**3. Function vs phylogeny of gut bacteria**

A long standing debate is how well functionality of bacteria in the gut correlates to phylogeny. There are recent reports suggesting that the function of gut bacteria is a relatively stable feature, while the microbiota composition is unstable (Turnbaugh et al., 2009).

Although functions cannot directly be deduced from the gut microbiota 16S rRNA gene analyses, correlations between gut microbiota phylogenetic composition and function can be established. We have recently addressed this issue by mapping functions onto a phylogenetic map as illustrated in Figure 1. As seen in this figure, there are good correlations between functions and phylogeny, with different functions being clustered in different phylogroups.

The take home message from this analysis is that the phylogenetic framework can be used to deduce the probability of functions in the gut microbiota, and aid in identifying functions through other targeted approaches. Still, however, our knowledge about the correlations between function and phylogeny is limited. The current major genomic sequencing efforts will aid in these investigations. It will be particularly interesting to determine which functions follow a phylogenetic distribution pattern, and which do not.

For genes located on mobile elements, such as those encoding antibiotic resistance, an important aspect would be to determine the host range of the mobile elements. For instance, given that there are antibiotic resistance genes present on mobile elements in the commensal microbiota with a host range that include pathogens, there will be a severe risk that the antibiotic resistance genes can be transferred to the pathogen.

Gut Microbiota in Disease Diagnostics 105

Necrotizing enterocolitis (NEC) (Wang et al 2009) and inflammatory bowels disease (IBD) (Frank et al 2007, Nell et al 2010) are two diseases that have a recognized established link to

NEC is a severe disease affecting preterm infants with a high mortality. About 10% of infants with a birth weight below 1500 g develop NEC, with mortality rate is as high as 30%. It has been suggested that this disease is associated with a reduced diversity of the gut microbiota (Wang et al 2009). Both due to the impact of the test, and because the preterm infant gut microbiota is relatively simple, NEC is an attractive target for developing a

IBD represents a collection of diseases associated with gut inflammation. It has two main sub forms: Crohn's Disease (CD) and Ulcerative colitis (UC). Disturbance of the normally stable GI microbiota are predicted to adversely affect the health of the host (Frank, et al., 2007). Studies of experimental animal models of IBD reveal that germ-free animals show few signs of inflammation; experimental colitis is exhibited only when the animal is exposed to natural microbial communities. Likewise human studies have shown a response of IBD patients to antibiotic and probiotic treatment (Hecht, 2008). In CD patients inflammation most commonly appears in the gut locations where bacterial concentrations are high. Furthermore, diversion of the fecal stream from the lumen is associated with improvement of the inflammation, indicating a role for bacteria in the IBD pathogenesis (Baker, Love, & Ferguson, 2009). Taken together, there are relatively good evidence for a correlation between

There is a very wide range of diseases that have been suggested correlated to the gut microbiota. Among these are diabetes, cardiovascular diseases, rheumatism, metabolic syndrome and obesity (Wang et al. 2011, Wen et al., 2008, Ley et al., 2006). Common for most of these diseases is the correlation to some form of underlying inflammation. Thus, imbalance in the gut microbiota could be a common underlying factor that triggers

Future knowledge building with respect to microbiota composition could open new diagnostic possibilities for these diseases, which all have major impacts on human health. Gut microbiota diagnostics may also help in understanding the etiology of the disease,

The perhaps most surprising correlation to the gut microbiota are cardiovascular disease (Wang et al. 2011). There were relatively strong correlations between microbial metabolites and atherosclerotic disease. Gut microbiota diagnostic in this field could potentially have

Major diseases with more diffuse symptoms such as irritable bowels disease (IBS) (Salonen et al 2010) and depression (Maes et al 2009) could be targets for development of future

inflammation. Still, detailed knowledge is lacking about such potential correlations.

**4. Diseases with established correlation to the gut microbiota** 

**5. Diseases with suspected correlation to gut microbiota** 

which potentially could help in developing therapeutic approaches.

**6. Gut micobiota diagnostic for diffuse conditions** 

the gut microbiota.

human gut microbiota test.

IBD and the gut microbiota.

major impacts on human health.

Fig. 1. Properties of gut bacteria in a phylogenetic framework. The PCA biplots represent the 16S rRNA phylogenetic relatedness between the bacteria, while the green circles represent different functions for the different panels. The six panels represent six different functional groups.

Fig. 1. Properties of gut bacteria in a phylogenetic framework. The PCA biplots represent the 16S rRNA phylogenetic relatedness between the bacteria, while the green circles represent different functions for the different panels. The six panels represent six different functional

groups.
