Can probiotics manage metabolism, mood, and body mass?

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Nutritional OutlookNutritional Outlook Vol. 26 No. 8
Volume 26
Issue 8

If the gut-brain axis connects our microbiome and mood, mass, and metabolism, can probiotic supplementation support all three?

© Sdecoret - Stock.adobe.com

© Sdecoret - Stock.adobe.com

Remember back when probiotics went by the endearing shorthand “good gut bugs”? It wasn’t that long ago, and the vernacular actually fit, considering that the microbes first earned their fame mainly for colonizing the gut and improving conditions there.

But as science reminds us seemingly every time a new study drops, probiotics’ spheres of influence extend well beyond the digestive tract and its goings-on to envelop metabolic health, body mass—even mood.

In light of the toll these health factors take on society when they go south, understanding how probiotics might turn the tide is a matter of genuine urgency, argues Allie Chandler, head of brand and B2B marketing, Novozymes OneHealth North America (Franklinton, NC).

“The pressing nature of poor metabolic health, obesity, and stress is evident both in their prevalence and their economic impact,” she declares. “But addressing these issues isn’t just about reducing healthcare costs; it’s about enhancing quality of life for millions. That’s why leveraging breakthroughs in research, including probiotics’ potential benefits, is absolutely a step in the right direction.”

Taking a Toll

The direction that metabolic health, weight, and mental health have been taking “isn’t the same today as it was 50 years ago,” Chandler concedes. And as far as she’s concerned, “We’re at a disadvantage from the start in many ways.”

One such way is the extent to which contemporary culture spreads stress into every corner of our days. “Two-thirds of adults aged 18 to 54 report feeling stress,” Chandler notes, “which isn’t a trivial concern, as the ramifications are multifaceted” and include everything from disrupted sleep and fractured concentration to greater risk for anxiety and depression.

And as anyone familiar with “stress eating” knows, when day-to-day pressure meets easy access to highly palatable foods, comfort can look a lot like overindulgence—the results of which are manifest in current rates of overweight and obesity.

In fact, Jordi Riera, chief business officer, Kaneka Probiotics (Pasadena, TX), finds the rising rates of both conditions “alarming,” and points to World Health Organization data indicating a near tripling of their prevalence between 1975 and 2016, with 39% of adults aged 18 and older now qualifying as overweight and 13% meeting the definition of obese.1

Cluster of Concerns

The knock-on effects of all this extra weight only add to the burden of chronic concerns that, collectively, constitute what we call metabolic syndrome—a cluster of conditions comprising high blood pressure, poor blood-sugar control, excess abdominal fat, abnormal lipid levels, and more, the combined effects of which correlate to higher risks for cardiovascular disease and diabetes.

The associated costs sorely strain the healthcare system, too, with results of a 2009 study showing that subjects with metabolic syndrome incurred average annual healthcare expenses 1.6 times those of subjects without: $5,732 compared to $3,581.2

Yet as Steve Prescott, senior vice president, business development/operations, Synbiotic Health (Lincoln, NB), notes, the price of poor metabolic health isn’t denominated in dollars and cents alone, but also in “the difficulties encountered on a daily basis by people affected,” he says, “whether that’s more health appointments and hospital visits or the inability to do activities they enjoy.”

In the Loop

Chipping away at these costs is complicated by the fact that the elements contributing to metabolic disorders—including high body mass and stress—exist in a vicious circle that’s…well, complicated.

As Margherita Patrucco, technical marketing and product development, Probiotical SpA (Novara, Italy), explains, “Excess weight, especially obesity, harms metabolic health by disrupting hormonal regulation and appetite control—thus causing insulin resistance, dyslipidemia, high blood pressure, and inflammation.”

Meanwhile, overweight and obesity can generate stress that in its own right compromises metabolic health by promoting further unhealthy eating, discouraging physical activity, and curtailing high-quality sleep.

The upshot: We wind up in “an insidious feedback loop where stress, weight gain, and poor metabolic health reinforce each other,” Patrucco concludes, “making the cycle challenging to break.”

Axis Powers

But a potential point of leverage lies in one of the chain’s key links: the gut microbiota.

As Riera points out, metabolic health “encompasses an intricate interplay of genetic, epigenetic, dietary, and lifestyle factors, as well as microbiome-related factors. Growing evidence indicates that this ‘metabolic dance’ involves a symbiosis between our bodies and the ecosystem of microorganisms that comprise our microbiome.”

The choreographers of that dance are the various “gut-organ axes” that coordinate communication between gut microbes and our bodies’ governing systems—and an axis that’s attracting significant attention for its influence on whole-body health is the gut-brain axis connecting mood, mass, metabolism, and our microbiome in a bidirectional conversation.

Target Practice: Matching Strain to Symptoms

Getting probiotic supplementation right is all about targeting the strain to the concern—whether that’s gut health and immunity or metabolic health, mood, and weight management.

And as Allie Chandler, head of brand and head of B2B marketing, Novozymes OneHealth North America (Franklinton, NC), says, “Within the context of the gut microbiome, there are keystone species that play crucial roles in maintaining the structure and function of the microbial community and that can have profound impacts on host physiology—including on weight and metabolic health.”

Here are some of her top picks, and why:

Akkermansia muciniphila
Feeds on the mucin layer of the gut, which can stimulate the production of new mucin, maintaining a healthy gut barrier.

Metabolic health
Higher levels of A. muciniphila have been associated with improved glucose homeostasis and reduced adipose tissue inflammation (lower levels associated with obesity and type 2 diabetes).

Faecalibacterium prausnitzii
It’s a major butyrate producer, which is a short-chain fatty acid that serves as an energy source for gut cells and has anti-inflammatory properties.

Metabolic health
Lower levels of F. prausnitzii have been linked to conditions like inflammatory bowel disease, obesity, and type 2 diabetes.

Bacteroides thetaiotaomicron
This bacterium is involved in carbohydrate fermentation and the production of short-chain fatty acids.

Metabolic health
Through its activity, it helps maintain gut barrier function, modulates immune responses, and impacts energy extraction from the diet.

Inflammatory Statements

The back-and-forth dynamics of this biome-based relationship are complicated in practice but elegant in theory: In short, when our microbial ecosystem is balanced, our moods, metabolic function, and body mass are more likely to maintain their own healthy balance. But when something—say poor diet or stress—tips the microbiome out of whack, “dysbioses” result, with inflammation being a characteristic result.

Consider what happens if a disturbance prevents the gut microbiome from maintaining a strong gut barrier—one of its core functions, Prescott notes. “When these microbes fail to do that job, the barrier can become permeable and allow bacterial components or other substances to leak through, causing systemic inflammation as the immune system reacts to these unwelcome substances in the bloodstream,” he says.

This state of “endotoxemia,” he goes on, underlies the development of obesity and metabolic problems like diabetes, and can even get fuel for its fire from stress, “as the body’s stress-response system, the hypothalamic-pituitary-adrenal axis, links the stress we feel to physiological effects,” he notes.

What’s more, adds Caroline Montelius, department manager, global scientific affairs, Probi (Lund, Sweden), a common denominator linking healthy individuals with garden-variety moderate-to-high stress with those experiencing diagnosed depression and anxiety is the presence of inflammation—which, she emphasizes, “ties back to the gut, as the gut harbors a large proportion of inflammatory cytokine-producing immune cells.”

Probiotic Pivot

No wonder studies correlate the lower microbial diversity that typifies industrialized populations with higher incidences of metabolic disorders, says Camille Binachon, product manager, Lallemand Health Solutions (Mirabel, Canada).

“Differences in gut composition due to lifestyle and diet can contribute to obesity, cardiovascular diseases, type 2 diabetes, and nonalcoholic fatty liver disease,” she notes—all of which are conditions she describes as “intrinsically linked, as about 60%–70% of obese patients are dyslipidemic, and individuals with type 2 diabetes have a twofold increased risk for cardiovascular disease.”

Those statistics paint an ominous picture. But if an imbalanced microbiome sets us up for a host of ills, might interventions aimed at bringing it back into order—as through probiotic supplementation—bend the curve? Montelius thinks they could.

“Reestablishing a balanced gut microbiota by adding clinically documented probiotic solutions has been shown to modulate the release of inflammatory cytokines, improving both brain function and metabolic health,” she says. And that’s just the start.

Prescott actually wagers that probiotics “might get at the root cause of obesity.” Among the strains that Synbiotic Health has studied and cultivated, “We know that Bifidobacterium adolescentis iVS-1 helps strengthen the gut barrier,” he says, “and because the gut barrier is implicated in obesity as mentioned above, this function could lay the groundwork for powerful effects on weight control via the gut.”

Even more-recent research into the strain’s actions indicates that it releases gamma-aminobutyric acid (GABA), too, he adds, “which helps regulate a number of important gut functions and, through the gut-brain axis, may have inhibitory effects in the brain, potentially resulting in stress reduction and sleep enhancement.”

Lipids and the Liver

“When it comes to lipid metabolism,” Riera adds, “a combination of three Lactobacillus plantarum strains—KABP-011 (CECT 7527), KABP-012 (CECT 7528), and KABP-013 (CECT 7529)—was found to reduce low-density lipoprotein, or LDL, cholesterol and triglyceride levels in blood.”3

The mode of action, he proposes, stems from the gut microbiota’s ability to regulate lipid metabolism and encourage cholesterol excretion via its influence on several metabolites, “including bile salts that display bile-salt hydrolase activity.”

More specifically, he explains, the liver synthesizes bile salts from blood cholesterol and then releases those salts into the intestine, where they facilitate fat absorption. Then those bile salts pass back into circulation through intestinal receptor sites and return to the liver for reuse in further bile-salt production.

Meanwhile, Riera continues, “After being converted to bile acids in the liver, only a small percentage of LDL cholesterol is typically eliminated from the body naturally.” Supplementation with the aforementioned combination of strains—which AB-Biotics formulated as its Floradapt Cardio/AB-Life probiotic but which is now sold under the Kaneka brand—appears to de-conjugate bile salts in the liver, preventing cholesterol’s reabsorption and increasing excretion. In other words, Riera says, “The liver has to absorb more blood cholesterol to synthesize de novo bile salts.”

All-in-One Action

Binachon notes that when Lallemand began exploring probiotic strains to address the triumvirate of body mass, mood, and metabolism, Lacticaseibacillus rhamnosus HA-114 caught the company’s eye thanks to studies showing that it not only reduced fat accumulation in an in vivo model of Caenorhabditis elegans, but that it also appeared to reverse neurodegeneration in animal models of amyotrophic lateral sclerosis (ALS) and Huntington’s disease through its ability to modify lipid metabolism.

So a recent double-blind, placebo-controlled clinical trial4 put the strain to the test in 152 overweight, otherwise healthy, adult humans participating in a personalized 500-calorie daily-deficit diet.

The researchers randomized subjects to take either 10 billion CFU/day of L. rhamnosus HA-114 or a placebo and measured physiological and psychological parameters as well as eating behavior using validated questionnaires at baseline and 12 weeks into the study.

The results showed that while both groups saw significant changes in body-mass index, waist circumference, fat mass, and body mass percentage—with no significant differences between groups—“beneficial changes in eating behaviors were observed in the probiotic group,” Binachon points out, “with participants reporting better self-control over hunger and binge-eating, and thus reduced food cravings.”

Moreover, the probiotic group reported that feelings of stress, anxiety, and depression “improved significantly following their diet,” Binachon continues. So by “restoring the balance of eating behaviors through the gut-brain axis,” she postulates, the probiotic “could also facilitate diet compliance.”

Finally, results showed that the strain significantly influenced fasting plasma insulin, homeostatic model assessment of insulin resistance (HOMA-IR), and LDL-cholesterol and triglyceride levels during the study, “highlighting the beneficial effects of probiotic interventions on eating behaviors, mental health, and metabolic profile,” Binachon says, “and reinforcing the validity of the gut-brain axis.”

Making a Dent

Such results rightly generate excitement—both among industry insiders and consumers…er, hungry for solutions.

But prudent observers of this space counsel caution. Kristin Kirkpatrick, MS, RD, LD, a registered dietician and Jetson (Chicago) partner, is one of them.

“Good health depends on many factors,” she says, “including genetics, sleep quality, diet, stress management, environment, physical fitness, and regular adherence to medical care—so there’s no one-size-fits-all approach. However, with the right clinically validated and non-generic strains, probiotics can have a great impact on our overall health when paired with diet and exercise.”

References

  1. World Health Organization. Obesity and Overweight. Updated June 9, 2021. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight
  2. Boudreau, D.M.; Malone, D.C.; Raebel, M.A.; et al. Health care utilization and costs by metabolic syndrome risk factors. Metab Syndr Relat Disord. 2009, 7 (4), 305-314. DOI: 10.1089/met.2008.0070
  3. Bosch, M.; Fuentes, M.C.; Audivert, S.; Bonachera, M.A.; Sara Peiró, S.; Cuñé, J. Lactobacillus plantarum CECT 7527, 7528 and 7529: probiotic candidates to reduce cholesterol levels. J Sci Food Agric. 2014, 94 (4), 803-809. DOI: 10.1002/jsfa.6467
  4. Choi, B.S.Y.; Brunelle, L.; Pilon, G.; et al. Lacticaseibacillus rhamnosus HA-114 improves eating behaviors and mood-related factors in adults with overweight during weight loss: a randomized controlled trial. Nutr Neurosci. 2023, 26 (7), 667-679. DOI: 10.1080/1028415X.2022.2081288
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