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The recent availability of high-throughput nucleic acid sequencing technologies has rapidly advanced approaches to analysing the role of the gut microbiome in governance of human health, including gut health, and also metabolic, cardiovascular and mental health, inter alia. Recent scientific studies suggest that energy intake (EI) perturbations at the population level cannot account for the current obesity epidemic, and significant work is investigating the potential role of the microbiome, and in particular its metabolic products, notably SCFA, predominantly acetate, propionate and butyrate, the last of which is an energy source for the epithelium of the large intestine. The energy yield from dietary residues may be a significant factor influencing energy balance. This review posits that the contribution towards EI is governed by EI diet composition (not just fibre), the composition of the microbiome and by the levels of physical activity. Furthermore, we hypothesise that these factors do not exist in a steady state, but rather are dynamic, with both short-and medium-term effects on appetite regulation. We suggest that the existing modelling strategies for bacterial dynamics, specifically for growth in chemostat culture, are of utility in understanding the dynamic interplay of diet, activity and microbiomic organisation. Such approaches may be informative in optimising the application of dietary and microbial therapy to promote health. OverviewThe availability of high-throughput nucleic acid sequencing technologies has facilitated a range of new approaches to analysing the role of the gut microbiome in governance of human health (1) . Modern techniques suggest a role for the microbiome maintenance of, not only gut health but also systemic conditions, including cardiovascular health (2) , mental health (3) and obesity (3) . Despite wide media focus on excess energy intake (EI), recent scientific studies suggest EI perturbations at the population level cannot account for the current obesity epidemic (4) . The microbiome is responsible for the production of a highly complex and highly dynamic metaexometabolome. Well-known components of this include the SCFA acetate, propionate and butyrate, the last of which is an energy source for the epithelium of the large intestine (5) , as well as an inhibitor of histone deacetylation (and thereby cell fate determination) (6) . The energy yield from dietary residues entering the large intestine may account for as much as 10 % of EI (7) and is therefore a significant factor influencing energy balance. The guiding theme of this review is that this contribution towards EI is governed by EI, diet composition, the composition of the microbiome and levels of physical activity. Furthermore, we hypothesise that these factors do not exist in a steady state, but rather are dynamic, with both short-and medium-term effects

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Long-chain fatty acids have been shown to suppress appetite and reduce energy intake (EI) by stimulating the release of gastrointestinal hormones such as cholecystokinin (CCK). The effect of NEFA acyl chain length on these parameters is not comprehensively understood. An in vitro screen tested the capacity of individual NEFA (C12 to C22) to trigger CCK release. There was a gradient in CCK release with increasing chain length. DHA (C22) stimulated significantly (P , 0·01) more CCK release than all other NEFA tested. Subsequently, we conducted a randomised, controlled, crossover intervention study using healthy males (n 18). The effects of no treatment (NT) and oral doses of emulsified DHA-rich (DHA) and oleic acid (OA)-rich oils were compared using 24 h EI as the primary endpoint. Participants reported significantly (P ¼ 0·039) lower total daily EI (29 % reduction) with DHA compared to NT. There were no differences between DHA compared to OA and OA compared to NT. There was no between-treatment difference in the time to, or EI of, the first post-intervention eating occasion. It is concluded that NEFA stimulate CCK release in a chain length-dependent manner up to C22. These effects may be extended to the in vivo setting, as a DHA-based emulsion significantly reduced short-term EI.

Self-report ratings of appetite, particularly visual analogue scales (VAS) are commonly used to measure subjective appetite and to assess modifications thereof following an intervention (1,2) . Subjective rated appetite is a widely employed proxy measure for Actual Energy Intake (AEI) (3) , measurement of which requires greater time and resources. The validity of self-report measures of appetite as surrogate measures of AEI have not been systematically reviewed elsewhere.To identify the corpus of papers assessing both self -reported appetite and AEI in the same trial and to establish whether self-report scales reliably predict AEI.A literature search was undertaken spanning 1999 to 2015 identifying studies recording both VAS ratings and AEI, generally in response to a nutrient or food intervention. Outcomes were pre-defined as there being agreement between self-reported appetite and AEI (link) or no agreement between self-reported appetite scores and AEI (no link). The presence of statistical (direct) comparison between the two methods was also recorded, the type of intervention, subject or patient were also noted. Each paper was scored independently by two authors.462 papers were included in this review. Appetite scores failed to correspond with AEI in 51·3 % of total studies. Only 6 % of studies evaluated directly compared the two measures statistically. A Chi Squared test revealed a significant departure (P < 0·001) from observed and expected frequencies for direct assessment of a link when studies were separated by 'intervention type'. This effect appears to be, in part, due to the use of pharmaceutical interventions and particularly where satiety regulating hormones were manipulated.The very substantive corpus identified in this review allows us to conclude that self-reported appetite ratings of appetite do not reliably predict AEI. Caution should be exercised when deriving conclusions based from self -report appetite data alone in relation to prospective energy intake.

Weight loss is coupled with improvements to affective state in obese participants engaged in behavior change therapy based on incremental, selfselected "Small Changes". Nutrition Research, 31 (5), 327-337.