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Here’s Why You Need To Eat Your Sauerkraut!

In most cultures, fermented foods (yoghurt, kim-chi, sauerkraut, etc.) have long been a staple component of traditional diets. 

Now, according to Hannah Wastyk and colleagues from Stanford University, in a paper published in Cell, these foods may not just be a convenient method of preservation, but also an important modulator of immune function. 

The authors studied the effects of a diet containing high amounts of fibre (e.g. fruits, vegetables, legumes, grains, nuts and seeds) compared to a diet rich in fermented foods (e.g. yogurt, kefir, fermented cottage cheese, fermented vegetables, vegetable brine drinks, kombucha, etc.) on the microbiome and immune status of healthy volunteers. 

Over the 10-week randomised dietary intervention, the high-fibre diet increased levels of microbiome-encoded glycan-degrading carbohydrate active enzymes (CAZymes) without altering the intestinal flora, whereas the high-fermented-food diet incrementally increased microbiota diversity while decreasing inflammatory markers. 

As the authors discuss,

Given that fermented foods have historically been part of many diets around the world, consuming fermented foods may offer an effective way to reintroduce evolutionarily important interactions. They may also provide compensatory exposure to safe environmental and foodborne microbes that have been lost over the course of sanitizing the industrialized environment.

Thus, Fermented foods may be valuable in countering the decreased microbiome diversity and increased inflammation pervasive in industrialized society.

Although not examined in this study, in my personal experience sauerkraut goes well with another fermented German staple, i.e. Beer! Don’t tell me that’s just a co-incidence!

Prost!

@DrSharma
Berlin, D

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Can Gastrointestinal Effects Alter Mental Health After Bariatric Surgery?

Although the overall impact of bariatric surgery on mental health is overwhelmingly positive, there remains a subset of individuals in whom mental health issues like self-harm or addictions may appear after surgery. 

Now a paper by Robyn Brown and colleagues, published in Nature Reviews Endocrinology, presents an intriguing hypothesis, that alterations in the gut-axis may play a role in these problems. 

As readers are well aware, bariatric surgery (with some variations depending on the type of procedure) results in profound changes in gut function including alterations in incretin release, intestinal flora, bile acid disposition, and vagal signaling.

As discussed in the paper, all of these factors may potentially affect mental health. However, the evidence is sparse and often contradictory. As the authors point out, despite a strong potential for some of these alterations induced by surgery to alter mental health, few mechanistic studies appear in the animal or clinical literature that could potentially lead to better mechanistic insights and hopefully effective preventive and treatment measures.  

Be the role of the gut in adverse mental health outcomes after bariatric surgery as it may, it’s perhaps important to recall that there are plenty of other probable contributing factors to adverse mental health in bariatric patients. 

These include high rates of pre-existing depression, unmet expectations regarding the life-changing effects of weight loss, post-surgical alterations in the absorption of antidepressant and anxiolytic medications, and changes in alcohol metabolism, which might increase disinhibition and impulsivity, leading to self-harm. 

In addition weight regain and recurrence of weight-related comorbidities, body dissatisfaction (perhaps heightened by excess skin after weight loss), as well as the reduced capacity to eat or enjoy highly-palatable foods as an emotional coping strategy may play a role in individual patients.

Thus, although fear of mental health issues post surgery should probably not deter anyone from undergoing surgery if they really need it, clinicians should be aware of the possibility of adverse mental health outcomes and counsel and monitor patients accordingly. 

DrSharma,
Berlin, D

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How Common Are Monogenic Forms of Obesity And What Can We Do About Them?

Most of obesity is clearly polygenic, meaning that many (perhaps hundreds) of gene variants may cumulatively or synergistically increase genetic predisposition in a given individual. In contrast, monogenic forms of obesity, where a single gene variant (e.g. loss-of-function leptin deficiency) may have a profound effect on body mass, are thought to be exceedingly rare. 

However, a recent paper by Kaitlin H Wade, published in Nature Medicine, suggests that some monogenic forms of obesity may be a lot more frequent than we think. 

In this study, the researchers examined the MC4R coding sequence in 5,724 participants from the Avon Longitudinal Study of Parents and Children and found that heterozygous loss-of-function (LoF) mutations in MC4R affected around 1 in 337 (0.3%) individuals with profound effects on body weight. 

At age 18 years, carriers of LoF mutations were almost 18 kg heavier with a BMI almost 5 points higher than non-carriers. 

Extrapolating this to a country like Germany with almost 20 million people living with obesity, LoF mutations in the MC4R gene could be the key culprit in almost 6,000 individuals. Clearly, genetic screening for both children and adults who experience significant weight gain in early childhood appears prudent to identify such individuals.

For them, the good news is not only that they can stop blaming themselves for their excess weight, but also that there may be promising treatments on the horizon. 

Thus, the MC4R-agonist setmalonitide, recently approved by the FDA for treatment of derangements of the melanocortin pathway caused by pro-opiomelanocortin (POMC) deficiency, proprotein subtilisin/kexin type 1 (PCSK1) deficiency, or leptin receptor (LEPR) deficiency, may turn out to also be effective in people with MC4R mutations. 

This may be attributable to the fact that setmelanotide appears to be significantly more potent at the MC4R than the endogenous ligand alpha-melanocyte stimulating hormone (α-MSH) and (at least in vitro) can disproportionally rescue signaling by a subset of severely impaired MC4R mutants. 

Specific clinical trials with setmelanotide in individuals with MC4R mutations are currently underway. 

DrSharma
Berlin, D

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Does Elevated BMI Justify Denial of Knee-Replacement Surgery?

A substantial number of  people living with obesity in need of knee-replacement surgery will have either been flatly denied surgery, or told to lose weight prior to qualifying for surgery. This common practice is largely based on the notion that outcomes in people with elevated BMI are generally poor, operations are riskier, and the life of the prosthesis due to loosening or wear may be drastically shortened. 

But, is this really the case?

Not, according to a large observational cohort study by Jonathan Thomas Evans and colleagues, just published in PLOS.

The researchers examined data from over 490,000 total knee replacements collected in the National Joint Registry (NJR) for England, Wales, Northern Ireland, and the Isle of Man from 2005 to 2016.

While individuals with higher BMI were slightly more likely to undergo revision surgery within 10 years of receiving their prosthesis, revision rates in all BMI classes remained well withing the accepted 10-year benchmark of 5%. 

Moreover, all BMI categories saw important improvements in function scores, which were only marginally (below the minimal detectable change) compared to patients with “normal” BMI.

Finally, there was no indication of increased mortality risk in higher BMI patients. In fact, 90-day mortality rates were significantly lower in patients with overweight and class I obesity than  in those with “normal” BMI. 

Thus, the authors suggest that policies limiting access to knee-replacement surgery based on BMI may no longer be justifiable. 

On the other hand, it may be important to note that this cohort most certainly represents a substantial selection bias with surgeons perhaps selecting fitter patients with raised BMI for surgery (“healthy-patient effect”). 

Or, as the authors put it,

“It appears that even if some patients with raised BMI are at risk of poorer outcomes, the outcomes remain acceptable by contemporary standards, and the selection process of orthopaedic surgeons is effective at identifying the correct patients to operate on at a population level.

Be that as it may, I would probably predict that if a staging system like the Edmonton Obesity Staging System (EOSS) were to be applied to this cohort, any residual effect of BMI will likely disappear – I would expect outcomes to be poorer the higher the EOSS stage, irrespective of BMI. 

For now, these data can certainly be used to initiate discussions on official or unofficial policies that restrict access to knee replacements based on BMI.

@DrSharma,
Berlin, D

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Do Probiotics Have More Going For Them Than Just a Good Story?

Recognition of the important role of the gut microbiome in digestion and metabolism (and possibly the neuroendocrine pathways involved in regulating ingestive behaviour) have spawned a whole industry of probiotics, enthusiastically marketed with often hyperbolic health claims.

How good a use is this of anyone’s money?

Not much, according to a meta-analysis by Amir Hadi and colleagues, just published in Clinical Nutrition

The researchers summarized data from nine randomised controlled trials that examined the effect of pro-/synbiotics on a wide range of metabolic parameters. Six used probiotics and three used synbiotics (formulated combinations of pre- and probiotics) in their intervention arm.

The studies were rather small (only 344 participants (176, intervention group; 168, control group) were included in the meta-analysis) and notably of short duration (between three weeks and seven months).

Overall, there was no discernible effect on body weight, BMI, waist circumference, fasting glucose, fasting insulin, HOMA index, TG, LDL-C, HDL-C, with only a minor difference in total cholesterol levels in studies of longer duration.

To be fair, there was some heterogeneity in outcomes based on the number of probiotic strains, the intervention duration, and participants’ characteristics, however, even the greatest effects seen in individual studies, were nothing to write home about. 

At this time, the consumption of pro-/syn-biotics to improve metabolism appears to be based more on hope (and a good story) than on any notable evidence.

@DrSharma
Berlin, D

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