## 1 Introduction  
Functional gastrointestinal diseases (FGIDs) are the most common cause of gastrointestinal disturbance in global population. Once organic (i.e., inflammatory or neoplastic) causes are ruled out, symptoms include a wide range of disorders [1] affecting the esophagus or upper gastrointestinal tract (i.e., functional dyspepsia, postprandial distress syndrome, or epigastric pain), bowel disorders (i.e., irritable bowel syndrome (IBS), constipation, diarrhea, or bloating), biliary and anorectal disorders, or dyspppsia. Several factors are involved in the genesis of FGIDs, and include intestinal dysbiosis [2; 3], genetic predisposition, perception, diets, and intestinal dysmotility [4]. The exact physiopathology of FGIDs, however, remains poorly elucidated so far. FGIDs can also coexist with types of food intolerance. Lactose intolerance (LI) (due to lactase deficiency, down-regulation of lactase activity, lactose malabsorption causing abdominal symptoms upon lactose-containing products) [5; 6; 7] and fructose intolerance (due to fructose malabsorption with symptoms upon ingestion of fructose-containing foods) in adults [8] can easily mimic several FGIDs. Self-reported perception of LI can also affect the behaviour of patients in terms of diagnosis and therapeutic approaches [9; 10; 11]. However, even with a lactose- or fructose-restricted diet regimen, functional symptoms like constipation or diarrhoea, functional bloating, or dyspppsia may persist.  
Recently, the idea of improving gut microbiota composition with some selected probiotic strains represents a valid therapeutical approach in FGIDs, even with concomitant LI [12]. Probiotics are defined as live bacteria or yeasts that positively supplement the gut microbiota [13]. Probiotic supplementation is a valid approach to maintain the balance of the intestinal microbiota, the composition of which could be altered by several factors (stress, lifestyle, diet, antibiotic therapies, and so on) [14]. Hence, probiotics can be administered for treatment of FGIDs, as well as carbohydrates malasorbition [15].  
In particular, lactic acid bacteria (LAB) constitute a large part of intestinal microbiota and their probiotictical properties are well documented [16]. The genus _Lactobacillus_ is a source of interest in the prevention of some diseases including LI [17]. Moreover, the beneficial use of LAB and probiotics in general aids in the extraction of energy and nutrients, such as short-chain fatty acids (SCFAs) (acetate, propionate, butyrate) and amino acids from food [18]. Furthermore, the production of SCFAs stimulates ileal propulsive contractions, releases neuroendocrine factors, acidificates the intracolonic pH, and relaxes intestinal gut tissues [19].  
In addition, there is evidence that low intake of vitamin B6 might be associated with FGIDs such as IBS [20]. Notably, B6 is shown to have pleiotropic functions for human health [21].  
The present study aimed to investigate the effects of a novel formulation of _Bifidobacterium longum_ BB536 and _Lactobacillus rhamnosus_ HN001 with vitamin B6 on symptoms, gut microbiota, and metabolome in a cohort of patients with persisting FGIDs on a lactose-free diet because of a prior diagnosis of LI.