Mediterranean diet produces changes in the gut microbiome associated with clinical remission in patients with ulcerative colitis

May 23, 2023 | Nutrition

Nutritional patterns are important in treatment of ulcerative colitis because of their influence on the symbiosis between gut microbiome, host and inflammation. The Canadian authors examined the efficacy of the Mediterranean diet compared with a Canadian habitual diet on ulcerative colitis activity, inflammation, and the gut microbiome. The results showed that the Mediterranean diet produces changes in the gut microbiome that were associated with clinical remission in patients with ulcerative colitis.

Ulcerative colitis is a chronic inflammatory bowel disease with debilitating symptoms, including bloody diarrhoea, abdominal pain, cramping, tenesmus, and fatigue. The pathogenesis of diseases such as inflammatory bowel disease is linked to alterations in the gut microbiome- dysbiosis.

The Mediterranean diet is characterized by increased consumption of legumes, whole grains, vegetables, fruits, nuts, seeds, and olive oil, the moderate consumption of fish, poultry, and dairy foods, and a low consumption of processed foods and red meat. The combination of high levels of dietary fibre, phytochemicals, and fat blend (high monounsaturated fat) confers beneficial anti-inflammatory and antioxidant properties.

About the study

The authors conducted a prospective, randomized, controlled trial in 28 adults (18–65 years , median age 47 years) who had been diagnosed with mild-moderate ulcerative colitis in remission. A total of 96% of participants who were in remission, except for one participant who had a mild illness, entered the study. The study included participants who were on a stable dose of therapy for ulcerative colitis (no dosage adjustments for 2 months before starting the study for participants prescribed oral 5-aminosalicylates, thiopurines, or methotrexate), or who were taking biologics (infliximab, adalimumab) for 3 months before starting the study.

Disease activity was assessed at baseline and week 12 through the Simple Clinical Colitis Activity Index (SCCAI) and the Partial Mayo Score. Also, faecal calprotectin, which is a useful clinical marker for predicting impending relapse and directly measures intestinal inflammation, was measured at baseline and week 12. The 16S rRNA gene amplicon sequencing was used to analyze stool samples.

Participants were randomized to a Mediterranean diet (n = 15) or a Canadian habitual diet (n = 13) for 12 weeks. The primary objective of the study was to determine whether a Mediterranean diet could reduce disease activity measured by the SCCAI score at week 12. A reduction of SCCAI >1.5 was considered clinically significant. The secondary objective was to assess the cncentrations of faecal calprotectin and the changes in the gut microbiome. The evidence indicates a lack of diversity and a general instability in ulcerative colitis, often with a dysbiosis characterised by the relative depletion of Faecalbacterium praustnitzii and Roseburia hominis and the enrichment of Escherichia coli, Ruminococcus torques, and R. gnavus.

At week 12, the Partial Mayo Score significantly increased by 46% in the group of Canadian habitual diet with mild and moderate disease versus 33% in the group of Mediterranean diet with mild disease.

The majority of participants in both groups had faecal calprotectin concentration below 100 μg/g at baseline. At week 12, the concentration of faecal calprotectin was below 100 μg/g in 87% of participants on the Mediterranean diet versus 25% of participants on the Canadian habitual diet. There was no significant difference in the concentration of faecal calprotectin between the Mediterranean diet before and after the intervention. There was, however, a significant increase in the concentration of faecal calprotectin in the participants on Canadian habitual diet before and after the intervention. These data show that the Mediterranean diet is well tolerated, reduces bowel symptoms, and has anti-inflammatory effects, compared to Canadian habitual diet.

The sIgA has been found to play an important role in mucosal immunity. The potential mechanism is the ability to bind pathogenic bacteria, ultimately influencing the microbiota composition. Results showed that the Mediterranean diet significant increased faecal sIgA from baseline to week 12. In contrast, Canadian habitual diet did not affect faecal sIgA concentrations.

The Mediterranean diet also induced changes in the microbial species associated with a protective role in colitis, as well as the production of total faecal short chain fatty acids. At baseline and week 12, the stool was analyzed by 16S ribosomal RNA sequencing. Of the top 10 taxa most positively associated with the Mediterranean diet, 9/10 taxa belonged to the phylum Firmicutes, class Clostridia, and largely Clostridium subclusters IV (Ruminococcus spp., Flavonifractor spp), subcluster XIVa (Clostridium M, Blautia A), and Lactococcus spp. One taxon belonged to the phylum Bacteroidota, genus Alistipes. The scientific literature has shown that several of these species play a protective role in rodent models of colitis. In contrast, others are linked to the degradation of compounds found in food substrates that regulate host health (Clostridium boltae, Ruminococcus bromii, Blautia A spp., and Lactococcus lactis).

Among the top-ranked taxa most negatively associated with the Mediterranean diet, most taxa belonged to the phylum Firmicutes, followed by Actinobacteriota and Bacteriodota. Bifidobacterium, An144, GCA-900066135, Veillonella, Blautia, Streptococcus, and Massiloclostridium were the dominant genera. The predicted genera negatively associated with the Mediterranean diet were opportunistic pathogens (Veillonella dispar, Veillonella obetsuensis, Prevotella copri, and Streptococcus australis). This analysis of the bacteriome shows that the Mediterranean diet is associated with reshaping the gut microbiome.

Faecal short chain fatty acids are produced by microbes and have important immunomodulatory properties. They promote gut homeostasis. The patients with an inflammatory bowel disease have lower levels of total faecal short chain fatty acids than healthy controls. They also have a reduced abundance of total faecal short chain fatty acid-producing bacteria.

The results showed higher levels of total faecal short chain fatty acids, acetic acid, and butyric acid in the Mediterranean diet group than in the Canadian habitual diet group.

The researchers concluded that a Mediterranean diet induces changes in the gut microbiome and reduces faecal calprotectin concentrations, which is associated with maintenance of clinical remission in patients with quiescent ulcerative colitis.

The authors concluded that the Mediterranean diet is a reasonable, healthy dietary pattern. The Mediterranean diet may be recommended to patients with remission of ulcerative colitis to prevent relapse, in addition to their standard medical therapy.

This article was published in the Journal of Crohn’s and Colitis.

Journal Reference

Haskey N. A Mediterranean Diet Pattern Improves Intestinal Inflammation Concomitant with Reshaping of the Bacteriome in Ulcerative Colitis: A Randomised Controlled Trial. Journal of Crohn’s and Colitis, 2023, XX, 1–10. Advance access publication, 24 April 2023 (Open Access).

It should be noted that meta-analysis of dietary programs found that Mediterranean and low fat diets reduce all cause mortality and non-fatal myocardial infarction in patients with increased cardiovascular risk. The absolute effects of both dietary programs were more pronounced for patients at high risk.