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Human Microbiota and Toxin Metabolism

by luciano

Abstract
The human gut microbiota is a complex ecosystem of microorganisms that plays a central role in digestion, immune function, metabolic regulation, and the handling of dietary and environmental toxins. Through the fermentation of non-digestible carbohydrates and fibers, gut bacteria produce short-chain fatty acids (SCFAs) such as butyrate, acetate, and propionate, which act as key metabolic mediators between the microbiota and the host. These metabolites serve as essential energy substrates for intestinal epithelial cells, support gut barrier integrity, and modulate inflammatory responses and systemic metabolism.
In addition to carbohydrate fermentation, the gut microbiota is involved in the biotransformation of xenobiotics, including environmental toxins, drugs, and food-derived compounds, influencing their bioavailability and toxicity. Conversely, exposure to antibiotics, pollutants, alcohol, and ultra-processed foods can disrupt microbial balance, leading to dysbiosis, increased intestinal permeability, inflammation, and metabolic disorders.
This article explores the bidirectional interactions between the gut microbiota and toxins, the different types of bacterial fermentation (saccharolytic versus proteolytic), and the concept of energetic symbiosis between microbes and the human host. Understanding these mechanisms highlights the crucial role of diet—particularly dietary fiber—in maintaining microbiota functionality, metabolic health, and resilience against toxic and inflammatory challenges.

Keywords
Gut microbiota; Short-chain fatty acids (SCFAs); Dietary fiber; Butyrate; Fermentation; Metabolic health; Inflammation; Gut barrier; Dysbiosis; Toxin metabolism; Gut–liver axis; Energetic symbiosis
1) Human microbiota: definition and role
Definition
The human microbiota is the collection of microorganisms (bacteria, viruses, and fungi) that live on and within the human body, particularly in the gut, and contribute to critical metabolic and immune functions. (Nature)
Main functions
Digestion and fermentation of non-digestible fibers → production of short-chain fatty acids (SCFAs), such as butyrate. (MDPI)
Modulation of energy and glucose metabolism. (Nature)
Maintenance of the immune barrier and protection against pathogens. (Nature)
Involvement in the gut–liver and gut–brain axes. (Atti dell’Accademia Lancisiana)

2) Interactions between the microbiota and toxins
2A – Microbiota → toxins/metabolites
The microbiota:
Ferments dietary fibers [1], producing beneficial metabolites (SCFAs). (MDPI)
Metabolizes xenobiotics (environmental toxins, drugs, additives), influencing their chemical form and toxicity. (MDPI)
Contributes to the intestinal barrier, limiting the absorption of harmful substances. (Atti dell’Accademia Lancisiana)
Recent research:
1. Fan & Pedersen (2020): link the gut microbiota to the metabolism of food-derived compounds and toxins in humans. (Nature)
2. Tu et al. (2020): review on the microbiome and environmental toxicity (concept of gut microbiome toxicity). (MDPI)

2B – Toxins → microbiota
Some agents negatively impact the microbiota:
Antibiotics → intestinal dysbiosis
Pesticides/heavy metals → alteration of microbial diversity
Alcohol and ultra-processed foods → emerging negative effects
Evidence examples:
Environmental and dietary factors can alter microbial balance and increase inflammation. (ScienceDirect)

2C – Effects of dysbiosis
Dysbiosis (microbiota imbalance) may lead to:
Intestinal inflammation
Increased intestinal permeability (leaky gut)
Metabolic disorders (obesity, insulin resistance)
Recent scientific evidence:
Reviews linking microbiota composition to metabolism and human health. (Nature)

3) Factors influencing the microbiota
Factor
Effect
High-fiber diet
↑ diversity and SCFA production (MDPI)
Polyphenols (fruit/vegetables, tea, wine, olive oil)
Positive modulation of the microbial community
Antibiotics
↓ biodiversity, ↑ dysbiosis
Alcohol
May damage the mucosa and promote permeability
Ultra-processed foods
Associated with dysbiosis (mechanisms still under investigation)
Key research:
1. Charnock & Telle-Hansen (2020): effects of fiber on the microbiota and metabolic health. (MDPI)
2. PubMed reviews (2023–2024): fiber and microbiota modulation with clinical implications in metabolic diseases. (PubMed)

4) Toxin elimination: integrated physiological pathways
Liver
Phase I: structural modification of toxins (oxidation)
Phase II: conjugation → increased solubility
Elimination via bile → intestine
The microbiota may modify these metabolites and influence their recirculation
Kidneys
Filter the blood
Eliminate water-soluble toxins through urine
Intestine + microbiota
Excretion of toxins via feces
Physical and metabolic barrier against the absorption of harmful compounds
Lungs and skin
Elimination of CO₂ and volatile compounds
Minor role in the detoxification of more complex molecules

5) Integrative key concepts
SCFAs and health
Products of bacterial fiber fermentation (e.g., butyrate) not only provide substrates for intestinal cells but also modulate inflammation and systemic metabolism. (MDPI)
Microbiota and the gut–liver axis
Microbial metabolites influence hepatic metabolism, with potential effects on toxin handling and lipid metabolism. (Nature)
Diet and metabolic diseases
Microbiota changes associated with low fiber intake are linked to obesity and type 2 diabetes. (PubMed)

Mini-summary
1. The gut microbiota is an ecosystem of microorganisms that supports digestion, immunity, and metabolism; its alteration (dysbiosis) is associated with metabolic diseases. (Nature)
2. Non-digestible dietary fibers are fermented by gut microbes into beneficial compounds (SCFAs). (MDPI)
3. Microbiota and toxins influence each other: the microbiota can degrade or transform xenobiotics, while substances such as antibiotics and pollutants can alter microbial composition. (MDPI)
4. The body eliminates toxins through the liver, kidneys, intestine (with microbiota involvement), lungs, and skin.

Low-grade inflammation and the brain

by luciano

“What is inflammation?
We usually talk about “inflammation” in relation to infections and injuries. When the body is infected, the immune cells recognize the ‘non-self’ molecules and produce inflammatory factors, called “cytokines”, to coordinate the fight against the infection. Cytokines signal other immune cells and bring them to the site of infection. Inflammation is clinically assessed by measuring cytokine concentrations or other inflammatory markers in the blood and is used as a sign of infection.
What is low-grade inflammation?
It is a question that remains hard to answer. Low-grade inflammation is usually defined as “the chronic production, but a low-grade state, of inflammatory factors”. Conditions characterized by low-grade inflammation are for instance obesity (1), depression (2) or chronic pain (3). Low-grade inflammation does not come from an infection but several physiological mechanisms are involved. Concentrations of inflammatory factors in these conditions are overall slightly higher than in healthy populations, but still remain in the healthy ranges. It is therefore hard to determine whether a specific patient exhibits “low-grade inflammation” but it can be better defined at the level of a group of patients.
Inflammation and the brain
When we are sick, we often want to sleep, have reduced appetite, prefer to stay home alone, have difficulty concentrating and can be a bit moody. All these feelings and behaviors are induced by cytokines! Indeed, in addition to coordinating the fight against infection in the periphery of the body, cytokines also act in the brain and induce behavioral changes (4). All these behavioral changes are adaptive, with the purpose of limiting the spread of the infection and allowing the body to spare energy in order to fight the infection instead of, say, going out partying with friends.
However, the behavioral effects of cytokines are not always beneficial. When the cytokine signal is too strong or lasts a long time, such as in cancer patients during treatment with cytokines, these effects can become maladaptive and lead to more chronic and pathological behavioral alterations, such as depression (5). Inflammation is therefore one hypothesized contributor to depression (4). One critical difference between infection or cancer therapy and most cases of depression is, however, the level of production of inflammatory factors. Cytokine levels are high during immunotherapy, i.e., “inflammation”, while depression is characterized by a state of “low-grade inflammation”.
The proportion of subjects who suffer from depression is higher in conditions characterized by low-grade inflammation than in the general population. For instance, 20 to 30% of obese individuals suffer from depression while the prevalence in the general population is of 5-10% (6). While psychological factors are highly likely to be involved, we and others investigate the possibility that low-grade inflammation contributes to this psychiatric vulnerability (7). We have notably shown that low-grade inflammation is associated with behavioral changes in obese individuals, such as fatigue (8) or altered cognitive functions (9). One interpretation of this relationship is that the production of inflammatory factors at a low-grade state may be sufficient to induce behavioral alterations and therefore could be one factor participating to the vulnerability to depression.
Low-grade inflammation and chronic pain
The association between low-grade inflammation and behavioral alterations has caused the team of the Behavioral Medicine Pain Treatment Service at the Karolinska University Hospital in Stockholm (Sweden) to wonder whether low-grade inflammation could modulate the efficacy of behavioral treatments for chronic pain. Cognitive and behavioral strategies are indeed the targets of behavioral treatments for chronic pain and low-grade inflammation could prevent the effects of such treatments.
In collaboration with this group, we showed that treatment outcomes were improved in patients with chronic pain and low levels of inflammatory factors while patients with “low-grade inflammation”, i.e., with higher levels of inflammatory markers but still in the healthy range, exhibited less improvement (10).
Although this study was only exploratory, the findings suggest that low-grade inflammation may promote a state of resistance to behavioral treatment for chronic pain and give a potential explanation regarding non-responder patients.
About Julie Lasselin
Dr Julie Lasselin is a “psychoneuroimmunologist”, conducting research assessing the relationships between the brain and the immune system. She got her Ph.D. in 2012 in NutriNeuro in Bordeaux, France. She then has been working as a post-doc at the Department of Clinical Neuroscience (Psychology Division), Karolinska Institute and at the Stress Research Institute, Stockholm University in Stockholm, Sweden. Julie is currently a post-doc in the Institute of Medical Psychology and Behavioral Immunobiology in Essen, Germany and is affiliated to the Karolinska Institute and Stockholm University. Her research focuses on the contribution of inflammation on the development of neuropsychiatric symptoms in vulnerable populations, such as patients suffering from obesity and type 2 diabetes. She carries out both clinical observational studies and experimental studies using the model of administration of lipopolysaccharide (a component of bacterial shell) in humans. She also assesses more specifically the role of inflammation in fatigue and motivational changes, two symptoms that are highly sensitive to inflammation and may explain the psychiatric vulnerability of obese patients.”
References
1. Wellen, K.E. and G.S. Hotamisligil, Obesity-induced inflammatory changes in adipose tissue. J Clin Invest, 2003. 112:1785-8.
2. Dantzer, R., Depression and inflammation: an intricate relationship. Biol Psychiatry, 2012. 71: p. 4-5.
3. Parkitny, L., et al., Inflammation in complex regional pain syndrome: a systematic review and meta-analysis. Neurology, 2013. 80:106-17.
4. Dantzer, R., et al., From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci, 2008. 9:46-56.
5. Capuron, L. and A.H. Miller, Immune system to brain signaling: neuropsychopharmacological implications. Pharmacol Ther, 2011. 130:226-38.
6. Evans, D.L., et al., Mood disorders in the medically ill: scientific review and recommendations. Biol Psychiatry, 2005. 58:175-89.
7. Capuron, L., J. Lasselin, and N. Castanon, Role of Adiposity-Driven Inflammation in Depressive Morbidity. Neuropsychopharmacology, 2016 (in press).
8. Lasselin, J., et al., Fatigue symptoms relate to systemic inflammation in patients with type 2 diabetes. Brain Behav Immun, 2012. 26:1211-9.
9. Lasselin, J., et al., Low-grade inflammation is a major contributor of impaired attentional set shifting in obese subjects. Brain Behav Immun, 2016. 58:63-68.
10. Lasselin, J., et al., Low-grade inflammation may moderate the effect of behavioral treatment for chronic pain in adults. J Behav Med, 2016. 39:916-24.