Leaking Gut, Leaking Blood Vessels, Leaking Blood Brain Barrier

In today's open access paper, researchers attempt to throw a big tent over three distinct issues in the aging of the body and brain. Firstly, the intestinal barrier fails, allowing bacteria and bacterial metabolites into tissue and the circulation, where they can provoke dysfunction and inflammation. Secondly, blood vessels become leaky, harming surrounding tissues by allowing excessive fluid, inappropriate molecules and cells to escape. Lastly, the blood-brain barrier leaks; this is a more specialized barrier layer surrounding blood vessels in the brain, and when it leaks, the passage of unwanted cells and molecules into the brain again produces dysfunction and inflammation.

Can one really draw a circle around these three quite different phenomenon and talk about a unified "leaky syndrome", as the authors of today's paper do? Perhaps so if these issues largely begin with intestinal barrier dysfunction, allowing gut microbes and their inflammatory metabolites into the bloodstream to cause increased dysfunction in blood vessel walls. That this is the primary issue has yet to be determined, but given that we are entering an era in which the aged gut microbiome is both accurately measurable and can be rejuvenated via techniques such as fecal microbiota transplant, flagellin immunization, and so forth, I'd imagine much more will be known a decade from now.

Treating Leaky Syndrome in the Over 65s: Progress and Challenges

Aging is a natural process associated with decreased physiologic function in all organs, i.e. it not only affects our immune system, but also affects all tissues and cells, resulting in increased risk of several chronic diseases and vulnerability to death. The gut microbiome is now recognized as one of the key elements to maintaining host health1 and contributing to disease progressions such as high abundance of pathogenic bacteria (such as Escherichia coli, Staphylococcus aureus, and Clostridium difficile) and low abundance of short-chain fatty acid producing bacteria such as Bifidobacterium, Faecalibacterium, Roseburia. Several studies over the past few years revealed that the gut microbiome and its composition changes with age which could have significant implications on overall health during aging, however, the mechanisms by which it impacts the biology of aging remain largely unknown.

The microbiome is composed of diverse microbes i.e., bacteria, archaea, viruses, eukaryotic microbes, and fungi, that have lived in and around our body since birth. The gut and skin are the most extensively colonized regions of our body, while other areas including the mouth, eyes, ears, and reproductive organs also harbor dense populations of specific microbes. These microbes establish a symbiotic relationship with the host, playing a crucial role in regulating essential functions such as protection against pathogens, immunomodulation, and maintaining the structural integrity of the gut mucosal barrier, indicating a strong association between abnormalities in gut microbiota and the development of a wide range of diseases including autoimmune disorders, depression, and neurodegenerative diseases such as Alzheimer's disease and metabolic disorders.

However, the mechanisms by which the microbiome contributes to the development of these diseases are unclear. There can be several mechanisms but inflammation is a key suspect. Low-grade inflammation is often higher in older adults but the source of inflammation remains largely elusive. Growing evidence indicates that gut dysbiosis, characterized by an imbalance in gut microbial composition, tends to escalate with age. This dysbiosis, in turn, contributes to increased gut permeability, often referred to as "leaky gut". This heightened permeability facilitates the passage of pro-inflammatory substances such as bacterial toxins and lipopolysaccharide (LPS) from the gut lumen into the bloodstream or mucosal immune system, thereby triggering inflammation. Elevated inflammation is also known to increase the permeability of other epithelial and endothelial barriers such as intestinal epithelia (leaky gut), blood vessel endothelia (leaky vessels), blood-brain barrier (BBB) (leaky brain), and others, and collectively called "leaky syndrome". The link between leaky syndrome with chronic inflammation and microbiome dysbiosis in aging biology remains poorly understood.


Does anyone have an idea as to how prevent brain barrier or blood vessel deterioration?

Posted by: Danny at September 18th, 2023 3:10 PM


'...how prevent brain barrier or blood vessel deterioration?'

While you cannot completely prevent these processes, you can take several steps to promote brain health and reduce the risk of BBB dysfunction and blood vessel deterioration:
Eat a Brain-Healthy Diet:
Consume a balanced diet rich in fruits, vegetables, whole grains, lean proteins, and healthy fats.
Include foods rich in antioxidants like berries, leafy greens, and nuts to protect blood vessels and reduce oxidative stress.
Manage Blood Pressure:
High blood pressure can damage blood vessels over time. Monitor your blood pressure regularly and take steps to manage it through diet, exercise, and, if necessary, medication.
Maintain a Healthy Weight:
Obesity can increase the risk of vascular problems. Aim to achieve and maintain a healthy weight through a balanced diet and regular exercise.
Stay Physically Active:
Regular exercise promotes good circulation and helps keep blood vessels healthy. Aim for at least 150 minutes of moderate-intensity aerobic activity per week.
Manage Stress:
Chronic stress can negatively impact blood vessels and the BBB. Practice stress-reduction techniques like mindfulness meditation, deep breathing exercises, or yoga.
Control Blood Sugar:
High blood sugar levels can damage blood vessels. If you have diabetes or prediabetes, work with your healthcare provider to manage your blood sugar effectively.
Avoid Smoking and Excessive Alcohol:
Smoking and excessive alcohol consumption can harm blood vessels and increase the risk of BBB dysfunction. Quit smoking and limit alcohol intake.
Stay Hydrated:
Proper hydration is essential for maintaining blood vessel health and blood flow. Drink an adequate amount of water daily.
Get Quality Sleep:
Aim for 7-9 hours of quality sleep per night. Poor sleep can contribute to vascular issues and cognitive problems.
Manage Chronic Health Conditions:
If you have conditions like high cholesterol, atherosclerosis, or autoimmune disorders, work closely with your healthcare provider to manage them effectively.
Consider Supplements:
Some supplements like omega-3 fatty acids, antioxidants (e.g., vitamin C and E), and Coenzyme Q10 may support vascular health. Consult your healthcare provider before taking any supplements.
Stay Mentally Active:
Engage in cognitive activities such as puzzles, reading, or learning new skills to keep your brain active and healthy.
Limit Exposure to Toxins:
Minimize exposure to environmental toxins and pollutants, as they can contribute to BBB dysfunction and vascular problems.
Genetics and aging also play a significant role in the health of your blood vessels and the BBB. Regular check-ups with a healthcare provider can help monitor your overall health and detect any early signs of vascular or brain-related issues.

Posted by: Jones at September 18th, 2023 4:28 PM


Thanks, your advice is generally good for health.

One supplement I am familiar with that may benefit the blood vessel lumen is Pycnogenol, or pine bark extract.

- https://pubmed.ncbi.nlm.nih.gov/22240497/
- D.F. Fitzpatrick, B. Bing and P. Rohdewald, "Endothelium-Dependent Vascular Effects of Pycnogenol," J. Cardiovasc. Pharmacol. 32(4), 509-515 (1998).
- K. Nishioka, et al., "Pycnogenol, French Maritime Pine Bark Extract, Augments Endothelium-Dependent Vasodilation in Humans," Hypertens. Res. 30(9), 775-780 (2007).

Posted by: Danny at September 18th, 2023 8:53 PM

I would think Calcium AKG and Taurine would be 2 supplements good for that.

Posted by: Mike Best at September 19th, 2023 7:15 AM

The most powerful polyphenol of all is dephinidin, best from macqui berries. Good for stabilising vascular endothelium and BBB. Useful for gut integrity also.

Posted by: JLH at September 19th, 2023 3:28 PM

@JLH Delphinidin - there are also other sources, like european blueberry (there are supplements standardized for delphinidin), pomegranate fruit, aronia berries, chinese skullcap flowers.

Posted by: SilverSeeker at September 21st, 2023 8:56 AM

@JLH @SilverSeeker

Thanks for the information, didn't know about Delphindin.


Posted by: Danny at September 21st, 2023 5:30 PM

re delphinidin

So far as I can tell from the research, there are only about 5 polyphenols really worth bothering about out of the present estimation of circa 4,000 - 6,000 known polyphenolic molecules. Of the polyphenols, the anthocyanins are most effective ( circa 4-600).

Of those, there are 4-5 which stand out
The best are cyanidin and delphinidin. Quercetin and epigallocatechin are pretty useful too - the latter has a different pathway.

Of the delphinidins, the dephinidin sambubioside and rutinosides stand
out. Delphinidin is present in blueberries, aronia and elderberries in goodly amounts but about the highest (34% solid delphinidin) is maqui berries.
Tartary buckwheat ( anthocyanidin + senomorphic ) is interesting too.

Posted by: JLH at September 24th, 2023 3:43 PM

Reason mentions Fecal Transplant. He's also recently mentioned a company that seems quite credible that can supply this in pill form from "carefully selected young donors".
I'm quite hesitant however after looking into it. It seems that you are assigned a donor that lives nearby who prepares the pills themself…. Anyone tried this ?

Posted by: August33 at September 24th, 2023 10:24 PM
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