Metabonomic alterations as a result

Metabonomic alterations as a result of antibiotic use are important in the context of CDI (Theriot et al., 2014). As an example, primary and secondary bile acids have markedly different effects on C. difficile; primary bile acids promote growth of this pathogen while secondary bile acids are inhibitory. Thus, an antibiotic-induced perturbation that reduces secondary bile alkaline phosphatase inhibitors production can promote CDI (Theriot et al., 2016). In addition, mucosal carbohydrate concentrations, which can increase when antibiotics are present, can promote C. difficile expansion (Ng et al., 2013). The standard treatment for CDI is metronidazole or oral vancomycin, which kill C. difficile, providing symptomatic relief and allowing restoration of colonization resistance (Surawicz et al., 2013). However, in approximately 25–30% of cases, persistent C. difficile (as endospores) or introduction of a new strain can lead to disease recurrence, which is more likely when there is incomplete recovery of the gut microbiota (Cornely et al., 2012). Management of recurrent CDI (rCDI) is a major clinical challenge; patients that are non-responsive to antimicrobial therapy require alternative treatment options (Lapointe-Shaw et al., 2016).
Gut Dysbiosis in Ulcerative Colitis (UC) UC, a form of IBD, is a chronic, relapsing, idiopathic, inflammatory disorder of the colon and rectum (Bouma and Strober, 2003). In the last decade, there have been increases in UC incidence and prevalence worldwide, making it an important emerging global disease (Molodecky et al., 2012). Although the pathogenesis of UC is complex, multifactorial, and not fully understood, aberrant host immune responses, a dysfunctional intestinal barrier, and gut microbiota dysbiosis have been associated with this condition (Lepage et al., 2011; Michail et al., 2012). Various studies have demonstrated a reduction of gut microbial diversity and taxonomic compositional differences in UC patients compared to healthy individuals, although less stereotypical trends are observed in taxonomic variation in comparison with CDI patients (Table 1). Notably, UC has been associated with decreases in species within the Lachnospiraceae family, and Faecalibacterium prausnitzii (Lepage et al., 2011; Rossen et al., 2015). As known butyrate producers, their reduction may account for the depletion of this SCFA observed in some UC patients (Lepage et al., 2011). Additionally, Akkermansia muciniphila, a commensal gut microbe that contributes to the homeostatic balance of the intestinal mucus layer was found to be reduced in UC patients (Png et al., 2010) potentially resulting in decreased mucosal thickness corroborating histologic findings in rectal biopsies from active UC patients (Pullan et al., 1994). Driven by observations of gut microbial dysbiosis in UC, there is interest in the development and application of microbiome-based therapeutics for this indication.
Gut Dysbiosis in Obesity Obesity is a severe worldwide public health issue that has reached epidemic status in many industrialized countries (Villanueva-Millan et al., 2015), and is defined as the accumulation of excess adipose tissue to the detriment of health (Boulange et al., 2016) defined as a body mass index (BMI)>30 in adults. Dietary intake is a principal contributor to the pathophysiology of obesity, however, gut microbes can modulate nutrient uptake and energy regulation providing an important, albeit underexplored environmental factor in metabolic syndrome and obesity-related disorders (Boulange et al., 2016). The connection between obesity and the gut microbiome is complicated by heterogeneity of patient diet, genetics, age, lifestyle, hormones, and disease as well as the complexity of clinical presentation of metabolic disorders (Boulange et al., 2016). The gut microbiome has been implicated as an important player in obesity following the seminal discovery that the ratio of Firmicutes to Bacteroidetes (F:B), and energy harvest capacity differs in obese versus lean animal and human subjects (Ley et al., 2006; Turnbaugh et al., 2009). However, other studies of this link have provided conflicting results (Duncan et al., 2008; Fernandes et al., 2014; Schwiertz et al., 2010), thus, currently, there is no consensus of the importance of the F:B ratio as an indicator of obesity. In spite of this, many groups have found that both obese animal and human subjects have an altered gut microbiota compared to their lean counterparts characterized by reduced bacterial diversity, and altered colonic fermentation potential (Fernandes et al., 2014; Le Chatelier et al., 2013; Schwiertz et al., 2010; Teixeira et al., 2013; Vrieze et al., 2012) (Table 1). Metagenomically, the gut microbiome can be classified into two groups: high gene count (HGC) or low gene count (LGC). The HGC group, most often seen in lean individuals, was associated with increased F. prausnitzii and butyrate (SCFA) levels, while the LGC group, most often seen in obese individuals, was associated with lower butyrate production, but higher levels of Bacteroides spp. and Ruminococcus gnavus and more genes putatively associated with pro-carcinogenic metabolite production and oxidative stress (Le Chatelier et al., 2013). Diet-induced weight loss interventions in the LGC group could partially restore these metabolic changes, illustrating the plasticity of the gut microbiome and the significant impact of diet in obesity-related diseases (Cotillard et al., 2013).