A link between the gut microbiota and obesity was first reported in 2006 by Jeffrey Gordon and his group at Washington University in St. Louis, who found that microbial populations in the gut are different between obese and lean people, and that when the obese people lost weight, their microflora reverted back to that observed in a lean person. This suggested that obesity has a microbial component (Nature, Vol. 444, pp. 1022-1023, 1027-1031).
A 2013 paper in Science (Vol. 341, Issue 6150), also led by Professor Gordon, found that transplanting gut bacteria from obese humans into germ-free mice leads to greater weight gain and fat accumulation than mice that were given bacteria from the guts of lean humans.
A recent rat study from scientists at the University of Georgia, Athens that transplanted the microbiota from lean donors and combined this with prebiotics (inulin) produced beneficial shifts in the microbiota even when the animals continued to consume a high fat (“Western”) diet.
This has led many research groups to explore if probiotics may help manage weight.
The online marketplace
The market has responded with some probiotic-based products touting metabolism and weight management claims, many of which were based on classic Lactobacillus and Bifidobacterium species and strains, but the approval of GLP-1 receptor agonist drugs by the U.S. Food and Drug Administration and the rapid establishment of GLP-1 in the consumer psyche has led to a boom in dietary supplement products making GLP-1 claims.
According to Ewa Hudson, director of insights at Lumina Intelligence, there are currently 75 supplement products making GLP-1 claims on Amazon USA, with 38 of those being biotic products.
These include probiotic-only, prebiotic-only and synbiotic products, and Akkermansia is leading the way in 76% of all the biotics products making GLP-1 claims.
The Akkermansia story is impressive given that A. muciniphila MucT was first isolated and described in 2004. According to a 2022 paper by Patrice Cani et al. published in Nature Reviews Gastroenterology & Hepatology, “… in less than 15 years, the beneficial effects of A. muciniphila MucT have been translated from preclinical observations to human intervention in the context of metabolic syndrome. This situation is unique and unparalleled by other next-generation microorganisms.”
A. muciniphila and GLP-1
Akkermansia muciniphila is a Gram-negative, anaerobic bacterium that colonizes the gut during the first year of life. The bug reportedly accounts for about 3% of the human gut microbiota, and its abundance in the intestinal mucus layer is inversely correlated with BMI, type 1 diabetes and bowel disease in humans.
Akkermansia is known to produce nutrients that feed intestinal cells responsible for producing the intestinal mucus layer, which helps to maintain healthy intestinal barrier function and controls gut permeability and low grade inflammation in the gut.
Korean scientists reported in 2021 that A. muciniphila may secrete a protein that stimulates a “modest increase of circulating GLP-1 just after an oral glucose challenge.”
Much of the research into the species has been conducted in Belgium and the Netherlands by scientists at the Catholic University of Louvain and Wageningen University, and a spin-off company called A-Mansia was launched several years ago to develop of A. muciniphila products. The A-Mansia company focuses on the pasteurized form of the bacterium.
On Amazon US, Pendulum is the leading brand with estimated sales of almost three-quarters of a million dollars on the platform. Products are formulated with live A. muciniphila, which the company claims can increase the natural production of GLP-1 hormone, but adds a disclaimer on its website that this is based on preclinical data.
Even among the prebiotic-only products making GLP-1 claims, there is also an indirect play for Akkermansia, because some prebiotics may increase levels of the bacterium. For example, SuperGut’s GLP-1 boosting prebiotic mix is formulated with a combination of resistant starches, including Solnul, which has been reported to boost Akkermansia levels and increase free fatty acids.
Next generation probiotics
Moving beyond Akkermansia, there is continued interest in other next generation probiotics (NGPs), although the data for many of these remains early phase.
“The advent of sophisticated molecular methods has revolutionized the study of NGPs as potential preventive and therapeutic anti-obesity agents,” wrote the authors of a recent review on role of next-generation probiotics in obesity in the International Journal of Molecular Sciences.
“Notably, there are numerous, mostly anaerobic bacteria that have been associated with weight loss. The study of NGPs has revealed a promising potential in the context of obesity, metabolic syndrome, NAFLD and T2DM. However, there is much to be conducted in this research field.”
NutraIngredients has been tracking some of the more exciting strains in this field, including Hafnia alvei HA4597, a strain being explored and developed commercially by French start-up TargEDys SA, which was acquired by French pharmaceutical company Biocodex in 2023.
As we reported in 2021, H. alvei HA4597 may promote satiety by producing the caseinolytic protease B (ClpB) protein, which has been reported to mimic the appetite-reducing alpha-melanocyte-stimulating hormone (alpha-MSH).
These effects are supported by findings from a 12-week supplementation trial in overweight adults, with the probiotic found to significantly increase the proportion of overweight subjects losing at least 3% and even 4% of baseline body weight while following a hypocaloric diet over 12 weeks. Such weight loss levels were described as clinically relevant by the researchers.
Other NGPs
We’ve also been tracking the R&D behind Dysosmobacter welbionis J115T, a novel bacterium from the human gut isolated by a team of researchers from the Catholic University of Louvain. The strain is found in up to 70% of the healthy population, and lower abundance is correlated with higher BMI, fasting glucose levels and higher HbA1c (glycated hemoglobin, a marker of long-term presence of excess glucose in the blood) in obese people.
The team, led by Professor Patrice Cani, first reported the discovery of D. welbionis J115T in 2020 in a paper published in the International Journal of Systematic and Evolutionary Microbiolog, and followed by a paper published in the journal Gut in 2021 that found that daily administration of live D. welbionis J115T could blunt the high-fat diet induced metabolic disorders in lab mice. The strain appeared to be acting on both white and brown adipose tissue metabolism.
Also noteworthy, scientists from Duksung Women’s University and Mediogen Co., Ltd, in Korea have report that mice fed a high fat diet and supplemented with Weissella cibaria MG5285 for eight weeks experienced significant improvements in a range of health measures, including benefits for body weight and liver health. (Food & Nutrition Research, doi: 10.29219/fnr.v65.8087).
Lactobacillus and Bifidobacterium
But it’s not all about the next gen probiotics, with studies supporting potential anti-obesity activity of a range of more traditional Lactobacillus and Bifidobacterium strains.
Definitions
A probiotic is defined as a “live microorganisms which when administered in adequate amounts confer a health benefit on the host” – FAO/WHO, 2002
A prebiotic is "a substrate that is selectively utilized by host microorganisms conferring a health benefit" – ISAPP, 2017
A synbiotic is "a mixture comprising live microorganisms and substrate(s) selectively utilized by host microorganisms that confers a health benefit on the host”– ISAPP 2020
A postbiotic is "preparation of inanimate microorganisms and/or their components that confers a health benefit on the host" – ISAPP 2021
For example, ADM’s Bifidobacterium animalis subsp. lactis BPL1 (CECT 8145) strain is supported by data from a three-month randomized, parallel, double-blind, placebo-controlled trial. The trial, published in the International Journal of Obesity, found that supplementation with either live or heat-killed (postbiotic) BPL1 led to significant reductions in waist circumference (-1.75 cm in the live and -1.84 cm heat-killed groups) and the live bacterium produced statistically significant reductions in BMI versus both its baseline levels and the placebo group.
The live (probiotic) form of BPL1 is used in Culturelle’s Metabolism + Weight Management product launched in the United States and Canada in 2021.
Japan’s Morinaga Milk Industry Co., Ltd also have a weight management strain: Bifidobacterium breve B-3. Data from a 12 week clinical trial with pre-obese adults found that the strain may slash body fat mass and percent body fat of 0.6 kg and 0.7%, respectively (Bioscience of Microbiota, Food and Health, doi: 10.12938/bmfh.18-001).
IFF’s Bifidobacterium animalis ssp. lactis 420 (Howaru Shape) in combination with Litesse Ultra prebiotic fiber has been reported to reduce body fat by 4.5%, trunk fat by 6.7% and waist circumference by one inch (2.6 cm), versus placebo (EBioMedicine, doi: 10.1016/j.ebiom.2016.10.036).
Healthy weight management is also an area of high interest to Novonesis. In addition to the potential benefits of BB-12, data from human clinical studies shows that the company’s Lactobacillus gasseri BNR17 strain may contribute to maintenance of a healthy weight, a healthy body mass index and support healthy levels of abdominal fat (Jung et al. Korean J Fam Med 2013, Kim et al. J Med Food 2018).
Also noteworthy, Austrian start-up Slimbiotics is exploring the potential of a combination of Lactobacillus strains originally isolated from African fermented food Kimere. The company’s plant-derived strain combination includes L. fermentum K7-Lb1, L. fermentum K8-Lb1, and L. fermentum K11-Lb3.
In the United States, Slimbiotics announced a partnership earlier this year with DSM i-Health to distribute its metabolic health probiotics in the North American and Chinese markets under the Culturelle and Estroven brands.
Future outlook
As the category evolves and the science deepens, one advance to keep an eye on will be the overlapping areas of study, including obesity, aging and the gut-brain axis.
“Many hallmarks are shared between obesity and aging, one of which is gut microbial dysbiosis,” wrote scientists from McGill University in a May 2024 review in Microbiome Research Reports.
“The gut microbiota may be targeted to re-establish a healthy flora in obese or aged individuals, thereby improving the disease phenotypes, underlying metabolic dysfunction and systemic comorbidities. Importantly, the unique relationship between obesity and aging may be targeted with the use of biotic therapies through the well-established GBA [gut-brain axis].
“The microbiome and various forms of biotics—namely prebiotics, probiotics, synbiotics and postbiotics—offer distinct benefits to the host, which can be exploited to develop novel therapeutics for obesity, aging and related diseases.”