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   Nutritional value of food depends critically upon gut of the eater   
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   science_nov._20_2015.jpg   
   By Anette Breindl    
   Senior Science Editor   
      
   Researchers from the Israeli Weizmann Institute have reported data that   
   suggest general dietary recommendations may be of limited utility, because   
   individuals vary enormously in their blood glucose response to any given food.   
      
   However, using a combination of individuals' responses to certain foods and   
   the compositions of their microbiome, it was possible to predict individuals'   
   glycemic responses and design diets that significantly reduced swings in blood   
   sugar.   
      
   The study, which appeared in the Nov. 19, 2015, issue of Cell, "offers a   
   distinct new look at nutrition, and how it affects our bodies, our microbiomes   
   and, consequently, our health," co-corresponding author Eran Elinav told   
   reporters at a press    
   conference.   
      
   It also suggests both therapeutic possibilities for targeting the microbiome   
   directly, and diagnostics that could improve clinical trials for drugs aimed   
   at metabolic disorders and possibly, other types of disorders as well.   
      
   The paper "shows the power of this type of big data and the need to do this   
   kind of work," Karim Dabbagh told BioWorld Today. Dabbagh is the chief   
   scientific officer of Second Genome Inc., a company focused on therapeutics   
   development based on an    
   understanding of the microbiome.   
      
   The work now reported in Cell represents a possible starting point for that   
   kind of work.   
      
   The study is "all correlation at this point," Dabbagh said. "But there are   
   some very clear correlations" between the presence of certain bacteria in the   
   microbiome, and appropriate glucose control.   
      
   One of those bacteria is Eubacterium rectale, and Dabbagh said one approach   
   that might be taken from a therapeutics development standpoint would be to   
   understand mechanistically what Eubacterium rectale is doing or producing that   
   might have a positive    
   effect on glucose control, and then mimic that effect "in the form of a drug,   
   not a live bacterium."   
      
   But the findings could be used in myriad different therapeutic and diagnostic   
   ways.   
      
   Dabbagh noted that in the short term, the complexity that is added by the new   
   findings might seem like one more headache for drug development.   
      
   On one level, "the paper is a really elegant analysis of the obvious, which is   
   that everything you do in life affects your health," he said.   
      
   With 800 patients and more than 100 parameters, it's also "a pretty heroic   
   study."   
      
   The work demonstrates that in any trial of 800 patients, "there are a fair   
   amount of patients that are not going to behave the way you expect them to" -   
   and furthermore, that this is probably the case with every regulated process,   
   "which is basically    
   everything."   
      
   Having a way to predict those responses means that "you can now start thinking   
   about much better drugs for the right individuals." This is also true during   
   drug development, where a way to predict responses could lead to better ways   
   to recruit and    
   stratify patients.   
      
   A MULTITUDE OF MEASUREMENTS   
      
   Elinav said that the paper suggests that "a fundamental change from the way   
   we've all viewed nutrition in the past few decades" is in order.   
      
   In the broadest sense, the paper suggests that the effect of a food is not an   
   intrinsic quality of the food itself. Instead, the most informative approach   
   is to find ways to measure, and ultimately predict, individuals' responses to   
   foods.   
      
   "In our studies, these [responses] seem to be of much more potential" for   
   understanding what a healthy diet would consist of for an individual, Elinav   
   said.   
      
   Previous small studies had suggested that not every individual has the same   
   blood sugar response to each food, and so Elinav, co-corresponding author Eran   
   Segal and their teams decided to look at such responses both in a larger   
   cohort - their study    
   included 800 subjects, none of whom had diabetes but many of whom were   
   prediabetic - and in greater depth.   
      
   They decided to focus on blood glucose levels, and more specifically on what's   
   called the postprandial glucose response (PPGR) - the change in blood sugar   
   levels that occurs within the first two hours after consuming a meal - for   
   both scientific and    
   practical reasons.   
      
   Multiple studies have shown that a PPGR characterized by spikes in blood sugar   
   is a risk factor for diabetes, obesity, and other components of the so-called   
   metabolic syndrome, a group of measures that collectively predicts high risk   
   for cardiovascular    
   disease.   
      
   Many things about the PPGR are also easy to measure.   
      
   "Within a short time we can obtain many different measurements of what we   
   would refer to as healthy nutrition," Segal told reporters.   
      
   Measure they certainly did. The team subjected study participants to Big   
   Brother-like surveillance for a week, measuring more than 100 physiological   
   parameters, including blood glucose levels at five minute intervals, and   
   detailed information about any    
   and all food consumed, including both standardized meals and the regular diets   
   of the participants (with ingredients weighed on investigator-provided scales).   
      
   They also collected blood samples and information about sleep schedules,   
   exercise and various stressors.   
      
   Finally, they looked at the microbiome compositions of their study   
   participants. In the larger initial group of 800 patients, that look took the   
   form of a snapshot. In a smaller replication cohort of 26 individuals, the   
   team repeatedly measured the    
   microbiome to identify changes over time that correlated with the responses to   
   food.   
      
   They found that whether a food led to blood sugar spikes was not an absolute   
   quality, but one that depended on the eater, with the eater's microbiome   
   playing a major role.   
      
   Though the project was conceptualized and conducted as basic research, the   
   Weizmann Institute is in licensing discussions with several commercial   
   entities who hope to develop diagnostic tests that could make individualized   
   recommendations for what is a    
   healthy diet.   
      
   Segal said that although his team cast a very wide net in their physiological   
   measurements, "we believe that there is a much more minimal set of features   
   that one can strive for. . . . Intuitively, we believe that the microbiome   
   would hold much of the    
   key to being able to make these predictions."   
      
      
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