Microbes, Mycotoxins, Milk Fats, and the Na:K Ratio - What's the Latest in Nutrition Science in February 2019?

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Nutrition sciences are all about the microbiome, these days. Against that background you probably won't be surprised that my brief overview of studies from the latest edition of Molecular Nutrition & Food Research features 3+1 studies that deal with the food <> microbiome <> health interaction or could at least be related to it... before we get to the details, I want to warn you, though: The way people ascribe everything to gut bugs and try to sell random probiotics to customers is not science. That's quackery!
Review older articles about the gut - health axis.at the SuppVersity

Bugs Dictate What You Crave

Sweeteners & Your Gut

Foods, Not Ma- cros for the Gut

Lactulose For Gut & Health

Probiotics Don't Cut Body Fat

Microbiome <> Bread's H. Effects
  • Harnessing the microbiome to battle the ill-effects of a more than suboptimal diet -- Several papers in the latest issue of Molecular Nutrition & Food Research address the interactions between the microbiome and the (cardio-)metabolic problems that are caused by Westernized (=high fat + high carb + high energy) diets ... all in rodents, but still interesting.

    As you may remember from previous articles and SuppVersity Facebook News, grape seed flour, formerly marketed mainly in "pump supplements", doesn't just taste like crap and is a powerful anti-oxidant but also a great antibiotic. As such it was used in a recent study that determined the separate and combined effect of a prebiotic (catechin‐rich wine grapeseed flour, GSF) and a probiotic (newly isolated kefir lactic acid bacteria, LAB) on hepatic steatosis of obese mice on a 17% protein, 37% carbohydrates, and 46% fat diet.
    Figure 1: Total lipid content (mg/g liver | left) and hepatic lipid (trigs, total cholesterol, LDL, VLDL) levers (mg/liver | right) after consumption of control, GSF, GSF+LAB, and LAB-only diet (Kwon 2018).
    As you can see in Figure 1, the provision of an albeit high amount of GSF (10% of the diet ~1.6g per day in human equivalents) had significant beneficial effects on the established fatty liver of the rodents. Effects that were not further augmented by adding the probiotic LAB in. What the scientists did observe, however, was a synergy in terms of enhanced hepatic antioxidant activities, of which they believe that it was mediated through "regulation of hepatic genes, cecum propionate production via intestinal action of LAB, and intestinal barrier function" (Kwon 2018).
Worst offenders: OTA and alert notifications in Europe - Alert notifications are sent whenever a foodstuff presenting a serious health risk to humans is identified at the internal market and whenever the rapid action of the competent authorities is required (Malir 2016).
Mycotoxins stay (in your blood) -- Study in humans shows that the mycotoxin metabolite 2′R‐OTA which is produced by mold and fungy as you can find it, e.g. in/on coffee, cereals, grains, etc., has a more than seven‐fold higher biological half‐life in human blood compared to OTA (approx. 35 days). "The reason for the long persistence of 2′R‐OTA in human blood is still unclear and further research is needed," researchers from the Westfälische Wilhelms‐Universität Münster in Germany write. The scientists also point out that the most (if not only) relevant source of 2'R-OTA in the subjects' diets was... coffee powder, which contained 6.45 ± 1.75 µg OTA per kg coffee!

How bad is that? Well, as the Germans point out, "only little is known about the toxicity of 2′R‐OTA and potential health risks related to this compound" (Sueck 2018) - hence, it could be anything from an important step in the detoxification process to the formation of a kidney-frying super-chemical ;-)
  • Figure 2: Effects of High sodium, low potassium (HNaLK) diet and on gut bacterial composition shown at the level of family or genus (Blazenovic 2018).
    The sodium/potassium (Na:K) ratio as a modulator of your guts' microbial composition and the type and amount of amines/amino acids that make it into your blood -- With the modern Western diet being characterized by excessive sodium (NaCl) and deficient potassium (K) intakes, the revelation that a high NaCl/K diet will significantly reduce the absorption of amino acids (including l-histidine and proline) as well as normetanephrine and DBPM (I honestly cannot tell you if that's good or bad news). The amount of the potentially heart-disease promoter TMAO, on the other hand, increased.

    While the specific implications of the amine elevations in the study at hand are not clear, it is obvious that the (eventually) expectable modulatory effect of the Na:K ratio in mammalian diets on their microbiome could contribute significantly to the prevalence of dysbiotic guts in consumers of the Western diet.
  • The good skin of the good 'bad fats' in milk is better - Butter, Milk, and Buttermilk - Significant anti-obesity effects is what researchers from France ascribe to the relatively small amount of polar lipids from dairy products in the context of an obesogenic diet they fed to rodents who received either a diet enriched in milk polar lipids (1.1 and 1.6% MPL1 and MPL2, respectively), naturally containing 25% of sphingomyelin, or a standard "high fat" (=high energy) diet.
MLPs, i.e. milk polar lipids, are structural components of dairy fat globules. You may have heard about the putative health benefits of phospholipids like sphingomyelin, which fall into the category of MLPs. Evidence exists for both, direct and indirect beneficial effects on heart health, metabolic health, lipid and glucose metabolism, etc.
  • Figure 3: MPL2 supplementation in high fat diet reduced body weight gain. Mice were submitted to a chow‐based high‐fat diet (HF) or a high‐fat diet supplemented with MPL (1.1% or 1.6%) during 8 weeks. A) Cumulative body weight (BW) gain evolution (Milard 2018).
    What Milard et al. (2018) found was that Male C57Bl/6 mice receiving a high-fat diet  (=high fat + carbs = obesogenic diet) without added MPLs (21% fat, mainly palm oil, in chow), gained significantly more weight than those whose diet was enriched with 1.6% HF‐MPL2 (a smaller effect was observed for 1.1% HF‐MPL1); and while the "[..d]iets [did] not impact plasma markers of inflammation but in the liver, HF‐MPL2 tends to decrease hepatic gene expression of macrophage marker F4/80 versus HF‐MPL1 (p = 0.06)" (Milard 2018) - both occurred in spite of the fact that the HF-MPL2 mice consumed the highest amounts of food.

    Table 2: Fatty acid composition of the diets (Milard 2018) |  note: the amount SFA, MUFA, and PUFA was identical
    Moreover, the provision of HF‐MPL2 (p < 0.05) seems to have highly beneficial effects on the integrity of the mammalian gut (highest colonic crypt depth with MLP2), while - surprisingly - reducing the count of Lactobacillus reuteri (p < 0.05), which correlates negatively with the fecal loss of milk sphingomyelin‐specific fatty acids (p < 0.05).

    Speaking of which, it's not clear (yet) which of the differences in the fatty acid composition of the diets (see Table 1) make the ultimate difference.

    What we do know, however, is that our best chance to get sphingomyelin from our diet are butter and buttermilk products (Bourlieu 2018). With the latter having a polar lipid content of 8.5 ± 1.1 wt% (vs. 1.4 ± 0.2) and a corresponding amount of 3.4–21 mg/g sphingomyelin (dry matter), drinking buttermilk or eating butter, alone (58 mg/100g sphingomyelin, 34mg/100g sphingolipids), probably won't get you into the supplementation zone used in the study at hand... 

  • While we're waiting for further research in human beings, it would still appear to be better than nothing to incorporate reasonable amounts of fatty dairy products into your diet (not into your coffee ;-) if you want to harness the power of sphingolipids as structural components of membranes, lipoproteins, skin, and other biomaterials, as well as cell signaling modulators and mediators.
Table 2: Phospho- and sphingolipid content of selected dairy products as determined by HPLC coupled to an evaporative light scattering detector (Rombout 2007).
Bottom line: Instead of a summary of the summaries, I thought I'd address the two questions, of which I believe that the majority of you will be asking themselves. Why exactly do I want sphingolipids and - more importantly - where in my diet can I find them? 

Let's start with the 2nd question which can be answered by the data Table 2 - good sources of our average dietary intake of 2-8 g (total) polar lipids - among that 0.3 to 0.4 g sphingolipids - per day are butter, buttermilk, ricotta, and other cheeses. Don't get confused by the relative amount of MPLs, though: Quark, for example, is extremely high in MPLs, but at a total fat content of 0.1% it's obviously not a good source of polar lipids ;-)

Ok, now that we know where to find it, it's time to (re-)address why it even makes sense to eat these special phospholipids. Well, Milard et al. point out sphingolipids "can be categorized as 'functional ingredients' because they have structural regulatory functions" (Milard 2018). Originally derived from the milk fat globule membrane (MFGM), i.e. the "skin" of milk fat, they occur in relevant amounts almost exclusively in animal products, of which dairy is by far the best source of these 'super fats' (25% of MFGM‐PL | Milard 2018).

From rodent studies, we know that MPLs can reduce the lipid accumulation in the liver, affect intestinal cholesterol absorption, modulate the postprandial lipid metabolism and protect rodents against colon carcinogenesis. Some of these benefits are either directly or indirectly related to improvements in intestinal barrier integrity, microtbial (re-)composition and inflammation. Other benefits, such as the anti-Alzheimer's effects scientists are still dabbling with (Pérez-Gálvez 2018), however, are probably immediate consequences of the incorporation (and stabilization) of absorbed MPLs in cells in the nervous system | Comment on Facebook!
References:
  • Blaženović, Ivana, et al. "Effects of Gut Bacteria Depletion and High‐Na+ and Low‐K+ Intake on Circulating Levels of Biogenic Amines." Molecular nutrition & food research (2018): 1801184.
  • Kwon, Ji‐Hye, et al. "Combination of Whole Grape Seed Flour and Newly Isolated Kefir Lactic Acid Bacteria Reduces High‐Fat‐Induced Hepatic Steatosis." Molecular nutrition & food research (2018): 1801040.
  • Malir, Frantisek, et al. "Ochratoxin A: 50 years of research." Toxins 8.7 (2016): 191.
  • Milard, Marine, et al. "Milk Polar Lipids in a High‐Fat Diet Can Prevent Body Weight Gain: Modulated Abundance of Gut Bacteria in Relation with Fecal Loss of Specific Fatty Acids." Molecular nutrition & food research (2019): 1801078.
  • Pérez-Gálvez, Antonio, et al. "Activities, bioavailability, and metabolism of lipids from structural membranes and oils: Promising research on mild cognitive impairment." Pharmacological research 134 (2018): 299-304.
  • Romo‐Vaquero, María, et al. "Deciphering the Human Gut Microbiome of Urolithin Metabotypes: Association with Enterotypes and Potential Cardiometabolic Health Implications." Molecular nutrition & food research (2018): 1800958.
  • Sueck, Franziska, et al. "Human Study on the Kinetics of 2′ R‐Ochratoxin A in the Blood of Coffee Drinkers." Molecular nutrition & food research (2018): 1801026.
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