#115: Ian Spreadbury, PhD- Ancestral Carbohydrates VS Acellular Carbs and Gut Bacteria

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About Ian

Ian is currently in medical school in Québec, but was formerly a scientist at the Gastrointestinal Diseases Research Unit, Queen's University, Kingston, Ontario, Canada

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Show Notes

Mike: Since your revolutionary paper in 2012, do we have a better understanding as to why acellular carbohydrates (i.e., processed grain and sugar-derived carbohydrates) are more detrimental to the gut microbiome and thus metabolic health of Westerners compared to the cellular carbohydrates (i.e., grain-free whole foods such as tubers) that our ancestors ate?

Ian: I’ve scrawled the following in answer to your questions. I hope these help let you know where my thoughts are, a few years on from the 2012 paper 🙂

I should initially point out that sadly I haven’t been able to do any research on this myself, as I’m not a principal investigator. A few things have come along to support the core of the hypothesis. Alan Cooper’s group from Adelaide published a paper in Nature Genetics in 2013 looking at the microbiota sequenced from dental tartar of human skeletons. This showed profound shifts in the makeup of the oral microbiota with the onset of farming (advent of periodontitis-associated pathogens), and also later around the time of the industrial revolution (cariogenic bacteria and diversity collapse). The authors themselves attributed these changes to the arrival of flour and refined sugar, respectively, in the human diet. This was the first demonstration that changing levels of acellular carbohydrates were associated with pathophysiological changes in the microbiota of a part of the gut.

Slightly before that came the very intriguing study (by Desmarchelier) showing that powdered foods produced far more metabolic perturbation and weight gain in mice than hard chows made of the same material. Really interestingly, the highly powdered versions of foods of varying macronutrient makeup all produced identical changes, with the caloric intake of the mice converging at the same high level. These mice “knew” to eat slightly less of the high-fat chow (by weight) to get the same caloric intake. This work really intrigued me as this looks like a perturbation of energy homeostasis; and it’s one that seems macronutrient independent, which is interesting if you were trying to explain it by insulin or other means invoking only mammalian physiology.

There have also been many papers since highlighting the importance of elements of the immune system and T regulatory balance in animal and human obesity and metabolic problems. I’m excited about this angle of evidence, as the GALT (gut-associated lymphoid tissue) houses most of the immune system and is also the digestive absorption route for dietary fat. So, one can presume that everything that passes that way gets vetted by the immune system. This means the immune system is in the right place to act as a sensor of microbial changes emerging from the gut. From there, it could produce much of the early inflammatory processes that are perturbing vagal function in obesity. Disruption of the T regulatory balance might then play a role in wider systemic immune dysregulation, inflammation and autoimmunity in the susceptible. Finally, the immune system is a tempting candidate to provide the “memory” element to obesity in remission—the reason that a formerly overweight person who has been eating an “ancestral diet” for years can still get hit by hunger and weight gain after introducing even small amounts of Western foods.

Mike: What is your favorite cellular carbohydrate?

Ian: Probably sweet potatoes. They’re readily available, quick and easy (with microwave assist). Some potatoes are on my menu, but I’m trying to figure out which strains leave me with a headache after a few days. Some do, some don’t. I eat a lot more beans than some would expect. I don’t seem to react in any way to most of the common beans. Edamame and peanuts invariably do bad things to my knuckles though. I imagine legumes have lectin issues, not density bad-bugs issues.

Mike: The whole-food carbohydrates that our ancestors consumed often had a myriad of polyphenolics that have recently been shown to exert protective effects on the diversity and composition of the gut microbiome. What is your take on polyphenolic rich foods? Any specific mechanisms or new developments that we should be aware of?

Ian: My starting point is one of skepticism regarding antioxidants and other isolated components of real foods as being usefully protective or restorative against Western disease. We’ve seen a long-running conviction that somehow the complex chemical makeup of real foods is what bestows the health of an exclusively real-food diet, and this has launched a lot of clinical trials to test these elements, as well as countless supplements and putative “superfoods” for being rich in something or other.

The tests of these compounds may occasionally generate a small statistically significant difference in a study, but no one’s showing transformation of metabolic health or remission from obesity from any of these phytonutrients or other chemicals alone. That kind of real-world change only appears when you exclude all the “bad” foods.

I view fruit and veg as “safe” ways to get calories and micronutrients into the system without starting an inflammatory bug party in the upper gut. Broadly, I’d say there are no foods that are “good for you”–only foods that are neutral and foods that are bad. We’ve got no real evidence yet for a superfood or supernutrient that’s going to protect you from eating cakes if you’re in remission from obesity or have underlying Western disease processes going on. Of course, it’s possible we’ll get lucky and find something that really helps, but it would surprise me. I don’t doubt that the additional chemical complexity in real food allows a measurably more diverse and complex GI microbiota to form—a difference big enough to put an asterisk over in a paper. I don’t however think the difference to what’s going on in western disease is large enough to make a real-world difference, as we’d have seen a larger benefit from supplementing with fruit and veg or pills in clinical trials if this worked reliably via any means.

Mike: Do you have a favorite gut friendly, polyphenolic-rich whole food?

Ian: I’m afraid not J

Mike: Our understanding of dietary fat has evolved as well. You say fat is an execratory, but not primary, cause of obesity. Is the main problem with fat due to its inherent ability to transport bacterial particulate, such as endotoxin, into the blood stream?

Ian: It’s possible there’s some more recent research on this that I’ve missed. The microbiome is a vast and growing field. LPS is certainly not a helpful thing to have leaking from your gut, but it’s almost certainly too simplistic an explanation by itself. The overall assessmentof the gut-associated lymphoid tissue’s immune system makes of the microbial situation in the gut is likely, in my mind, to be the key.

The GALT deals with the lipid absorption from food, so elevating dietary fat could conceivably bring the bug party and the immune police together in a way that worsens the problem, but perhaps only if there’s a pre-existing unnatural carb-based bug party underway. The other possible role of fat as part of a Western diet might be to stabilize whatever ecosystem phenomena, microbial behaviors, or species are triggering the inflammatory changes. This plays into your next question.

Mike: Are there any precautions one should consider when consuming a high-fat diet (i.e., in the context of nutritional ketosis) so as to minimize the potential impact on the gut microbiome?

Ian: Since higher fat ancestral diets seem well-coped-with by the peoples who eat/ate them, perhaps the best advice for someone who has decided to eat a higher fat diet would be to consume fats only as part of a real-foods diet. The more processed, refined, or evolutionarily novel the preparation of fats is, it seems the more likely it might have unexpected adverse effects on the microbiota. I certainly wouldn’t advise guzzling refined fats to hit some calculated proportion, and I haven’t (yet) been convinced that ketosis itself mechanistically leads to sustained weight loss.

Mike: As a follow up and related question, intestinal-derived leptin resistance is a new topic for many; do you feel that metabolic endotoxemia (i.e., gram-negative bacterial particulate leakage) and associated changes in cytokine signaling is a main driver of so called “leptin resistance”?

Ian: LPS itself? Not really, no. I did try to spell this out in the 2012 paper, but had to mention LPS a lot– as it’s what the people I thought would likely be peer-reviewing the paper were all working on at the time. So, it was science politics in a way. Circulatory LPS changes are a proxy for possible microbial changes and gut leakiness. There are putative TLR4 pathways that could account for some of the reported changes in leptin sensitivity, and to be sure LPS is not a good thing. However, there was already evidence in humans that low-fat diets could produce marked drops in circulating LPS. If LPS was the main cause of leptin-sensitivity changes, low-fat diets ought to be highly effective and reduce hunger. Of course, they aren’t and they don’t.

The actual mechanisms linking Western-style acellular carbohydrates, microbial changes and the vagal and hypothalamic changes underlying obesity are of course as of yet unresolved. The circumstantial evidence is quite compelling, but no one’s fingerprinted the culprits and connected them end to end yet.

One good candidate however is the immune system, as I mentioned earlier. The GALT’s immune system will take a complex approach to assessing the threat from the gut, and somewhere along the line might raise the alarm, initiating the inflammatory changes that lead to overweight or diabetes or to autoimmunity or other inflammatory conditions. The exact point where that alarm gets raised, and what its effects are, apparently varies from individual to individual. Animal experiments indicate there are a lot of microbial changes with obesogenic diets that occur even in obesity-resistant animals, and some more that are seen in the obese.

I suspect that with western diets the causal changes in microbes may already have occurred even in the lean, and that the immune system’s disposition to react or not may determine the host response. The additional microbial changes seen in the obese may well be the result of obesity or increased food intake feeding back onto the microbiota.

Mike: Are there any whole-food substances or lifestyle practices that we should know of that may best ameliorate this diet induced shift in our leptin signaling pathways?

Ian: I think the best advice is to keep eating real foods without processing or grains, flour, or sugar, and avoid cheat days or indulgence foods. If the hypothesis is correct, and microbial changes are upsetting the immune system, there’s good reason to try our best to stay on the straight and narrow. Immune systems can sensitize to ongoing or repeated presentations of antigenic materials. We shouldn’t be showing them this stuff to give them ideas. Also, bacteria tend to win adaptive evolutionary races and share their genes with each other to spread new angles on things. They can get “better” at exploiting niches. We shouldn’t give them practice by exposing them to half-measure diets.

Fasting or intermittent fasting might have some of its reported effects by helping break stubbornly locked-in ecosystem changes by “draining the swamp” of the Western gut. However, it obviously only has benefits for the long-term if one follows the fast with a good ancestral diet (see above). I don’t think there are any magic bullets; we can’t “con” either a microbial ecosystem or immune systems into behaving naturally, except by exposing them to only natural unprocessed real cellular foods.

Mike: Are there any new or emerging discoveries that have you particularly excited at the moment (related to nutrition/gut bacteria)?

Ian: Exciting things that are starting to appear in the literature include this whole field of bacterial colonization of mammalian hosts and the putative role of biofilms and similar in chronic diseases. It’s early days yet (and I must stress this), but there’s emerging evidence that Alzheimer’s disease may be associated with manifold elevations of number and diversity of periodontal pathogens in the brain.

The scientists researching this field are intrigued by the order of symptoms often seen in AD, which appear consistent with the route an oral pathogen would traverse to enter via the olfactory bulbs. The risk-elevating APOE4 polymorphism has been reported to increase blood-brain barrier permeability, and it is being suggested that amyloid may be an attempted anti-microbial defense.

As I say, early days yet, but you can see why the MDs in this field have reportedly become keen flossers and brushers. I’d suggest they’d be much better off eating in a manner styled to pre-date the arrivals of flour before many of the periodontal pathogens apparently arrived in the human mouth (see Adler, Cooper et al 2013 Nature Genetics).

On another note, I should also point out the nice, recent paper highlighting obesogenic and proinflammatory changes produced in mice by realistic levels of the artificial emulsifiers Polysorbate 80, and carboxymethylcellulose. These things are in quite a lot of processed foods and have altered the microbiota and compromised barrier function by reducing the thickness of the mucous layer produced by the gut wall. These are another example of how being creative with food has influenced a crucial ecosystem with great power over its host in ways we’re only just beginning to appreciate. Western diets full of refined carbohydrate, artificial emulsifiers, and a payload of lectins really are the perfect storm.