The digestive tract is the most heavily colonized organ in humans with the colon alone estimated to contain more than 70 % of all human microbes [9]. The gut microbiome (microbiota, microflora, or flora) coexists with the host and influences the host’s own metabolism, nutritional status, and immune function (Fig. 4.2). Four bacterial phyla are commonly found in humans: Firmicutes (e.g., Streptococcus, Lactobacillus, Clostridia), Bacteroidetes (e.g., Prevotella, Bacteroides), Proteobacteria (e.g., Haemophilus, Escherichia, Salmonella, Oxalobacter), and Actinobacteria (e.g., Propionibacterium, Bifidobacteriales) [11]. For more than 100 years, the existence of gastrointestinal microbes and their beneficial effect on health have been known [7]. The use of kefir by people in the Bulgarian area was attributed to their notably longer life expectancy at the turn of the twentieth century than that of other Europeans [12]. Indeed, a species of lactic acid bacteria – Lactobacillus bulgaricus – owes its name to this observation. The gastrointestinal tract normally contains more than 1,000 known different species of bacteria [11], many of which are pathogenic if allowed to overgrow but many others of which are beneficial and thus known as probiotics. The definition of a probiotic has changed and continues to change over time but is most commonly and basically defined as a live microorganism that confers a health benefit to the host [13, 14] (Table 4.1).

As bacteria ferment undigested food material passing into the colon, metabolites are created, many of which are increasingly recognized as beneficial to the host [9]. There are two main types of bacterial fermentation in the gut, saccharolytic and proteolytic. Saccharolytic fermentation is carbohydrate based and gives rise to beneficial metabolites such as the short chain fatty acids propionate and acetate [19]. Short chain fatty acids are integral to the health of the colonic epithelium and have a myriad of other benefits, including anti-inflammatory properties [7, 8, 11]. Proteolytic bacterial fermentation is protein based and is a source of a number of toxic metabolites, particularly uremic toxins (e.g., indoxyl sulfate and p-cresyl sulfate) [8, 20].

Bacterial populations differ depending on location in the digestive tract. Bacteria in the mouth are dominated by Streptococcus, which exist in biofilms on the surface of teeth [9]. The stomach, despite its low pH, also has a rich microbiota under normal physiologic conditions. But the highest density of gut microorganisms appears in the lower intestinal tract and is dominated by two bacterial phyla, Bacteroidetes and Firmicutes [11]. The primary gut microbial profile is thought to be fairly stable throughout a person’s life once established, but external factors can dramatically affect it [19], including the intake of substrate for bacteria [17]. Many studies have documented the effect of antibiotics on gut bacteria and their ability to induce dysbiosis [21]. In one study, antibiotic exposure was associated with an enrichment and stabilization of resistant Bacteroides strains [22]. Other studies have documented the role of antibiotics in the overgrowth of pathogenic gut bacteria such as Clostridium difficile [23]. Aging may also affect gut microbiota. The composition of the gut microbiome in people >65 years of age is distinct from that of younger adults [24].

Diet patterns and dietary changes also seem to influence the types of bacteria in the microbiome [19]. In one study, elderly adults living independently in the community had a reduction in the diversity of their gut flora after moving to assisted living, and these differences were associated with dietary changes incurred while in assisted living [25]. Differences in gut microbiome profiles have been observed in lean vs. obese individuals . Mouse studies have shown that obesity is associated with changes in the relative abundance of two dominant bacterial divisions, Bacteroidetes and Firmicutes [26]. Overweight and obese humans have been shown to have a higher relative Firmicutes abundance than lean individuals [27]. High-fat vs. low-fat diets have been shown to associate with distinct differences in gut microbial profiles [28]. High-protein diets are associated with increased levels of uremic toxins, metabolites produced by proteolytic bacteria, such as trimethylamine-N-oxide (TMO) [29], a microbial-generated metabolite of choline and phosphatidylcholine. High TMO blood levels have been linked to increased cardiovascular risk [29, 30]. In a study comparing the gut microbiome of people eating an entirely animal-based diet (high protein) to one that was completely plant based (lower in protein and higher in fiber), those eating the animal-based diet had higher levels of Proteobacteria and fewer Firmicutes than those eating the plant-based diet. Interestingly, the investigators discovered that 1 day on either diet was sufficient to shift the gut microbiome profile [19]. Higher- vs. lower-fiber diets in general are associated with changes in gut microbiota. Studies tend to show a higher proportion of Firmicutes with higher-fiber diets in addition to lower numbers of Lactobacillus [14].

In addition to macronutrients, dietary micronutrients and other plant-derived compounds have been found to influence the microbiome, and these effects are currently an area of heightened interest, if not debate, among biomedical researchers. For example, while a gluten-free diet in patients with celiac disease promoted the growth of Bifidobacterium populations in one study [31], it was associated with lower levels in another [32]. Bifidobacteria are thought to reduce intestinal inflammation, so understanding of their modulation by gluten and/or other plant-derived components is important for many patients with intestinal disorders not limited to celiac. In patients with generalized irritable and/or inflammatory bowel problems, a dietary strategy used with increasing clinical prevalence is a diet low for fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs), touted for its purported ability to reduce symptoms associated with these bowel disorders (e.g., bloating, abdominal pain, diarrhea, constipation) [33]. By default, this diet is frequently low in fiber. But its effect on healthy gut bacteria, such as Bifidobacterium and other species, is controversial. Inulin and fructo-oligosaccharides, which are typically limited in the low FODMAP diet, have been shown to increase Bifidobacterium populations; their restriction may reduce it [34]. But other evidence suggests that long-term restrictive diets, especially those lower for carbohydrates such as low FODMAPs, detrimentally alters gut microbiota and contributes to dysbiosis [35], which could actually worsen symptoms related to irritating bowel symptoms.

Certain gut microbiota is being investigated as a source of systemic inflammation in various disease states, including chronic kidney disease [36]. Patients with kidney disease frequently have a predominance of bacteria that possess urease-, uricase-, indole-, and p-cresol-forming enzymes. The presence of these bacteria can cause increased bacterial metabolism of urease to ammonia [37], which erodes the epithelial barrier. In patients with kidney stones, much attention has been placed on Oxalobacter formigenes (O. formigenes) [38], an obligate oxalate user that resides in the colon. Studies have shown that many people who form kidney stones do not have high levels of this bacterium in their digestive tract [39, 40]. Whether this is diet related has not yet been clarified, but antibiotics appear to have a major effect on O. formigenes [41, 42]. Indeed, reduced recolonization rates after antibiotic therapy are noted [43]. A few other species of intestinal bacteria, including strains of Lactobacillus and Bifidobacterium [44, 45], are also capable of consuming oxalate and have recently been shown to carry the same oxalate-degrading genes as O. formigenes [46]. Dietary patterns that enhance these bacterial species may thus be beneficial for patients who form calcium oxalate stones; studies are needed to confirm this.