a significant decrease in these harmful cytokines. At the same time, apigenin boosted anti-inflammatory cytokines like IL-10, which help control inflammation. As the researchers noted, apigenin "increased the level of IL-10 in DSS-induced colitis mice," promoting a more balanced immune response and reducing overall inflammation.

The intestinal barrier is essential for protecting the body from harmful bacteria and toxins. This barrier is often weakened in patients with UC, allowing toxins and harmful microbes to enter the bloodstream. Apigenin helped restore the gut barrier by increasing the levels of important proteins like ZO-1, claudin-1, and occludin, which are necessary for maintaining tight junctions between cells in the intestinal lining. By strengthening this barrier, apigenin protected the gut from further damage.

Gut bacteria play a crucial role in UC, and apigenin positively impacted the gut microbiota of the treated mice. The study found that apigenin increased beneficial bacteria such as  Akkermansia and  Faecalibaculum, which are known to support gut health while decreasing harmful bacteria like Klebsiella and Bacteroides. This rebalancing of the gut microbiome was crucial for reducing UC symptoms, as the gut bacteria influence inflammation and the integrity of the gut lining.

Short-chain fatty acids (SCFAs) like butyrate, acetate, and propionate are beneficial compounds gut bacteria produced during digestion. These SCFAs play an important role in reducing inflammation and maintaining gut health. The study showed that apigenin significantly increased SCFA production in treated mice. By boosting SCFA levels, apigenin helped maintain the gut barrier’s integrity and reduced inflammatory responses, which acted as a buffer against UC symptoms.

This study highlights apigenin as a promising treatment option for ulcerative colitis. Unlike traditional UC drugs, which often have side effects like immune suppression, apigenin is a natural compound with fewer known risks. The study suggests several reasons why apigenin could become an effective UC treatment:

Since apigenin is a natural compound found in everyday foods like parsley and celery, it is considered safe for regular consumption. The researchers highlighted its potential by stating that apigenin “might serve as a potential therapeutic strategy for the treatment of UC via regulating the interaction and mechanism between host and microorganism.” Its natural origin makes it an attractive option for those looking to avoid the side effects often associated with traditional medications.

Apigenin provides multiple health benefits by reducing inflammation, restoring the gut barrier, and balancing the gut microbiome. This dual-action approach means it targets several factors that contribute to UC symptoms. By addressing both inflammation and gut lining health, apigenin offers a more comprehensive treatment strategy than medications that focus on just one aspect of UC.

Due to its low toxicity and natural origin, apigenin could be taken as a daily supplement, potentially preventing and treating UC flare-ups. Its safety profile makes it suitable for long-term use, unlike some traditional UC treatments that can only be taken for short periods due to harmful side effects. Apigenin’s ability to improve gut health without significant risks positions it as a promising option for managing UC daily.

The scientific paper concludes by emphasizing the potential of apigenin as a therapeutic option for UC patients, particularly because it “ameliorates UC via balancing gut microbiota to inhibit inflammation and protect the gut barrier.”

The findings of this study reveal apigenin as a natural solution for treating ulcerative colitis by addressing both inflammation and gut microbiota imbalance. By increasing beneficial bacteria, promoting gut barrier integrity, and enhancing the production of short-chain fatty acids, apigenin could become a breakthrough treatment for UC. Its ability to reduce inflammation while boosting the gut’s natural defenses makes it an exciting option for people looking for alternatives to traditional UC medications. With further research, apigenin could treat and help prevent UC, offering a safer and more holistic approach to managing gut health.