MUFAs And Longevity

Here is a paper from several years ago showing a link between mono-unsaturated fatty acids (MUFAs) and longevity in the worm Caenorhabditis elegans.  A molecular mechanism is given - worms deficient in a particular enzyme that modifies DNA and hence affects gene expression exhibit accumulation of MUFas and a longer lifespan. Dietary MUFAs were shown be able to enhance lifespan.  Perhaps this applies to mammals, including humans? Abstract:

Chromatin and metabolic states both influence lifespan, but how they interact in lifespan regulation is largely unknown. The COMPASS chromatin complex, which trimethylates lysine 4 on histone H3 (H3K4me3), regulates lifespan in Caenorhabditis elegans. However, the mechanism by which H3K4me3 modifiers affect longevity, and whether this mechanism involves metabolic changes, remain unclear. Here we show that a deficiency in H3K4me3 methyltransferase, which extends lifespan, promotes fat accumulation in worms with a specific enrichment of mono-unsaturated fatty acids (MUFAs). This fat metabolism switch in H3K4me3 methyltransferase-deficient worms is mediated at least in part by the downregulation of germline targets, including S6 kinase, and by the activation of an intestinal transcriptional network that upregulates delta-9 fatty acid desaturases. Notably, the accumulation of MUFAs is necessary for the lifespan extension of H3K4me3 methyltransferase-deficient worms, and dietary MUFAs are sufficient to extend lifespan. Given the conservation of lipid metabolism, dietary or endogenous MUFAs could extend lifespan and healthspan in other species, including mammals.

What We Eat Is What We Think?

Consider that diet can affect your gut microbiome.  Consider also that gut bacteria produce short chain fatty acids from dietary fiber, so that diet can not only affect what bacterial species are in the gut but what products they produce.  Now, take a look at this article on the “gut-brain axis” mediated in part by lipids, including fatty acids, and this other article on a similar topic.

“We are what we eat,” indeed.  Perhaps, we “think what we eat” as well.

Negative Effects Of Dietary Fiber Deficiency

Another role for dietary fiber shown here, abstract:

Despite the accepted health benefits of consuming dietary fiber, little is known about the mechanisms by which fiber deprivation impacts the gut microbiota and alters disease risk. Using a gnotobiotic mouse model, in which animals were colonized with a synthetic human gut microbiota composed of fully sequenced commensal bacteria, we elucidated the functional interactions between dietary fiber, the gut microbiota, and the colonic mucus barrier, which serves as a primary defense against enteric pathogens. We show that during chronic or intermittent dietary fiber deficiency, the gut microbiota resorts to host-secreted mucus glycoproteins as a nutrient source, leading to erosion of the colonic mucus barrier. Dietary fiber deprivation, together with a fiber-deprived, mucus-eroding microbiota, promotes greater epithelial access and lethal colitis by the mucosal pathogen, Citrobacter rodentium. Our work reveals intricate pathways linking diet, the gut microbiome, and intestinal barrier dysfunction, which could be exploited to improve health using dietary therapeutics.

Dietary fiber can have many beneficial effects, including the production of short chain fatty acids that are good for colonic health and of course fiber helps with bowel movements to avoid constipation.  This mouse study shows that when there is a deficiency of dietary fiber, the gut microbiota that would normally digest fiber will instead start using the gut mucus as an energy source, eroding the protective lining on the colon and allowing pathogenic organisms to have access.

Eat your fiber!

Short Chain Fatty Acids And Weight Loss

Can short chain fatty acids contribute to weight loss?  A paper looks at this, abstract:

Elucidating the mechanisms by which short chain fatty acids (SCFA) reduce body weight may assist in the development of an effective weight control strategy. Dietary supplementation of acetate, propionate, butyrate or their admixture was shown to significantly inhibit the body weight gain induced by high-fat diet feeding. Supplementation of SCFAs caused significant changes in the expressions of G-protein coupled receptor 43 (GPR43) and GPR41 characterized by increases in the adipose tissue and reductions in the colon. Additionally, they influenced the bacterial community structure in feces, with a reduction in the proportion of Firmicutes and an increase in the proportion of Bacteroidetes. The effects of dietary SCFAs on the GPR expression and gut microbiota composition may further result in body weight reduction by enhancing triglyceride hydrolysis and FFA oxidation in the adipose tissue, promoting beige adipogenesis and mitochondrial biogenesis, and inhibiting chronic inflammation.

Keep in mind that short chain fatty acids can be produced in the colon by the fermentation of dietary fiber by the gut microbiota, with beneficial effects for colonic health.  However, the effects described in this paper required direct supplementation of these agents into the diet of the test mice.  Nevertheless, the findings suggest a role for short chain fatty acids in weight control.

Fiber And Microbiota

Dietary fiber can increase levels of certain gut microbiota bacterial species, as well as higher levels of butyrate, a short chain fatty acid with beneficial anti-cancer effects in the colon.  Abstract:

BACKGROUND:

Dysfunction of the gut microbiota is frequently reported as a manifestation of chronic diseases, and therefore presents as a modifiable risk factor in their development. Diet is a major regulator of the gut microbiota and certain types of dietary fiber may modify bacterial numbers and metabolism, including short-chain fatty acid (SCFA) generation.

OBJECTIVE:

A systematic review and meta-analysis were undertaken to assess the effect of dietary fiber interventions on gut microbiota composition in healthy adults.

DESIGN:

A systematic search was conducted across MEDLINE, EMBASE, CENTRAL, and CINAHL for randomized controlled trials using culture and/or molecular microbiological techniques evaluating the effect of fiber intervention on gut microbiota composition in healthy adults. Meta-analyses via a random-effects model were performed on alpha diversity, prespecified bacterial abundances including Bifidobacterium and Lactobacillus spp., and fecal SCFA concentrations comparing dietary fiber interventions with placebo/low-fiber comparators.

RESULTS:

A total of 64 studies involving 2099 participants were included. Dietary fiber intervention resulted in higher abundance of Bifidobacterium spp. [standardized mean difference (SMD) 0.64 (95% CI: 0.42, 0.86); P < 0.00001)] and Lactobacillus spp. [SMD: 0.22 (0.03, 0.41), P = 0.02] as well as fecal butyrate concentration [SMD: 0.24 (0.00, 0.47), P = 0.05] compared with placebo/low-fiber comparators. Subgroup analysis revealed that fructans and galacto-oligosaccharides led to significantly greater abundance of both Bifidobacterium spp. and Lactobacillus spp. compared with comparators (P < 0.00001 and P = 0.002, respectively). No differences in effect were found between fiber intervention and comparators for α-diversity, abundances of other prespecified bacteria, or other SCFA concentrations.

CONCLUSIONS:

Dietary fiber intervention, particularly involving fructans and galacto-oligosaccharides, leads to higher fecal abundance of Bifidobacterium and Lactobacillus spp. but does not affect α-diversity. Further research is required to better understand the role of individual fiber types on the growth of microbes and the overall gut microbial community. This review was registered at PROSPERO as CRD42016053101.

Fasting And Stem Cell Function

In mice, a 24 hour fast improves the function of intestinal stem cells through effects on fatty acid oxidation (FAO).  Genetic knockout experiments emphasize the importance of FAO in the fasting effects and suggest possibilities for boosting intestinal stem cell regeneration.  Abstract:

Diet has a profound effect on tissue regeneration in diverse organisms, and low caloric states such as intermittent fasting have beneficial effects on organismal health and age-associated loss of tissue function. The role of adult stem and progenitor cells in responding to short-term fasting and whether such responses improve regeneration are not well studied. Here we show that a 24 hr fast augments intestinal stem cell (ISC) function in young and aged mice by inducing a fatty acid oxidation (FAO) program and that pharmacological activation of this program mimics many effects of fasting. Acute genetic disruption of Cpt1a, the rate-limiting enzyme in FAO, abrogates ISC-enhancing effects of fasting, but long-term Cpt1a deletion decreases ISC numbers and function, implicating a role for FAO in ISC maintenance. These findings highlight a role for FAO in mediating pro-regenerative effects of fasting in intestinal biology, and they may represent a viable strategy for enhancing intestinal regeneration.

More Against Red And Processed Meat

By 4028mdk09 - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=25399566

Is enhanced mortality associated more with red meat/processed meat consumption or with saturated fatty acid (SFA) consumption?  Is it the meat or the saturated fats?  A recent study says meat:

Among highly educated persons, aged >45 years, a high consumption of red, total, and red + processed meat was related to increased all-cause mortality, compared with those with low consumption, whereas no significant associations were found for SFA intake. Dietary guidelines should specifically limit meat consumption and not relying only in limiting SFA intake.

And:

…replacing 100 g of vegetables, fruits & nuts or cereals by 100 g of red meat resulted in higher mortality risk.

For older individuals eating more meat, there was some effect of more SFA consumption:

In these participants, SFA intake was non-significantly associated with mortality. However, isocaloric replacement of monounsaturated fat or carbohydrates by SFA resulted in significantly higher mortality risk. 

But overall this particular study provides data pointing the finger at red meat/processed meat.  Given the consistency of this finding with that of previous studies, it looks for now that excessive consumption of red meat/processed meat is a major dietary health risk.  Looking at all studies, SFA risk is more equivocal; this study does not show, overall, a significant risk, but other studies have showed such a risk.

Limiting red meat/processed meat consumption would seem to be a prudent dietary priority.  Limiting SFA may be a good idea as well, depending upon context and whatever other dietary recommendations a person has from their physician, etc., but the meat situation would seem more important at this point.  Who knows what further studies will say about SFA.