**8. Conclusion**

mice despite the fact they actually eat more and take in more calories which should oppose this affect [59]. Further studies in germ‐free mice have demonstrated that an obese phenotype is transmissible from mouse to mouse via the gut microbiota. Germ‐free mice receiving microbiota transplants by oral gavage with microbiota either sourced from genetically obese *ob/ob* mice or lean mice have demonstrated that recipients of the *ob/ob* microbiota put on more body fat in the weeks after being inoculated as compared to those who received the "lean" microbiota transplant [60]. 16S‐rRNA‐gene‐sequence‐based analysis of samples obtained in this study demonstrated that the *ob/ob* donor microbiota samples had a greater abundance of firmicutes bacteria compared with that of the lean donor microbiota samples [60] indicating the possibility that enriching the gut with firmicutes may drive the body weight phenotype. Indeed a number of rodent studies have raised the possibility that the ratio of the phyla bacteroidetes to that of the phyla firmicutes is associated with obesity. In comparison with lean mice, *ob/ob* mice have a ~50% reduction in the abundance of bacteroidetes and an increase in firmicutes [61]. High‐fat feeding studies utilised to induce obesity via a dietary means also have found an increase in the firmicutes species [62] indicating that both obesity induced by hyperphagia (*ob/ob* mice) and obesity induced by energy dense food (high‐fat diet) is associated with an increase in firmicutes. As differences in gut microbiota communities may impact obesity and the metabolism of the host mouse, this should be considered a confounding factor when comparing different mouse strains, or the same mouse strain but from different mouse vendors or animal facilities as each facility is likely to harbour its own unique microbiota

**7.3. How would the gut microbiota cause obesity or contribute to obesity progression?**

There are many possible reasons as to why the gut microbiota composition may impact the host and result in the development of obesity. First, certain types of gut microbiota may be more efficient in extracting energy out of food that passes through the gut and therefore make available more energy for the host in which they reside. Bomb calorimetry analysis measuring the energy content of faeces revealed that *ob/ob* mice have significantly less energy remaining in their faeces relative to their lean littermates suggestive that the microbiota within *ob/ob* mice are better at harvesting and extracting energy from the food within their digestive tract [60]. Other possibilities include the role of inflammation. Obesity has been associated with a type of chronic low‐grade inflammation and modification of the gut microbiota has been suggested to increase the leakiness of the gut barrier resulting in the increased appearance of microbial products such as lipopolysaccharide (LPS) (endotoxin) in the circulation [63, 64]. These products could potential cause peripheral tissue inflammation and impede normal metabolism. Yet another possibility is the fact that the gut microbiota is responsible for the production of metabolites such as short‐chain fatty acids (SCFAs) that are produced by the fermentation of dietary fibres by the bacteria in the gut [65]. SCFAs are organic acids with an aliphatic tail of less than six carbons and comprise of acetate, propionate, butyrate and valerate and are used by the host as an energy source. It is hypothesised that alterations in the production of these SCFAs with obesity could adversely affect satiety, hepatic glucose and lipid production as well as inflammatory processes and contribute to the progression of obesity and related conditions [66]. Thus, the microbiome composition can have an impact

signature.

40 Adiposity - Omics and Molecular Understanding

Herein, we have provided a review of the information that has been sourced from the study of the various"omes" in relation to obesity—from the genome and epigenome that provided the initial coding information regarding body weight regulation right through to the functional"omes" the proteome and metabolome that carry out the physiological cellular functions of these codes. As further investment is made in technologies to increase the capability and detection of these"omic" molecules, a multi‐disciplinary team approach will be required to extract the most information and perhaps more importantly, the most relevant physiological information in relation to obesity. A systems biology approach is needed to understand the complexity of the physiology of all the reactions that take place due to the interaction between all of the genetic, proteomic and metabolomic information. Engineers are vitally important in furthering the technological capacities of machinery and bioinformaticians in developing ways to explore these complicated data sets to ensure that the data are collected and analysed in a meaningful way. Graphical representation of the data in a digestible fashion is essential to foster understanding of these findings of scientists of different fields. Cell biologists, biochemists and physiologists will play an important role in characterising these findings in proof‐of‐concept experiments in laboratory, and health and medical practitioners armed with these findings will ultimately deliver knowledge and hopefully personalised treatment strategies to the obese patients in the clinic.
