Learning Objective
There are multiple ways that the structure of the microbial community can be influenced, including host genetic diet, infections, or medical interventions (such as antibiotics). (Strachan, 2000) proposed the hygiene hypothesis of antibiotic usage and lifestyle alterations that limit microbial exposure were predisposing populations of people in developed countries to autoimmune diseases, and we will examine dysbiosis and look at the the factors influencing our health and the development of gut dysbiosis.
Estimated time: 15 mins.
Negative impacts
In the last ten years, evidence has emerged of significant changes in the structure of microbial communities, and it is speculated that these observed changes in microbial composition are contributing factors to the initiation and/or persistence of many of these diseases in patients with diabetes (Karlsson et al., 2013), asthma (Abrahamsson et al., 2013), allergies, autism (Parracho et al., 2005) and inflammatory bowel diseases (IBD) such as Crohn’s and ulcerative colitis (UC) (Frank et al., 2007). Gut Microbial health has become more relevant to healthcare practitioners and the public in view of the role of dysbiosis in Covid-19 and Obesity, but also Non-communicable diseases (NCDs) are now the leading causes of death and disability globally, killing more than three in five people worldwide NCD’s are responsible for more than half of the global burden of disease. Though NCDs are often associated with older people, 15 million deaths caused by NCDs each year occur before the age of 70 (“premature deaths”).
Without significant efforts to address the key risk factors and underlying social determinants driving NCDs, the economic and social toll of burgeoning numbers of people affected by NCDs in developing countries will continue to grow, exacting not just an emotional suffering cost but also an economic cost. People are less productive, they work for fewer years and die prematurely. If the upward trend of NCDs continues this is estimated to cause a cumulative loss of output of $47 trillion between 2011 and 2030
Antibiotics and Dysbiosis
So, before we look at the factors influencing the gut is important to understand that there are limitations in terminology – so please refer to this glossary entry.
On a personal note, my story was hugely impacted by the biome that when tested was less than 2% diverse. Over my lifetime, I was prescribed 57 antibiotics.
Total antibiotic counts:
- Amoxicillin x 27
- Penicillin V x 11
- Erythromycin x 3
- Co-amoxiclav x 2
- Metronidazole x 1
- Cefalexin x 5
- Flucloxicillin x 5
- Doxycycline x 1
- Trimethoprim x 2
Antibiotics certainly seem to be a serious cause of gut dysbiosis. Antibiotic use was associated with significant reductions in Bifidobacterium and Lactobacillus and increases in E. coli strains, in particular, the Amoxicillin (27 lots) resulted in a serious lack of diversity of Bifidobacterium, Lactobacillus, Enterococcus and Enterobacteriacea – which can be seen here in my original Gut Microbial analysis
A 2020 Meta-analysis of antibiotics during childhood reported that macrolide antibiotics such as erythromycin reduced diversity in the gut richness for twice as long as penicillin. These antibiotics are often used as an alternative if allergic to penicillin and have been shown to impact the gut for up to two years post-treatment.
The Gut Microbiome, Obesity, Metabolic Syndrome – Driving metaflamation
People with Obesity show increased GM dysbiosis, and these microbial changes are also seen in many of the Obesity-related diseases e.g., T2D, IHD and some cancers. The UK Office for National Statistics (ONS) reported that 28% of UK adults are obese, and a further 36% are overweight in 2021 Obesity increases our likelihood of Type-2 Diabetes, Hypertension, Heart Disease, stroke, and certain cancers, and is the cause of significant premature disability. At the phylum level, obese individuals have been shown to have a higher Firmicutes/Bacteroidetes ratio. At the species level, a loss of diversity has been noted in obese individuals accompanied by an increase in gut wall permeability, which is likely to explain the increased low-grade systemic inflammation( Metaflamation).
Lipopolysaccharide (LPS) & Stress
An unhealthy diet encourages more LPS release and negatively impacts gut barrier integrity. It is classified as an endotox, LPS is the structural component of the outer membrane of gram-negative bacteria and is linked to a diet high in fat and sugar (typical of Western diets) poor diets essentially ‘feed’ the gram-negative bacteria and the balance of these bacteria increase and population expands. As these microorganisms are broken down, LPS is released into the bloodstream LPS and other metabolites activate the release of many pro-inflammatory cytokines. ( Immune system messengers) (There are studies that show a positive impact on LPS such as this one on probiotic LGG and a more recent one here. )
Cortisol also has an anti-inflammatory role in the body. One of the ways it acts is through suppression of the production of pro-inflammatory cytokines. Cytokines are chemical messengers which help regulate our immune system. Becoming less sensitive to cortisol means this suppression action becomes less effective. When you are chronically stressed and your body’s levels of cortisol and cytokines are affected, you are more likely to have low-grade inflammation, which is something you don’t want. Combine poor lifestyle choices, poor food choices and increased levels of stress, and those high levels of cortisol can weaken your immune system. The cytokines are likely to increase the risk of other NCDs by triggering inflammation within adipose (fat) and hepatic(liver) tissues leading to an increase in glucose production and fat storage associated with metabolic dysfunction, Type 2 Diabetes and Obesity.
Note – Bifidobacteria and high output short-chain fatty acids producers such as Roseburia promote a robust gut barrier which prevents LPS from leaking into the bloodstream through the production of SCFA. SCFAs can help block the inflammatory mediator activation by LPS and also Conversely, a
Gastroenteritis
Infections with pathogenic bacteria can also lead to gut dysbiosis, if acute infective gastroenteritis treatment helps to flush the causative pathogens out, the resident microbes are also removed. Your appendix acts as a microbial ‘reservoir’ to recolonise the gut, however, some species can be lost completely after a severe bout of gastroenteritis. This study investigated changes in the gut microbiome following an episode of acute gastroenteritis, and there are links to infections being associated with irritable bowel syndrome which is common after presumptive viral gastroenteritis this study after norovirus.
Learning Outcome
You will have an overview on of the chronic non-communicable diseases (NCDs) that are associated with gut dysbiosis, mechanisms linking dysbiosis and chronic disease, and the factors that impact the gut positively.
