**9.4 Application and development of the GA-map assay for diagnostic purposes**

We are currently adapting the GA-map assay for detection of the human adult core microbiota, as defined by (Arumugam, et al., 2011). This will enable an assay for the normal gut microbiota, and in identifying the gut microbiota enterotypes. We foresee that, in addition to disease-specific diagnosis, such an assay could potentially be valuable for the pharmacutical industry in population stratification in clinical trials. This tool could also be used by the food industry to determine whether their pro- prebiotic products have an impact on the normal gut microbiota.

#### **9.4.1 IBD**

Diagnostic of IBD is an important target for the GA-map assay since there are established correlations between gut microbiota composition and disease. The intention with the assay would be early detection of IBD, and potentially in the following up of IBD treatments. Alternatively, it can be used to rule out IBD from IBS patients. In the future, given a causal relation between gut bacteria and IBD, knowledge about the microbial composition could be used in disease treatment. Preliminary data using a very limited probe-set illustrates that it should be possible to develop IBD diagnostics using the GA-map technology (Frøyland, 2010). The assay is currently being refined by the addition of more probes, and through validations on clinical material. Since we are using feces and not mucosal samples in our analysis we were surprised to obtain the relatively high specificity for CD.

#### **9.4.2 NEC**

The GA-map assay is also currently being evaluated for the analysis of NEC. NEC is a very severe disease where rapid and precise diagnostics are crucial. As for IDB there are already established correlations between gut microbiota and the disease. Furthermore, for this disease there are currently no good diagnostic approaches. Preliminary data show promise for separation NEC samples from that of controls. The aim is to further improve the assay and model in order to develop a prognostic assay for NEC development. Such a test would be of great help for pediatricians and neonatologists working with pre-term infants as a guide in treatment regimes.

High E. coli and staphylococci abundance predict an early age, while for the bacteroidetes and B. breve a medium abundance predicts a high age (Fig. 7 B and D). However, very high abundance predicts an early age. The Clostridium probe, on the other hand, shows a

Figure 7 shows that the age can be modelled with high accuracy from the microbiota composition.We found that the observed and modelled age gave a squared regression coefficient of 0.6. These results show that the development of the human gut microbiota is very structured with age, and that it can be predicted. The consequence is that it could potentially be possible to determine the normal development of the microbiota in infants, and use deviations from the normal pattern in identifying disorders. For instance, from our results we can conclude that high levels of staphylococcus for older children would clearly indicate some kind of deviation form the normal development, and indicate some kind of

**9.4 Application and development of the GA-map assay for diagnostic purposes** 

We are currently adapting the GA-map assay for detection of the human adult core microbiota, as defined by (Arumugam, et al., 2011). This will enable an assay for the normal gut microbiota, and in identifying the gut microbiota enterotypes. We foresee that, in addition to disease-specific diagnosis, such an assay could potentially be valuable for the pharmacutical industry in population stratification in clinical trials. This tool could also be used by the food industry to determine whether their pro- prebiotic products have an

Diagnostic of IBD is an important target for the GA-map assay since there are established correlations between gut microbiota composition and disease. The intention with the assay would be early detection of IBD, and potentially in the following up of IBD treatments. Alternatively, it can be used to rule out IBD from IBS patients. In the future, given a causal relation between gut bacteria and IBD, knowledge about the microbial composition could be used in disease treatment. Preliminary data using a very limited probe-set illustrates that it should be possible to develop IBD diagnostics using the GA-map technology (Frøyland, 2010). The assay is currently being refined by the addition of more probes, and through validations on clinical material. Since we are using feces and not mucosal samples in our

The GA-map assay is also currently being evaluated for the analysis of NEC. NEC is a very severe disease where rapid and precise diagnostics are crucial. As for IDB there are already established correlations between gut microbiota and the disease. Furthermore, for this disease there are currently no good diagnostic approaches. Preliminary data show promise for separation NEC samples from that of controls. The aim is to further improve the assay and model in order to develop a prognostic assay for NEC development. Such a test would be of great help for pediatricians and neonatologists working with pre-term infants as a

analysis we were surprised to obtain the relatively high specificity for CD.

complex association with age.

impact on the normal gut microbiota.

diseased state.

**9.4.1 IBD** 

**9.4.2 NEC** 

guide in treatment regimes.


Table 1. Single probe GA-map diagnostics of CD (Frøyland, 2010)

#### **9.4.3 Test for assessing health condition of individuals**

Many medical doctors find that an analysis of a patients gut microbiota is helpful in obtaining a more complete picture of the condition of the patient, and thus determining the disease state and best treatment. Several such tests exists in the marketplace. The GA-map technology is positioned to become a very powerful test for this purpose, with its complex probe selection and high through-put capabilities.

The general process for the application of the GA-map assay for diagnostic purposes is illustrated in Figure 8.

After implementation of the pilot diagnostic assays, new approaches and diseases will be implemented under the GA-map umbrella. There will also be a transformation over time towards decentralized analyses.
