Metabolic Health and the Microbiome
She had been told her blood tests were normal, a little on the high side but normal “come back in a year”.
She carried on with business as usual, eating healthy but noticed a little weight gain, sleep fraying at the edges, mood dipping more and anxiety creeping up. Then the shock of the next lot of bloods showing she has high cholesterol, blood sugar is also out of range. The scary part - risk of “cardiovascular disease” and “type 2 diabetes” are mentioned, landing like a lead balloon.
By the time she sat down with me it felt like it was all too much and out of control. “I've been eating really well, doing all the right things” she says, “What's going on? What am I doing wrong?”
Sound familiar?
She's not doing anything wrong. Her body was changing, her health landscape was changing, and no-one had thought to prepare her for this.
I see some version of this most weeks. Cholesterol climbing in the background alongside perimenopause. Blood sugar that will not regulate no matter how clean the diet gets. A body composition that shifts without any change in what a person is eating or how much they move.
The connection between our gut microbiome and metabolic health is an important one to explore, and fortunately it is one that we can support really well with the right dietary and lifestyle changes alongside other interventions. This is especially important alongside the now quite popular weight and diabetes management medications - glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and at particularly challenging life stages such as perimenopause.
What’s the gut got to do with it?
Research continues to reveal how various characteristics of the gut microbiome are associated with states of metabolic health. Recent research shows that the state of one’s gut microbiome is a significant factor when it comes to metabolic risk factors, such as obesity, elevated blood sugar (hyperglycaemia), insulin resistance, imbalanced blood lipids including cholesterol (dyslipidaemia), all of which can increase a person’s risk for cardiometabolic diseases like cardiovascular disease (CVD) and Type-II diabetes mellitus (T2DM).¹
The microbial ecosystem in the gut can influence metabolic health through various factors including:
Appetite regulation
Insulin sensitivity and blood glucose regulation
Gut barrier integrity
Regulation of inflammatory processes
Production of microbial metabolites
Gut dysbiosis and metabolic dysfunction
An unbalanced microbial gut ecosystem (dysbiosis) can negatively affect metabolic health. In a dysbiotic state, the microbial metabolites produced by microbes in the gut disrupt the intestinal barrier and promote systemic inflammation which drive insulin resistance and metabolic dysregulation.²
For example, the bacterial metabolite trimethylamine when oxidised to trimethylamine N-oxide (TMAO) can promote factors that may, in some individuals, increase the risk of atherosclerosis (high cholesterol), CVD (heart disease), and diabetes.¹
Current evidence shows further research is needed to establish whether TMAO plays a causative role or whether it is a biomarker correlated with common signs of metabolic dysfunction.²
While there is individual variation and a multitude of factors influencing metabolic homeostasis, it has been acknowledged that a pattern of gut dysbiosis often associated with metabolic concerns such as metabolic syndrome and T2DM (type-2 diabetes) may be characterised by³:
An overall reduction in diversity of species in the gut microbiota
Higher numbers of pathobionts (innocuous microorganisms which can sometimes turn nasty, given the right conditions), often accompanied by increased production of endotoxins (toxins produced by “bad bugs”) such as lipopolysaccharide (LPS)
Decreased abundance of the beneficial commensal Akkermansia muciniphila, a species which is known to exert numerous benefits for metabolic health
Gut dysbiosis can negatively impact immune signalling locally at the gut and system wide, compromising intestinal barrier permeability (aka leaky gut), and promoting inflammation - all factors known to be associated with states of metabolic dysfunction.¹
Helpful microbes and their metabolites
There is no specific microbial signature that is associated with healthy metabolic function across the board, as the ever-expanding research base will often remind us. What is important to understand, is the functional capacity of our gut microbes. Can the metabolic activity of our gut microbes help create the right microenvironment to support metabolic homeostasis in our bodies?
That’s the question to ask, and that’s something a practitioner like myself can help uncover the answer to by assessing your diet, lifestyle, and even your microbiome directly with testing when appropriate. Just like a dysbiotic gut can create conditions for metabolic dysfunction, there are certain traits we want to look for in a healthy microbiome which will support healthy metabolic function. These include²:
Maintenance of the gut barrier
Keeping inflammation in check
Regulating production of hormones involved in appetite, blood glucose, and insulin levels
Whilst there are a range of microbes which perform these functions, there is a specific one worth mentioning as it addresses all of the above, and that’s Akkermansia muciniphila (herein referred to as Akkermansia).
Amazing Akkermansia
This microbe is a crucial inhabitant of the gut who lives in the intestinal mucus layer, consuming mucin (a component of mucus), which helps stimulate more mucus production, thereby protecting the integrity of the gut barrier.⁴
Akkermansia also up-regulates proteins that keep the tight junctions between cells of the intestinal lining together. Its ability to maintain the gut barrier means Akkermansia can help reduce the systemic inflammation that can happen when endotoxins (those toxins from the “bad bugs”, like LPS) from opportunistic or pathogenic microbes penetrate the gut lining.⁴
This is important, as inflammation is a key feature seen in metabolic disease. Akkermansia has also been shown to produce helpful metabolites like certain SCFAs which help to:
Increase insulin release after meals by upregulating GLP-15
Support fat metabolism and energy balance⁴
Feed other beneficial microbes in the gut, such as Faecalibacterium prausnitzii, a well-known butyrate producer⁴
Akkermansia has been shown to be present in higher amounts in people with lower body fat and good metabolic health,⁴ and while it’s always important not to equate correlation with causation, this is an interesting observation.
Feeding the Akkermansia that already resides in your existing gut ecosystem may be a more sustainable strategy than relying on Akkermansia supplements.⁶
This microbe is highly sensitive to oxygen, which poses a manufacturing challenge in the process of creating live probiotic supplements, and is one of the reasons why its pasteurised or heat-inactivated form (sometimes referred to as a post-biotic) seems to be more effective for metabolic health concerns like weight management.⁷
Building up, diversifying, and nourishing our existing gut microbes is one of the best things we can do for overall health, including metabolic health.
Modulating the microbiota for metabolic benefit
Addressing chronic inflammation and insulin resistance as core drivers of metabolic dysfunction is something that can be achieved by modulating the gut microbiota.¹ Naturopaths are exceptionally well-placed to support people in this area of health, as dietary and lifestyle modifications can serve as a foundation to return to, especially alongside medications or supplements. I use a range of strategies to modulate the microbiome beneficially for metabolic health.
Food for our friends in the gut
Fermentable plant fibre is the primary fuel source for our gut microbes, and helps to foster a diverse ecosystem in the gut. Prebiotics in particular support growth of beneficial bacteria, increasing SCFA synthesis and strengthening the gut barrier.⁸
Inulin alters the ratio of certain bacterial phyla relative to other groups in a way that supports healthy body composition, while fructo- and galactooligosaccharides (FOS and GOS) selectively increase helpful microbes such as those from the genera Bifidobacterium and Akkermansia, helping to support the gut barrier, improve insulin sensitivity, and reduce inflammation.⁸
Plants are an excellent source of fermentable fibre, but when you are able to eat a great diversity of different coloured plants, you’re also getting the added benefit of polyphenols. Metabolic health effects (particularly for insulin resistance) have been observed with foods rich in the polyphenols epicatechin (found in green tea, cacao, apples) and anthocyanins (in red and purple plants like berries, red fleshed dragonfruit, radishes, red cabbage).⁹
Probiotics
Probiotics can be an effective way of modulating the gut microbiota. Some genera such as Bifidobacterium and Lactobacillus are widely researched as probiotic supplements with improvements observed for insulin sensitivity and reduction of inflammation,¹ but the research on probiotics for metabolic health outcomes often only highlight the species and not the specific strain. In a previous article, I discussed the importance of knowing which specific strains are present in a probiotic product, because this can help us to understand its mechanism of action, and also to examine the research more precisely.
Short-chain fatty acids (SCFAs)
Acetate, propionate, and butyrate are notable SCFAs produced by gut bacteria as part of their metabolism. Each of these metabolites serve distinct physiological roles, and each of them may influence metabolic factors such as satiety signalling, insulin sensitivity, and inflammatory processes.²
Butyrate in particular is known to promote colonic health, and has been shown to support release of hormones which regulate satiety and appetite like GLP-1 and peptide YY, as well as anti-inflammatory effects.¹
Research assessing either supplemented SCFAs or fibre (to increase SCFA production in the gut) for insulin sensitivity has shown that individual responses can vary significantly, with a person’s existing gut ecology being an influential factor.¹⁰
In my practice I aim to help restore the ecology of the gut, nurturing the microbes which will subsequently produce enough butyrate and other SCFAs so that patients can experience the systemic benefits of that, metabolic or otherwise.
GLP-1 medications and the microbiome
While a healthy gut microbiome supports metabolic health, it is also an important determinant of how effective certain medications can be. There has been a growing interest in GLP-1 receptor agonists, medications (e.g. semaglutide) which are commonly prescribed for weight loss. GLP-1 is a hormone naturally produced in the small intestine and helps regulate blood glucose, insulin secretion, and satiety.¹¹
I’ve been continuously learning about GLP-1 medications and would like to express my gratitude to Wendy Burke, a practitioner who is doing great work in this space to help patients and practitioners understand their impact.
Research has shown that a person’s baseline microbiota can impact their response to GLP-1 medications, with some people responding more favourably than others.¹² Additionally, use of these medications can reshape the gut microbiota, as can other medical interventions such as bariatric surgery.¹³ Shifts in microbial profiles characterised by beneficial species like Akkermansia have been observed with GLP-1 medication use.¹²
In addition, microbiome profiles characterised by elevated levels of pro-inflammatory microbes have been associated with suboptimal metabolic responses, potentially compromising host responses to GLP-1 medications.¹⁴ This demonstrates a bidirectional relationship, in that the microbiome affects the release and function of the body’s own GLP-1 in the gut, as well as the effectiveness of GLP-1 medications, but the GLP-1 medications may also alter the profile of the gut microbiome. It remains to be seen whether the beneficial microbial shifts observed with GLP-1 medications are a cause or a consequence of weight loss, but this is a hot topic of research which continues to grow.
Whilst GLP-1 medications can be a useful tool for some people looking to improve their metabolic health, they may also increase the risk of low blood pressure, sleep disturbances, headaches, joint pain, gastrointestinal disorders, and potential kidney and pancreas issues.¹⁵ For this reason, it is always advised to consult your prescribing medical practitioner regularly so they can monitor your response to the medication and alter your dosing when appropriate.
Naturopaths are well-placed to support the gut microbiome and metabolic health and in turn, to provide the ideal conditions for GLP-1 medications to do their job. Through targeted and personalised dietary and lifestyle changes, we can not only help sustain the benefits of these medications, but also help ease the transition that comes after taking them, so that a healthy weight can be sustained beyond medication use.
Metabolic health through menopause
Supporting metabolic health can become more of a challenge as we move through the important transition that is perimenopause. I discuss how hormonal changes through the menopausal transition influence the gut microbiota in this article, but let’s look at its connection with metabolic health specifically. There is a whole area of research examining the ‘estrobolome’, a term which describes the collective microbial gene pool that plays a role in how oestrogen is metabolised in the body.¹⁶
Distinct microbial signatures have been observed in women experiencing menopausal symptoms compared to those who do not, alongside increased activity of metabolic pathways related to carbohydrate metabolism and cardiovascular disease in those women who do experience unpleasant symptoms of perimenopause.¹⁷
Irrespective of whether symptoms are present through menopause, it is known that the declining oestrogen characteristic of menopause coincides with a reduction in gut microbiome diversity,¹⁶ which provides a great reason to support your gut and feed your microbes well.
Takeaways
Research in this space is continuous and we have learned a significant amount of information about how different microbial characteristics may be associated with varying states of metabolic health. Understanding individual differences in gut microbiota composition and metabolic function are key for improving health outcomes for those dealing with metabolic health concerns,¹⁸ and this is exactly what I aim to do in clinical practice with my patients. We are all so unique, so a personalised approach is always going to be the most supportive, no matter your health concern.
If getting on top of your metabolic health is a priority and you would like further support in this area, you are welcome to book a Discovery Call with me so we can assess next steps for you. Or perhaps you’re feeling the call for deep rest and to slow the pace of life down just a little. My Microbiome Retreat this October may be the perfect opportunity for you to experience a deeply restful reset, including delicious, lovingly prepared food to nourish your microbiome.
References
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