Microbiota, Metabolome and Nutrition: an 'Artificially Intelligent' Way to Personalized Nutrition

Irritable bowel syndrome (IBS) is a chronic intestinal condition whose high incidence and prevalence make it a major healthcare problem(3-7). IBS affects 7-15% of the general population(6, 7). It is twice as frequent in women(8) and is diagnosed more often in patients less than 50 years of age(9). It is characterized by recurrent episodes of functional gastrointestinal symptoms whose pathophysiological mechanisms are not completely clear(10). The most common symptoms include abdominal pain, bloating, constipation, and/or diarrhea(10). IBS negatively impacts quality of life and causes a substantial burden on healthcare resources(11, 12). Like the clinical phenotypes, the pathophysiological mechanisms underlying the syndrome are heterogeneous and not fully understood(13). However, there is evidence that IBS may result from a combination of gastrointestinal motility changes, visceral hypersensitivity, low-grade inflammation, altered microbiota, and food components(14-17). Due to the diversity of IBS symptoms and their considerable variability over time, a wide range of pharmacological treatments are employed which often only target the primary symptom; thus, when multiple symptoms are present, the treatments administered are often inadequate. This has led to the investigation of use of dietary therapies as a treatment option.

Dietary restriction of fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) have been recently investigated in the management of functional gut symptoms in IBS. An increasing number of uncontrolled and controlled trials have examined the clinical effectiveness of a low FODMAP diet in patients with IBS using either dietary advice or feeding protocols. Uncontrolled and unblinded controlled trials suggest symptom response rates in patients with IBS are as high as 85%(18). Similarly, a beneficial impact on symptoms has been reported in blinded randomized controlled trials(19-22). A potential shortcoming of the low FODMAP diet and of any diet that involves multiple food exclusion, is the risk of nutritional inadequacy, and this is especially pertinent if the excluded foods are nutrient-rich. The low FODMAP diet requires substitution of selected food items across a number of food groups and, therefore, there is the potential for inadequate intake of nutrients, particularly carbohydrate, fiber, iron, B vitamins, and calcium. Another potential safety concern associated with implementation of the diet relates to the impact on the gastrointestinal microbiota, which has been implicated in the pathogenesis of IBS(23) and has been associated with clinical features of IBS including abdominal pain, anxiety, and depression(24, 25). Hence, we propose to evaluate the microbiome and metabolome in IBS patients to create datasets of integrated data through AI tools. Furthermore, we aim to determine the effects of a low FOODMAP diet based on fermented products on the microbiome and metabolome in IBS patients. These evaluations will allow to assess patient's nutrient deficiency and the general quality of life pre and post intervention among groups and to develop a personalized treatment that will increase the quality of life in IBS patients.

The low FODMAPs diet is associated with limitations particularly due to the elimination of several food items which can cause worsening of the side effects due to significant alteration of the intestinal microbiota composition and an overall reduction of the nutritional status. Although, probiotics seem to have beneficial effects on improving this side effect, their way of function is still relatively unknown. Much remains to be answered as to which strains is/are most effective across the broad spectrum of IBS patients and whether single or combination of strains work best. This leads to the question of whether individual differences among IBS patients in terms of microbiome diversity could affect the efficacy of probiotics therapy. Therefore, with our approach we propose a reshaping of the host-microbiota interactions through personalized nutrition which could be a new therapeutic avenue for both disease control and prevention. Specifically, we believe that a diet supplemented with previously fermented food items will be beneficial for the patient's condition. This fermentation will be controlled and performed with Lactobacillus paracasei strain CNCM I-5220. Through the longitudinal study we will be able to evaluate their grade of the disorder at baseline (one week of low FODMAP diet), and the effect of the fermented food items on their microbiota and metabolome after one and two weeks. Furthermore, by adopting new efficacious treatment options, it might be possible to decrease the high recurrence rate of IBS patients to the public health system, improving patient's quality of life and decreasing the costs for the National Sanitary System (SSN).

The primary objective will be to assess the enterotypes of IBS patient at baseline and to analyze how supplementation of fermented food modifies the microbiome and metabolome in IBS patients following a low FODMAP diet.

As secondary objective, we will compare the efficacy and safety of two different nutritional approaches on IBS symptoms.