226 Genes Nutr (2011) 6:209–240 Table 6 Overview of human studies that demonstrate an association between extra-intestinal disease and compositional dysbiosis of the intestinal microbiota Study material Population Analytical methods References Atopic and allergic diseases Faeces 27 Allergic children Conventional culturing 36 Non-allergic children Faeces 18 Infants who developed allergy Conventional culturing (5 time points) 26 Infants who remained non-allergic Faeces 76 Infants at high risk for atopic disease Conventional culturing (2 time points) FISH Faeces 27 Infants with atopic dermatitis Conventional culturing (2/3 time points) 10 Infants without atopic dermatitis FISH Faeces 30 Children with atopic dermatitis Conventional culturing 68 Children without atopic dermatitis Faeces 957 Infants qPCR Faeces 20 Allergic children DGGE 20 Non-allergic children Faeces 10 Allergic infants qPCR (3 time points) 16 Non-allergic infants Faeces 37 Infants with atopic dermatitis TGGE 24 Infants without atopic dermatitis FISH/ﬂow cytometry Faeces 15 Infants who developed atopic dermatitis T-RFLP 20 Infants who remained without atopic dermatitis TGGE Faeces 16 Infants who developed allergy qPCR (3 time points) 31 Infants who remained non-allergic Bjo¨rkste´n et al. (1999) Bjo¨rkste´n et al. (2001) Kallioma¨ki et al. (2001) Kirjavainen et al. (2001) Watanabe et al. (2003) Penders et al. (2007) Sˇ tsˇepetova et al. (2007) Suzuki et al. (2007) Gore et al. (2008) Wang et al. (2008) Sjo¨gren et al. (2009) Finegold et al. (2002) Song et al. (2004) Parracho et al. (2005) DGGE denaturing gradient gel electrophoresis, FISH ﬂuorescence in situ hybridisation, qPCR quantitative polymerase chain reaction, T-RFLP terminal-restriction fragment length polymorphism, TGGE temperature gradient gel electrophoresis microbiota composition and diversity to disease. Again, also for all these diseases the causality argument of the observed microbiota changes is unresolved. Ultimately, causality and knowledge of the underlying mechanisms will be crucial for a full understanding of the role of the intestinal microbiota in the aetiology of speciﬁc diseases. Autism Faeces Stomach contents Small intestine contents Faeces Faeces Faeces Diabetes type 2 Faeces Faeces Rheumatoid arthritis Faeces 123 13 Autistic children 8 Non-autistic children 15 Autistic children 8 Non-autistic children 58 Autistic children 12 Non-autistic siblings 10 Non-autistic children 33 Autistic children 7 Non-autistic siblings 8 Non-autistic children 16 Type 2 diabetic patients 12 Non-diabetic individuals 18 Type 2 diabetic patients 18 Non-diabetic individuals 51 Patients with early rheumatoid arthritis 50 Patients with ﬁbromyalgia Conventional culturing 16S rRNA gene sequencing qPCR FISH 454 FLX titanium sequencing (16S) Finegold et al. (2010) DGGE qPCR qPCR 454 FLX titanium sequencing (16S) Wu et al. (2010) Larsen et al. (2010) FISH/ﬂow cytometry Vaahtovuo et al. (2008)