Let me introduce myself. My name is Mark Sisson. I’m 63 years young. I live and work in Malibu, California. In a past life I was a professional marathoner and triathlete. Now my life goal is to help 100 million people get healthy. I started this blog in 2006 to empower people to take full responsibility for their own health and enjoyment of life by investigating, discussing, and critically rethinking everything we’ve assumed to be true about health and wellness...Tell Me More
We know how important gut health is for overall health. We understand that it improves digestion, that our pursuit of extreme sterility has compromised our immune systems, and that the gut biome is etiologically involved in the pathogenesis of various health and disease states. We’re even familiar with the more esoteric functions of gut bacteria, like converting antinutrients into biovailable nutrients, synthesizing sex hormones and neurotransmitters, and mitigating the allergenicity of gluten. But what about gaining and losing body fat, the real reason most people get interested in diet in the first place—are the bacteria in your gut responsible for the fat on it?
The animal literature shows that direct manipulation of the gut biome can affect bodyweight and resistance to obesity. In one paper, transplanting gut bacteria from obese mice into lean mice led to a 60% increase in body fat and a rapid, 14-day descent into insulin resistance following the gut flora alteration. Another found that mice seeded with bacteria from lean mice even appear resistant to developing obesity when consuming fecal matter (a basic, if disgusting form of fecal transplant) from obese mice. At least in mice, “obese gut bacteria” and “lean gut bacteria” are well-established and appear to be causally-related to body weight.
In humans, the evidence is more mixed. Some studies find a higher proportion of Firmicute bacteria and fewer bacteria from the Bacteroidete family in the obese and overweight, while others find the opposite. The only concrete conclusion from a 2012 meta-analysis was that obesity in humans tends to track with an increase in members of the Firmicutes phylum. As for direct interventions, changes to the gut bacteria certainly accompany weight gain, but it’s unclear whether the relationship is coincidental or causal—and if causal, in which direction causality flows. Does obesity change the composition of the gut bacteria? If so, targeting the gut bacteria with diet, probiotics, prebiotics, and other therapies may not have the intended effect.
Indeed, a recent review suggested “that in humans the changes in gut microbiota are an association with rather than the cause of obesity.”
Rather than take their word for it, Let’s examine whether anything mediated by gut bacteria also changes body weight.
Antibiotics are the first place to look, because alteration of the gut bacteria isn’t a side effect of antibiotics. It’s a feature. The broad-spectrum antibiotics do the most collateral damage, killing good and bad bacteria alike. And there’s good evidence that antibiotics play a role in the development of obesity. For one, farmers have been giving low doses of antibiotics to their livestock to increase weight gain for decades; if it didn’t work, they wouldn’t spend the money on the drugs. In children, antibiotics increase the risk of obesity later in life in a dose-response manner. The more doses they receive, the more obese they get. The earlier they take them, the worse, with “antibiotic exposure before 6 months of age, or repeatedly during infancy, [being] associated with increased body mass in healthy children.” The effect may be strongest in boys.
Although the animal literature confirms that fecal transplantation from an obese rodent to a lean rodent can make the recipient gain weight (and vice versa), only one such example—a case study— exists in humans. A woman with a digestive disorder got a fecal transplant from her overweight daughter. It cured the disorder but the woman soon became obese, too.
Another human study gave 18 obese Dutch men with metabolic syndrome fecal transplants from lean donors. They did not lose weight, but they did experience improved insulin sensitivity and triglyceride numbers. These improvements reverted after about 12 weeks, probably because they maintained the diet that got them obese in the first place.
Can probiotics, which alter the composition of our gut bacteria, directly affect body weight? That’s the real question.
Earlier this year, an RCT found that giving overweight subjects two daily doses of L. curvatus HY7601 and L. plantarum KY1032 reduced body fat and waist circumference without affecting food intake or increasing exercise. It doesn’t look like body weight decreased, but that’s good news; it means fat was lost and lean mass retained or even increased. As a nice benefit, the probiotic group also experienced lower levels of oxidized LDL and saw their LDL particle size increase. L. plantarum is one of the strains I include in Primal Probiotics (formerly known as Primal Flora).
In aging mice, an L. reuteri probiotic increased testosterone levels. Particularly in men, restoring lagging testosterone levels can have huge benefits for body composition by increasing muscle mass and reducing body fat. However, increased testicular size may increase body weight.
Some researchers propose limiting probiotics in obese people to avoid weight gain via increased bacterial biomass, which most estimates say can weigh between 2 to 6 pounds. That’s like worrying about weight gain from increased muscle hypertrophy and bone mineral density. It’s also a valid confounder for weight loss in prebiotic and probiotic studies. If a person nurtures their gut and gains four pounds of bacterial biomass, that will show up on the scale and could, unless you’re measuring waist circumference or body fat percentage, throw off the measurement of effect.
LPS is a bacterial endotoxin produced when gram-negative bacteria die off in the gut. It’s implicated in leaky gut and, at least in animal studies, can exacerbate or even initiate obesity by increasing systemic inflammation and insulin resistance.
How can your gut biome affect the amount of LPS you produce—or admit to systemic circulation?
First, beneficial gut bacteria take up space along the gut wall, effectively forming a barrier to entry by pathogens. A healthier and more robust gut biome means there’s less room for LPS to slip through the tight junctions into wider circulation.
Second, a healthy gut biome produces less LPS. Certain probiotics, like B. infantis, may reduce LPS levels.
Third, providing enough fermentable fiber for your gut bacteria to eat means they’re less likely to consume the mucin protecting the gut lining from invasion. If you starve your gut bacteria, they will begin eating the mucosal barrier and open you up to LPS toxicity.
A common refrain you often hear is that “high-fat diets induce LPS toxicity.” And yeah, looking at most of the available literature, that appears to be true. Lipopolysaccharide rides along and absorbs better with fat. It’s right there in the prefix: “lipo.”
But a recent paper found that when you give mice whole foods-based diets rather than refined diets, the fat content has no bearing on LPS toxicity. If anything, increased dietary fat through whole foods increased mucin production and reduced LPS toxicity.
Several studies have wondered if changing the diet to include more fermentable fiber and shape the gut biome can reduce obesity, but there’s a problem with this approach: changing the diet changes the diet. There’s really no way to know if the change to gut bacteria is responsible for the change in bodyweight or if the diet is changing the bodyweight which changes the gut bacteria. You can’t easily disentangle the two.
In a recent paper, hospitalized obese kids were placed on a diet rich in fermentable fiber. Significant reductions in body weight were accompanied by concomitant alterations to the gut bacteria. Transplanting gut microbes from one pre-intervention obese kid into germ-free mice increased adiposity and inflammation compared to transplanted microbes from the same kid post-intervention. Looks promising, but we need to see what happens when those pre- and post-intervention microbes are transplanted into another human. Another study by the same team placed obese adult subjects on similar diets, finding the same results.
In both cases, the new diets changed more than just the fermentable fiber content. They also incorporated “TCM food plants that are rich in dietary fiber, including adlay (Coix lachrymal-jobi L.), oat, buckwheat, white bean, yellow corn, red bean, soybean, yam, big jujube, peanut, lotus seed, and wolfberry,” as well as an extract of bitter melon, a medicinal food with suspected anti-diabetic effects. These are foods and supplements with bioactive compounds that likely affect obesity and metabolism apart from the fiber content. They may very well reduce obesity, but we cannot confirm that bacterial alterations are responsible.
Consumption of fiber that nourish our gut bugs—prebiotic, fermentable fibers and starches—appears to have anti-obesity effects.
Take resistant starch, for example. Although no direct evidence exists that RS lowers body weight, it has been shown to acutely increase fat oxidation and reduce fat deposition in adipose tissue. Taking a dose of resistant starch lowers appetite and subsequent food intake for several hours in a recent human study. Furthermore, resistant starch consistently feeds the gut bugs that produce butyrate in our colons. Butyrate is a short-chain fatty acid that increases energy expenditure in mice and, in humans, activates receptors involved in energy homeostasis. Still no proof that RS-mediated butyrate increases weight loss, but it’s a promising lead.
One study found that oligosaccharides, another class of prebiotics, increased satiety hormones and led to weight loss in overweight people. The low-prebiotic control group gained weight and had no improvement in hunger. However, calorie intake wasn’t controlled, so the prebiotic group ate fewer calories (because they weren’t as hungry) and thus lost weight. Skeptics would say, “See, it was calories all along!” I say, “Yeah, but the prebiotics made the calorie reduction sustainable!”
Another prebiotic, galacto-oligosaccharides (GOS), can lower levels of the stress hormone cortisol. Chronically elevated cortisol levels are strongly linked to belly fat, and people under a lot of stress are prone to choose fattening junk food over healthier fare.
Although the direct clinical evidence is lacking, it’s reasonable to assume that improving insulin sensitivity, increasing production of satiety hormones, reducing excess cortisol, and potentially increasing energy expenditure via short chain fatty acid production could help a person lose weight.
That said, a recent study raises the possibility of fiber behaving badly in a certain segment of the population. In a group of mice, scientists removed the genes coding for toll-like receptor 5 (TLR5), which keeps pathogenic microbes from entering circulation, is a major component of the innate immune system protecting against infections, and prevents bacterial overgrowth. Mice without TLR5 are prone to developing inflammatory bowel diseases, fatty liver, and metabolic syndrome. In this latest study, the TLR5-knockout mice developed the worst cases of metabolic syndrome in response to dietary fiber.
And those mice who got the worst cases of metabolic syndrome also produced the most short-chain fatty acids (SCFAs). SCFAs are the product of bacterial fermentation of dietary fiber. There are three major kinds: butyrate, which is primarily used by colonic cells and has a consistent link to improved metabolic health; propionate, a substrate for gluconeogenesis (glucose synthesis) in the liver; and acetate, 70% of which ends up in the liver as substrate for long-chain fatty acid synthesis. The lack of TLR5 led to unchecked bacterial overgrowth, and the teeming masses of bacteria were overproducing short-chain fatty acids which were stimulating the creation of new fat in the liver. Based on the metabolic fate of various SCFAs, excess acetate was the likely culprit. Many experts believe fatty liver sets a person up for type 2 diabetes and obesity.
These were mice, though. While TLR5-knockout mice get fat on fibrous diets, humans without TLR5 are actually less likely to become obese and more likely to get type 2 diabetes. Obesity is in many respects a defense mechanism for bodies overburdened with available energy; it’s safer to store excess nutrients in body fat than to let free fatty acids and glucose circulate indefinitely. TLR5 issues are certainly bad for people, but I don’t think many people have to worry about getting fat from fermentable fiber.
My gut sense is that the gut biome is a factor in weight loss, but probably not the biggest. But around the margins? For people who just need to tweak something for those stubborn few pounds? Normalizing testosterone levels, tamping down elevated cortisol, boosting satiety hormones, improving insulin sensitivity, increasing beneficial gut bacteria, and reducing lipopolysaccharide toxicity can all, in a roundabout way, help you lose weight and improve your metabolic health and resistance to obesity.
And it’ll certainly improve your overall health, which is what we’re really after. Right?
Let’s hear from you. Has improving your gut health directly led to weight loss?
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