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!
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.
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.
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.
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.
The fact that the gut microbiota plays an important role in digestion and metabolism should by now be common knowledge. There is now also abundant evidence that obesity is associated with a rarefied microbiome, the causes for which are not entirely clear.
One of the more adventurous approaches to rectifying this issue has been the idea of using fecal transplants from lean people in an attempt to ‘repoopulate’ (pardon the pun) the gut of people living with obesity.
In one such study by Valentin Mocanu and colleagues from the University of Alberta, in which I happened to be peripherally involved, now published in Nature Medicine, suggests that it may not be enough to just transplant the bugs, but that you also need to support them.
The double-blind study involved 70 volunteers with severe obesity and metabolic syndrome, who were randomised into two groups, one receiving fecal transplants from lean donors (in the form of capsules) vs. placebo capsules. Each of these groups were then further randomised to receive daily supplements of either high-fermentable (HF) or low-fermentable (LF) fiber over 6 weeks.
This treatment resulted in a significant improvement in HOMA as a measure of insulin resistance in the Fecal-Microbial-Transplant-Low-Fermentable fibre group (FMT-LF), with no changes in any of the other groups. In addition, there was also restoration of the physiologic patterns of GLP-1 secretion in the FMT-LF group.
As for the microbiome itself, the FMT-LF intervention was associated with increases in bacterial richness (Chao1 index) from baseline to week 6 with the FMT-LF intervention resulting in changes in seven genera and 12 amplicon sequence variants (ASVs), several of which were detectable at week 6, including increases in the relative amounts of Phascolarcobacterium, Christensenellaceae, Bacteroides and Akkermansia muciniphila and decreases in Dialister and Ruminococcus torques.
Most of these changes were no longer apparent after 12 weeks.
As for why these changes were only seen in the FMT-LF group, the authors have the following speculation to offer,
“Possible explanations include the ability of cellulose to act as a bulking and binding agent, which could alter metabolite luminal concentrations, influence gastrointestinal transit and modulate the donor microbe–host mucus layer interface. Cellulose supplementation may also directly alter the function of specific taxa, including cellulose-degrading H2-producing methanogens, leading to changes in gut microbial fermentation efficiency and by-products. Together these factors might constitute mechanisms through which the FMT-LF intervention increases microbial diversity and richness while also potentially inducing functional changes in taxa associated with host HOMA2-IR/IS improvements.”
Irrespective of the actual mechanisms, the study does suggest that daily low-fermentable fiber supplementation may be needed to support an FMT intervention to improve insulin sensitivity, and may perhaps act by differentially modulating engraftment of select bacterial taxa and the enteroendocrine axis.
Whether or not this approach will ever translate into a viable treatment for patients with metabolic syndrome remains to be seen.
Although there is now a solid body of evidence showing that exercise alone has a rather minimal effect on body weight, I have met countless people who swear by how exercise helped them lose weight. Indeed, ‘not enough exercise’ is one of the most common ‘excuses’ I’ve heard from my patients and ‘I need to exercise more’ is probably the most common solution that patients consider for losing weight.
And clearly, there are those patients, who have lost significant amounts of weight with exercise, which simply cannot be explained by the number of calories burnt (which is generally far less than most people think).
This led me, several years ago, to postulate the hypothesis that some people lose weight when they begin an exercise program because it reduces their appetite, thus resulting in lower caloric intake.
However, as much as I love this hypothesis, it seems that the overall effect of exercise on appetite and energy intake is pretty neutral, at least according to a meta-analysis by Kristine Beaulieu and colleagues published in Obesity Reviews.
The researchers reviewed 48 articles that reported the relationship between an exercise intervention and changes in caloric intake, appetite, hunger, satiety, and other features of ingestive behaviour.
Despite noting that the vast majority of these studies were sadly of rather poor quality, there did not appear to be any significant impact of exercise on caloric intake – in either direction!
While this finding is consistent with the fact that exercise very seldom leads to any significant change in body weight, it does pose the questions of a) why some people claim that exercise helped them lose vast amounts of weight, and perhaps b) why regular exercise is associated with a greater likelihood of keeping weight off.
As the authors discuss, there are several influences of exercise on ingestive behaviour that may need to be considered (and for which there is some evidence). These include an improvement in satiety quotient as well as potential reduction in overconsumption due to alterations in impulsivity, dietary restraint, food reward/preferences, as well as the notion that the increased energy flux induced by exercise could generate better control of eating behaviour.
However, these mechanisms appear to be, on average, rather minimal in that they may support individuals attempting to reduce their caloric intake but on their own are unlikely to do so.
Obviously, irrespective of any effects on appetite or body weight, the health benefits of regular exercise are indeed profound and manifold. This applies to people of all shapes and sizes. So please don’t get discouraged when your exercise routine does not move those numbers on the scale.
Like most doctors, German docs are not particularly knowledgeable about the rather complex biology and psycho-sociology of obesity. However, they do appreciate that obesity is an important health problem, very much relevant to their practice.
So how do they feel about it and, perhaps more importantly, what are they doing to address it?
This question was examined in a recent qualitative study by Julian Wangler and Michael Jansky from the University of Mainz, published in the European Journal of Clinical Practice.
For their study, the researchers conducted interviews with 36 German general practitioners about their attitudes, behaviours and strategies towards patients with obesity.
Based on their analysis of the interviews, four types of physicians were identified.
Type 1 were those they described as “The Resigned” – these were doctors who had essentially given up and placed the blame squarely on the shoulders of their patients. Interviewees in this group went as far as to emphasise that obesity was ‘not a disease like any other’, but rather due to character predisposition involving living to excess or the ‘urge to let themselves go’. They viewed interventions as largely futile, mainly because patients were unwilling to take responsibility. Years of frustration with these patients has led them to doubt whether general practitioners can manage this type of patient effectively. Instead, they see a role for specialists using drugs, psychotherapy or possibly surgery as the final option.
Type 2, called “The Instructors” were doctors who attributed obesity largely to a combination of life circumstances and predisposition, and viewed structured exercise and diet programmes for their patients as delivering the best results. These doctors were often connected to a network of exercise and dietary practitioners resources in the community to which they could refer their patients. However, rather than providing continuous patient consultation at close intervals, they encouraged a ‘focussed and concentrated jump-start’ to ‘set the scenes for consistent and gradual weight loss’ in an individually matched motivational exercise programme. This group of doctors appreciated the use of health apps but was vehemently opposed to the use of medications or surgery, due to the risk of ‘yo-yo effects’.
Type 3, called “The Motivators”, were likewise opposed to the use of medication or surgery, but did have a far more favourable view of people living with obesity than “The Resigned”. Not only did they recognise the importance of sensitive communication and a collaborative approach to the doctor–patient relationship, but also felt that it is essential to provide enough time for consultation and remain accessible, even with treatment setbacks. Interviewees in this group had sometimes undergone additional training in psychotherapy and psychoanalysis and believed that this knowledge played a valuable role in successful long-term obesity management.
Type 4, “The Educators” were a mix between Type 2 and Type 3, but placed their bets on the importance of prevention rather than treatment. Although they provide support and care, this group was far more sceptical as to the success of treating obesity once it was established. Rather, they saw it as best to intervene early and to take regular health check-ups as an early warning system very seriously. Some in this group had undergone further training in nutritional medicine. For this group, the issue of medication or surgery did even not come up.
Irrespective of their “Type”, there was a general sense that ‘successful obesity patient management was often time-consuming, requiring a high level of medical commitment with new attempts at treatment after previous attempts had failed.’ Furthermore, all interviewees decried the severe lack of supporting structures and care services for preventing obesity and managing treatment in primary care.
While this categorisation of primary care practitioners with regards to attitudes and approaches toward obesity management is very informative (if not unexpected), it should concern us that none of these groups appear convinced of the need for or the effectiveness of medications or surgery. Rather, they appear stuck in a world where behavioural or “lifestyle” approaches (with varying levels of motivational, educational, psychological,and community support) are still viewed as the most effective treatments for this chronic disease.
This not only reflects their individual professional and perhaps personal biases toward obesity and people living with obesity, but also highlights the fact that we still have a long way to go before medical treatments including medications and surgery become the accepted mainstay of obesity management, similar to other chronic diseases for which such treatments exist.