Gut microbes linked with obesity and weight gain!

If you are obese and wondering how did you accumulated all that weight, well you could blame it to the bacteria living in your gut.

A new research has shown that inbred germ-free mice quickly gained weight when given gut bacteria derived from obese human twins than those mice which received gut bacteria from the lean twins. Scientists tested at least four such human twin pairs-derived gut microbes in the mice which all received the same kind and amount of the food.

Image curtsy: http://blog.fooducate.com/ 

The study suggests that the gut microbiota, which include plethora of microbes such as bacteria, fungi, archea living in the intestine, can affect the metabolism and thus weight gain.

Scientist know that humans and microbes live in close association with each other, so much so that in number our body harbors far more microbial cells, nearly 100 trillion, than our own cells, in the ratio of 1 to 10. Although these numbers may look frightening to a layman but they actually live in a mutually beneficial relations with our body.

Some of them live as commensals - living but not causing any harm, symbiotic –mutually helping each other and some of them may live as pathogens, causing harm such as well known pathogenic diseases.

It is therefore logical that if so many organisms are in or on us, they may also affect how we function as an organism, they should then also affect our metabolism, so to say.

And they do! It is known that any disturbances in our intestinal environment could lead to the growth of harmful microbes which may lead to chronic inflammatory diseases including obesity, metabolic disorders and infections.

Image Curtsy: spreadshirt.com

Scientist have shown earlier that an antibiotic-resistant gut bacteria, Clostridium difficile, known to affect and killing thousands in America, can be treated by transplanting microbiota from a healthy individual into an infected persons gut.

Scientists have also shown that the gut microbes also amend our immune system which helps us identify the foreign pathogens, antigens and harmful substances and eradicate them. The increasing cases of allergic and autoimmune disease in the developed countries are arguably believed to be related with disturbance in microbial habitat, our body, due to the hygienic living, leading to emergence of “hygiene hypothesis” to explain these increased incidences.

Previously, scientists have also experimentally shown that when the intestinal flora of the lean mice was given to the obese mice, they successfully controlled and decreased the body weight in obese mice. 

The study led by Jeffrey I. Gordon at Washington University in St. Louis, MO found that when mice with the lean microbiota were made to cohabitate with mice having obese microbiota much before they gained weight, and found that the populations of bacteria in the obese-type mice changed to those of their lean cage-mates, and that their weight did not increase as well. It is known that mice eat each other’s faeces, so this allowed the replacement of ‘obese’ microbiota, but this migration was unidirectional and microbiota from obese mice did not colonize in the lean mice gut.

Image Curtsy: www.vaccinationnews.com

However, interestingly enough, scientist also discovered that besides this there is strong correlation between the diet we take and how the gut microbes behave. When the researchers fed the mice a low fat diet rich in fruit and vegetables, the gut microbes from lean mice migrated to those with the obese type. But, when a high-fat diet low in fruits and vegetable was fed to mice, the microbe transfer did not occur and obese-type mice went on to gain weight.

This and many other studies clearly indicate that our relationship with the microbes is very intricate and scientists are unraveling these intricacies slowly but steadily. However, a lot remains to be learnt about various other players including genetics, environment, diet and diseases in the interaction of microbes and our body which benefits as well as harm each other.

Near-death experience explained!

A remarkable research in the neuroscience has provided some scientific basis for our long held beliefs about the near-death experiences.

 Many survivors narrate near-death experience as going through a tunnel in the extraterrestrial land adorned with flower valley, intense white light, meeting with long deceased loved ones, talking to them, appearance of angels and much more. 

Near death survivors narrate passing through a tunnel
Image courtsey: iStock.com

The scientists have wondered if brain activity in a near-death state can explain the near-death experience? What actually happens in the brain immediately after the death?

The general belief is that during a cardiac arrest the brain activity goes down or stops, so there seems no connection between near-death experience and brain activity.

Different brain waves associated with the brain activity in different states

Image courtesy: Art and Science of Meditation

But this belief challenges our understanding of brain and so far there is no clear scientific evidence of the neuro-physiological activity in brain during near-death state after a cardiac arrest, until now.

In a first of its kind study the neuroscientist at the University of Michigan in Ann Arbor performed a systematic study of the neurophysiology of the dying brain after a cardiac arrest in rats.  

The scientists found that all the animals studied invariably displayed a short-lived but highly synchronized and heightened brain activity in the first 30 seconds of cardiac arrest. This suggests that “the mammalian brain can, albeit paradoxically, generate neural correlates of heightened conscious processing at near-death”.

The study has been published in the journal Proceedings of the National Academy of Sciences, USA. The original article can be accessed here http://www.pnas.org/content/early/2013/08/08/1308285110.abstract

So how does this finding relate with the near-death experience? The researchers reasoned that near-death experience is nothing but increased brain activity and conscious processing, which could possibly be the source of highly vivid and lucid conscious experiences during clinical death after the blood stops flowing to the brain.

In the state of cardiac arrest there is progressive decrease of oxygen as well as of glucose, the main ingredients required for brain to survive and function, which induces characteristic conscious processing in brain resulting in heightened brain activity. It could be equated with the survival instinct of a dying brain.

Although more detailed studies are needed to fully understand this phenomenon, the study does provide “a scientific framework to explain the highly lucid and realer-than-real mental experiences reported by near-death survivors”.

Genetics of asthma

Asthma is the disease of airways, which include bronchi, bronchioles and alveoli in the lungs. Inflammation in these tube-like structures causes them to swell, secrete mucus, and clog the passages. It results in very low amount of air reaching to the lungs, causing breathlessness, chest tightness, difficulty in breathing and cough.

During the attacks, which can be caused by many reasons including allergens, pollution, sudden change in temperature, exercise, stress and many more, the tubes start constricting excessively blocking the flow of wind to the lungs.

It is not clear why some people are not affected by those same stimulants which cause asthma in others! The hereditary links have been suggested by many scientists. But, this suggestion can be questioned by the fact that many asthmatic children’s parents have never been diagnosed with asthma.

 Can this be due to the mutation in the genes acquired by parents, which latter on transmitted to the children?

The genetic link of asthma has been a point of debate for a long time now. Many genes have been identified which are suggest to be associated with the disease, but so far except for few, most of the associations have not been proved correct.

Children are the most affected from asthma as the disease, which first start with the allergic episodes and graduates to asthma attacks quickly. Some of those children get better with age and are able to manage their asthma with the modern and improved medicines and some changes in life style.

However a section of patients remain affected with the disease besides taking all those measures. They frequent to the hospitals, leaves from school and office, and also get affected by secondary infections of the lungs.

Scientists have been working to find reason for these differences. A new study has identified at least 15 mutations in the human gene that suggests link with childhood asthma. It is suggested that those patients whose asthma has genetic link are around 35% more likely to suffer from the disease as adult too.

The other indication of such association is that those with severe childhood asthma are more likely to have the disease as an adult.

Although at present it cannot be predicted with certainty which childhood asthma patients will be free from the disease and who will continue to have it as an adult, at most the new research on genetic link of asthma presents a hope that more focused studies will make our understanding better about the genetic association of this serious disease. 

Why do people commit suicide?

Human beings are definitely highest evolved animal species on the planet earth. The advantage that we get over our nearest ancestors is because we have well developed brain, which helped us become intelligent and civilized unlike other species.

Our brain has given us all the modern technologies and objects that makes our lives easy and comfortable. Brain has developed the concepts of modern science such as laws of physics and chemistry and biology, it helps run such a big and vast group of people that we call humanity on this planet despite many internal and external threats that we face on daily basis, with the potential to wipe out our existence.

The same brain also becomes a liability for some of our species members. If not controlled, the brain devises all kind of tactics to control the body and propel it to perform many functions which are averse to the very concept of a civilized world. Although individual’s body performs anti-social activities such as crimes like murder, rape, dacoity and burglary but the actor who plans and executes these acts is actually his brain. So much so that brain directly or indirectly sometimes causes the destruction of the very body in which it resides and we blame the individual that he has committed suicide.

According to an article published in 2012 in the International journal of environmental research and public health nearly 800,000 to a million people commit suicide every year and die. Suicide is the 10th leading cause of death worldwide. The rate of suicide is higher in men than in women, with ratio of 3- to 4-times more.

Why do people commit suicide? It is the question which everybody asks after such incidents are reported. There may be enumerable reasons and perspective when one tries to answer that question. The perspective of an expert such as psychiatrist and medical counselor will be far removed from an ordinary person on the street. One will find problem in how the person could not bear the pain of pervasive suffering that a depression creates, to as simple as that ‘he wanted to escape from all his problems that he thought were impossible for solve’.

There are other reasons such as psychotic, impulsive, philosophical yearning to depart, sense of guilt, and some mental illness such as schizophrenia. Nevertheless, in all these conditions eventually it is the person’s brain which is to be blamed.

The experts who study brain and suicide have been trying to understand this emotional negativity that brain creates. Out of many chemicals in the brain, experts associate this tendency with the serotonin. It is a neurotransmitter that helps transmit the neural signals and also sooths the mind. Studies indicate a link between suicide and the low level of serotonin in the brain. In some suicide victims, the brain has been found to retain this neurotransmitter by not allowing its absorption by the neural synapses. This results in calming effect and that is how the anti-depressant works. It is know that greater dose of anti-depressant propel suicidal thoughts. However, serotonin levels alone cannot lead someone to suicide.

However, experts believe that it is the brain which creates an alternative world in the mind of a suicidal person. In that alternative world that particular person is the most miserable, inferior and unwanted. He sees no use or meaning of his life, what so ever. There is no future for which he can live, no people whom they can count as their own friend or accomplish. The life for him becomes meaningless, and not worth living even for a second. It’s the whirlwind of robust negative emotion that paints the whole world dark on the canvas of his brain. It becomes an intense painful situation where the pain of harming own body becomes minimal, in fact that pain becomes a pleasurable event, a toll to escape all pervasive suffering. In that fit of negative emotion a person decides to end his life that his brain pictures as miserable, and unwanted by others around him.

For the other normal people, or brains for that matter, who are not in that state of whirlwind thinking, the act to commit suicide is illogical, irrational and cowardice. They would think how one can’t see the good things in life, future possibilities, happiness and instinct to live. However, many who would think in positive way have also gone through that negativity at times which creates the thought of suicide or even have successfully committed it.

The experts believe that suicide does not solve any problem rather it creates many other problems. It devastates the families and people close to the victim, fills with pain and intense felling of guild, anger and regrets that haunts them for many years. The patients who suffer from illness of brain should be constantly treated, monitored and counseled so that the web of negativity that their brain creates can be busted and their precious lives can be saved. Many lives have been saved by practicing these routines.

Forbidden Fruits of Aging Research !

The research on aging has been one of the ‘Hot Cake’ that researchers all over the world try to bake in their laboratories, and people in general try to sniff the aroma coming out of it, if not have the real bite.

Many leads on the aging research have come about in last few decades but their translation into clinics has eluded thus far. A couple of leads that I am going to discuss today are promising but have their own pros and cons.

The first approach is associated with telomere shortening. Telomere, discovered in 1970s, is the terminal part of the DNA in chromosomes, which protects the chromosomes from degradation. However, every time when a cell divides its DNA replicates.  Due to an inbuilt mechanism with every replication of DNA the length of telomere decreases, eventually exposing the terminal genes to be inactivated or degraded leading to aging and other related health problems.

A number of age-related diseases are associated with short telomeres like Alzheimer’s disease.

The length of telomeres shrink due to many reasons including very low levels of telomerase in most body cells, DNA replication mechanism itself and a variety of stresses that one has to face including emotional and environmental stress. Scientists have not found as yet the full proof solution to solve this problem.

Interestingly enough, I had discussed in my earlier write-up that somehow telomeres in a man's sperm tend to get longer with age, which means that his children will have longer telomeres to begin with and would live longer.

Scientists believe that if somehow the length of telomere is prevented from decreasing, the life of the cells and the individual with those cells could be extended. This is theoretically possible to achieve by activating an enzyme called telomerase that is known to extend the length of telomere.

However, practically increased telomere length and over active telomerase makes cells immortalized and cancerous. Consequently, question regarding which cells to be targeted when it comes to protecting the telomere length is a complicated one.

Another approach is the use of antioxidants to defy aging. Proponents of this approach believe that antioxidants may help slow aging and prevent a number of aging-related diseases.

From ancient times antioxidants have been advocated to have natural anti-aging properties. It is believed that anti-oxidants not only slow down the aging but also prevent many of the aging-related diseases.

Antioxidants are known to inhibit a transcription factor called nuclear factor kappa B (NF-kB), which synthesizes many inflammatory substances in body. Activated NF-kB has been implicated in diseases such as cancer, diabetic, cardiovascular, Alzheimer’s disease and other aging-related problems. It is thus understandable that inhibiting NF-kB would slow the aging process. A new research seems to further strengthen this claim.

Published in the journal Nature, a study in mice suggests that NF-kB becomes more active in the hypothalamus of mice as they get older. A mouse lives for nearly 1000 days on an average. When researchers blocked the activity of NF-kB, mice lived longer, roughly 1100 days. On the other hand, when they activated this factor in mice, they lived only 900 days or less.

Although natural antioxidants taken as fruits and vegetables have been found to lower the risk of some chronic aging-related diseases or aging itself, only a few clinical trials using antioxidants have shown anti-aging effects.

The synthetic antioxidants when taken have shown adverse effects. Since NF-kB also plays important role in the body’s immune response that fights against the bacterial and viral pathogens, its complete inhibition using specific inhibitor could be detrimental.

Although there is no direct study linking these two players in the aging process, it would be interesting to know whether antioxidants somehow prevent telomere shortening. A study that I came across suggests that telomeres are vulnerable to oxidative injury, and antioxidants may prevent it from further damage.

Having said that, it is obvious that antioxidants consumed as fruits and vegetables go a long way to protect from diseases and may also slow down aging process.

Thus, for the common man like us it is prudent to stick to our apples, berries, broccolis and carrots, and avoid antioxidant drugs that claim to retain your youth and slow your aging. They may rather pace it!!

A Clue to Solve Chemotherapy Drug Resistance in Pancreatic Cancer

Today I am going to discuss about an innovative thinking to solve a biological mystery when it comes to treating Cancers. One of my colleague and fellow student at Jawaharlal Nehru University, New Delhi, Dr Pankaj Singh, has come up with a landmark hypothesis to explain the resistance in some patients against a chemotherapy drug called Gemcitabine.

Dr Singh is one of the 14 scientists from the USA, who has recently won a $200,000 grant from the Pancreatic Cancer Action Network to work on his hypothesis.

Dr Singh, an Associate Professor at the Eppley Institute for Research in Cancer and Allied Diseases at University of Nebraska Medical Center, proposed that the cancer cells may be naturally producing a chemical, which competes with the drug Gemcitabine and leaves it ineffective.

Gemcitabine is an analog of one of the building blocks of DNA, cytidine. When inside the cell, the drug replaces the natural molecule cytidine in DNA and stops the DNA synthesis. In this way the cancer cells stop dividing and finally die.

A report of American Cancer Society's annual statistical report in 2009 attributed Cancer as the number one killer in America, surpassing the deaths due to heart diseases.

Among various types of cancers, pancreatic cancer is on rise. It is currently at fourth place in cancer related deaths, but poised to become second leading cause of cancer related death very soon, behind only to lung cancer, the number one cancer killer.

Unlike other cancers, the survival rate of pancreatic cancer patient is only 6 percent in the next five years post-diagnosis. Three out of four newly diagnosed patients die within a year of diagnosis. There are many famous victims of this disease.

The mean life span of a diagnosed person is at most six months. The reason for poor prognosis of pancreatic cancer is that the prospective patient remains symptom free leading to late diagnosis, and by the time the disease is diagnosed; in most cases it is already metastasized.

The disease is treated based on stage and location of the tumor and patients age. The tumor can be surgically removed at early stage. The most effective drug at the later stages is a chemotherapy drug called Gemcitabine, which is also used for treating cancers of lung, bladder and breast.

Unfortunately, many pancreatic cancer patients develop resistance to this drug.

The reason for developing the resistance has been troubling scientists, until Dr Pankaj Singh came up with his hypothesis. He thinks that it has to do with the way the cancer cells metabolize their sugars.

As per Dr Singh’s theory, pancreatic cancer cells make a lot of natural cytidine molecule themselves which outcompete the Gemcitabine leaving it useless as a chemotherapeutic drug. Further, he thinks that cancer cells burn the glucose, the main energy source for cells, at a higher rate.

The process of glucose break down in cells called glycolysis, and excessive glycolysis combined with lack of oxygen, common in tumor microenvironment, produces a lot of lactate. If you have felt muscle pain after strenuous exercise, it is because of lactate accumulation in the muscle. Dr Singh is also working to find if the increased lactate production due to increased glucose utilization by cancer cells is linked with the resistance to Gemcitabine.

By working on his innovative theories, Dr Singh is aiming to find a metabolic diagnostic biomarker that will help in deciding whether a patient will benefit from chemotherapy using this drug.

Since most of the patients have very little time left after diagnosis, this will help patients with targeted treatment and save many others from highly toxic and expensive chemotherapy.

Dad's Liver Fibrosis May Protect Son’s Liver

The liver is a vital organ in our body which performs many important functions, but sometimes gets inflamed because of various reasons including virus infection, and alcohol and drug abuse. A chronic inflammation of the liver results in fibrosis wherein healthy liver cells are replaced by collagen loaded fibrotic cells which compromise the structure and function of the liver. This course of disease is known for many years now, and there is nothing new in this.

source: www.hivandhepatitis.com

What is new however is that scientists have now discovered that fibrosis in father’s liver somehow results in the protection from this disease in his sons. The chronic liver injury because of either viral infection or alcohol abuse induces an epigenetic change in the sperm’s DNA. When this changed DNA is transmitted to the next generation it would protect the male progeny from liver fibrosis.

Epigenetic changes are modifications in the DNA caused by non-genetic and mostly lifestyle related exposures in ones’ life time. Although these changes do not seems to last and have limited effects on long-term evolutionary changes, sometimes epigenetic changes in the germ cells such as sperm can be transmitted to the next generation. Epigenetic changes are now implicated in many present day diseases including cancer and diabetes.  

The scientists, Müjdat Zeybel and his colleagues, reported that a long history of liver damage in rodents was related with transfer of adaptive epigenetic changes that suppressed liver fibrosis in first and 2^nd generation male rats.

The scientists induced liver fibrosis in rats by two different methods using carbon tetra-chloride and bile duct ligation. They found that prolonged lung injury resulted in the changes in rat sperm DNA which were inherited by the progeny. The male rats born from those sperms when tested by giving similar insults showed increased protection from liver fibrosis.

The main reason for this protection is higher amounts of a factor that prevent liver fibrosis, called peroxisome proliferator-activated receptor-gamma (PPAR-γ) in scientific term, in the liver of male pups that inherited modified DNA. They also had lower amounts of fibrosis promoting growth factor called Transforming growth factor-beta1, compared to those that inherited normal DNA.

The study published in Nature thus suggests that a history of liver fibrosis in male can protect their male progeny from such disease in next generation. But this protective adaptation was limited to liver and was not found to protect other organs, for example kidney, from fibrosis.

Although it remains to be determined how applicable these findings are in humans, this report should not result in believing that paternal liver injury would protect against the alcohol abuse-related liver diseases. We must therefore resist temptation to run to the bar with the logic to give protection to our future sons because many other genetic and environmental components are involved in liver diseases.

Vaccination against One Pathogen may protect others!

There has been debate and concerns regarding the annual flu vaccine here in USA, and people have been debating to get one or not get one.

Scientifically however, the case is in its favor. It has emerged out that vaccination created memory immune cells not only protect us from the pathogen against which vaccine was made, but also from other pathogens.

Scientists from Stanford University California have found that the T cells, a kind of immune cells, derived from healthy individuals recognized the HIV virus and responded to it as if they had seen the viral antigen before. This kind of response is expected from vaccinated or pre-infected individuals, but it is important to note that the blood donors in this study were neither vaccinated with HIV vaccine nor were ever infected, and they had tested negative for HIV.

T cells are a kind of white blood cells that carry CD4 antigens on them, and participate in launching immune response against a foreign pathogenic, viral or bacterial, proteins. The T cells, also called memory cells, are made when a bacterial or viral protein is present in the body either due to vaccination or some kind of infection.

In the people infected from HIV virus, the T-cells lose the capacity to launch an immune attack, and infetced person develops the condition called Acquired Immune Deficiency Syndrome or AIDS. Such patients are thus likely to get other infections rather easily due to weakened immunity.

On the contrary when the scientists tested the umbilical cord blood from the new born, who had never ‘seen’ a foreign protein, they found no signs of any memory T cells. It explains why infants and younger children are more prone to catch infections, thus need vaccination.

The scientist also found that T cells from flu vaccinated people were able to recognize the antigens from other bacterial species other than from flu. They believe that this is possible by cross-reactivity to varied antigens and it may be a major mechanism in making populations of memory T cells for infectious diseases that an individual has not yet developed.

This study thus proposes to explain how vaccination against one disease may protect from other diseases as well. The study also signifies the influence of pathogen-rich versus hygienic environments in developing immunity to new pathogens that may impact child and adult health.