Volume 1
Pablo Roman, ... Diana Cardona, in Comprehensive Gut Microbiota, 2022
1.29.3.3 Gut-Microbiota and Toxic Dietary Components
Lectins and phytohemagglutinins (PHA) are natural toxicants present in many foods, especially in beans and other dietary pulses, which can have toxic effects when consumed without adequate cooking, occasionally leading to an acute gastroenteritis (Kumar et al., 2013). Toxic GIT effects may be secondary to increased gut bacteria and intestinal permeability. Indeed, rats exposed to crude red kidney beans (Phaseoulus vulgaris) for 24 h showed weight loss and increased intestinal permeability, as well as increased bacterial load and increased bacterial translocation to the liver (Ramadass et al., 2010). Lectins seem to increase the levels of facultative aerobes, without an increase in obligate anaerobes (Rhodes et al., 2003). Furthermore, in vitro and ex vivo studies led to the conclusion that some lectins (at least concanavalin A) may act by promoting bacterial adherence to the small intestine, thereby facilitating colonization and infection and leading to bacterial overgrowth (Abud et al., 1989). Early in vivo studies showed that, after exposure to PHA derived from red kidney beans, the predominant bacteria proliferating in the jejunum were E. coli, Streptococcus spp. and Lactobacillus. Also, E. coli and Streptococcus spp. populations increased within 24 h of PHA exposure and remained high during further exposure to PHA but declined on reversion to a control diet within 24–48 h, with a shift to gram-positive rod and coccus flora through days 1–4 of the reversion (Banwell et al., 1988). Anyhow, adequate cooking (at 100 °C for at least 30 min) avoids the presence of toxic lectins in legumes, which may otherwise produce beneficial effects for the colonic microenvironment (including the microbiota, mucus and epithelial barriers), particularly associated with their contents in fermentable fibers, which are the source of gut-health promoting bioactive microbial metabolites, including SCFAs (acetic acid, propionic acid and butyric acid). In these regards, mice fed with diets supplemented with 20% cooked navy bean or black bean flours increased the abundance of carbohydrate fermenting bacteria, SCFAs and their receptors (Monk et al., 2017). However, a recent opinion review (Panacer and Whorwell, 2019) called for a deeper study of the impact of dietary lectins. FODMAP stands for “fermentable oligosaccharides, disaccharides, monosaccharides, and polyols”; these carbohydrates are poorly absorbed in the gut and are, therefore, fermented by colonic bacteria, leading to gastrointestinal symptoms, especially in patients with IBS. Although the use of a diet low in FODMAPs can dramatically improve the symptoms of many patients, gut microbiota may become affected by such restrictive diet (Staudacher and Whelan, 2017). The authors highlighted that many of the foods excluded in the low FODMAP diet also contain lectins, suggesting that restrictions of more specific dietary components (i.e., lectins) might be more broadly beneficial for IBS patients (Panacer and Whorwell, 2019). Since dysbiosis occurs in IBS patients (Carco et al., 2020), more research is needed to clarify the role of lectins on this (Spiller, 2021).
Dietary AGEs are not fully digested and absorbed in the GI tract, thus reaching the colon, where they may undergo fermentation by the resident microbiota. Colonic protein fermentation leads to the formation of ammonia, amines, phenols and sulfides (Tuohy et al., 2006; Gilbert et al., 2018), that negatively affect the colon. As a consequence, the composition of the microbiota and its production of SCFAs, which are generally considered anti-inflammatory, can change (Vinolo et al., 2011; Li et al., 2018). In animal models, diets high in dietary AGEs were associated with a decrease in Bacteroidetes, Bifidobacteria, Lactobacilli, and alpha-diversity, suggesting a less healthy condition of the GIT (Snelson and Coughlan, 2019). In vitro studies confirmed that the effects of dietary AGEs on gut microbiota are largely dependent on food composition and thermal treatment (Pérez-Burillo et al., 2018). Furthermore, dietary AGEs may contribute to some of the symptoms and possibly the disease course of IBD through microbiota modulation, suggesting that decreasing the levels of foods rich in these compounds may be helpful in IBD patients (van der Lugt et al., 2020).
Acrylamide and its metabolites have been recognized as potential carcinogens or co-carcinogens (including in the colon, see (Raju et al., 2013; Hogervorst et al., 2014; El Asri et al., 2020): and neurotoxic agents (including to the enteric nervous system, see (Lourenssen et al., 2009). However, the direct impact of acrylamide on gut microorganisms is not clear. Different deleterious effects were demonstrated to occur in Bacillus subtilis (Tsuda et al., 1993), E. coli (Starostina et al., 1983) and Saccharomyces cerevisiae (Kwolek-Mirek et al., 2011) cultures, whereas Salmonella typhymurium was not affected (Shipp et al., 2006). As mentioned earlier, fructose-asparagine (F-Asn) is a precursor to acrylamide that is found in human foods, and a nutrient source for Salmonella enterica, a foodborne pathogen, whose serovars Typhimurium and Enteriditis cause inflammatory diarrhea in humans. Interestingly, it was found that some species present in the normal intestinal microbiota, particularly three members of the Clostridium genus, are able to use F-Asn, suggesting that these clostridial species may contribute to competitive exclusion of Salmonella (Sabag-Daigle et al., 2018). Furthermore, some microorganisms present in the colon or delivered with food may be able to degrade acrylamide by amidase production, including Bacillus clausii (Lippolis et al., 2013), Enterococcus faecalis (Mesnage et al., 2008) and Helicobacter pylori (Bury-Moné et al., 2003). Some lactic acid bacteria were shown to remove acrylamide in aqueous solution by simply physically binding the toxin to the bacterial cell wall (Rivas-Jimenez et al., 2016), suggesting a beneficial effect of probiotics to reduce acrylamide absorption. Interestingly, Petka et al. (2020) found that several Lactobacillus species were tolerant to acrylamide even at high concentrations (up to 1 g/mL) in culture. Besides, some of them, like L. plantarum, L. lactis sp. Lactis, and L. brevis, as well as the probiotic strain Lactobacillus acidophilus LA-5 showed an increased growth rate in the presence of high concentrations of the toxin. These results suggest that these bacteria may use this toxin as a source of energy. However, L. plantarum cell division was uncoupled, and these bacteria appeared in the form of chains and diplobacillus. The authors concluded that acrylamide-containing products would be not as harmful as previously thought, provided a properly functioning intestinal microbiota is present (Petka et al., 2020).
The impact of mycotoxins on the gut microbiota has recently been thoroughly reviewed (Liew and Mohd-Redzwan, 2018; Gao et al., 2020; Guerre, 2020). The intestinal barrier is composed of the physical (enterocytes), chemical (mucin, etc), immune and microbial (gut microbiota) barriers and all of them may be affected by mycotoxins (Gao et al., 2020), favoring the development and exacerbation of chronic intestinal inflammatory diseases (IBD, celiac disease, and even IBS). Some in vivo studies reported mycotoxin-induced modifications in gut microbiota of animals by advanced molecular approaches. For example, Coprococcus genus was more abundant in rats fed with the trichothecene deoxynivalenol (DON) (Miró-Abella et al., 2018). In pigs fed with DON and zearalenone (ZEN) Lactobacillus was found to be more abundant in one report (Reddy et al., 2018), whereas increased abundance of Erysipelotrichaceae and decreased abundance of Ruminococcaceae, Streptococcaceae, and Veillonellaceae were reported in another study (Le Sciellour et al., 2020). However, Daud et al. (2020) did not find any impact of mycotoxin (unconjugated or masked forms) on the growth of any bacterial strain tested, suggesting that mycotoxins do not act directly on gut microbes (Daud et al., 2020). Thus, the toxicity exerted by mycotoxins on the large intestine and gut microbiota might be more likely attributable to secondary effects on microbiota composition associated with host-toxicity and consequent barrier impairment, which warrants further investigation. Interestingly, these authors also demonstrated that several strains of gut bacteria are likely to hydrolyze masked mycotoxins in the human gut due to their high activity and high prevalence in the gut, including Eubacterium rectale A1-86, Roseburia intestinalis L1-82, Butyrivibrio fibrisolvens 16/4 and Prevotella copri DSM 18205, as well as Bifidobacterium adolescentis and Lactiplantibacillus plantarum. Masked mycotoxins are sugar conjugates formed by the cereals and are stable toward small intestinal digestion, i.e., they are not absorbed intact (Gratz, 2017), but the parent mycotoxins may be released by the gut microbiota (Daud et al., 2020) and absorbed and excreted in the urine, as shown in humans (Vidal et al., 2018), contributing to overall mycotoxin systemic toxicity. Importantly, this process will vary depending on the individual composition of the gut microbiota. Furthermore, the use of probiotics (Bifidobacterium and Lactobacillus spp.) and prebiotics boosting the numbers of specific gut bacteria may influence the hydrolysis of masked mycotoxins (Daud et al., 2020). It is also important to realize that the co-occurrence of different mycotoxins in contaminated foods is the most likely situation and therefore, the possible synergistic, additive, and antagonistic effects of these compounds need to be also taken into account, but has only been scarcely addressed so far, through complex combinatorial approaches (Gao et al., 2020).