Metformin helps dieting teens to lose weight....

We know that Metformin  (see structure), is a  biguanide hypoglycemic  agent used in the treatment of non-insulin-dependent diabetes mellitus not responding to dietary modification. Metformin improves glycemic control by improving insulin sensitivity and decreasing intestinal absorption of glucose. Metformin's pharmacologic mechanisms of action are different from other classes of oral antihyperglycemic agents. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose and improves insulin sensitivity by increasing peripheral glucose uptake and utilization. In my earlier blogs, I have covered the recent (findings)  updates on metformin.

Now researchers  lead by Dr. Darrell Wilson (from Division of Pediatric Endocrinology and Diabetes, Stanford University)  have found that metformin appears to help overweight teenagers lose weight when combined with a program designed to help them change their lifestyle habits.

As per the claim by the authors though metformin hydrochloride is  used as a primary or adjunctive treatment in obese  nondiabetic adolescents there are limited short-term data to support this therapy  and also it is unclear whether any observed effects of metformin on body mass index. Therefore  the researchers conducted a 48-week randomized, double-blind, placebo-controlled trial of extended-release (XR) metformin therapy in nondiabetic obese adolescents  followed by a 48-week monitoring period after completion of treatment.

Researchers found that the addition of metformin to a lifestyle change intervention for a period of 12 months resulted in a significant improvement of BMI regardless of baseline fasting insulin levels, that persisted for 12 to 24 weeks after cessation of drug treatment. The mean (SE) reduction in BMI of –1.1 (0.5) at 1 year was comparable with that observed in other randomized controlled trials of metformin treatment in obese adolescents, although these randomized controlled trials involved shorter treatment duration (about 6 months), targeted obese children with additional diabetes risks, and had smaller sample sizes.

The mechanisms of action for these effects have not fully been elucidated but may involve beneficial effects on carbohydrate and lipid metabolism, mediated through adenosine monophosphate kinase.

Researchers conclude that  "metformin  in combination with lifestyle modification, had a small but statistically significant effect to reduce BMI in obese adolescents; this effect waned within 12 to 24 weeks of discontinuing metformin treatment". These results indicate that metformin may have an important role in the treatment of adolescent obesity. Longer-term studies will be needed to define the effects of metformin treatment on obesity-related disease risk in this population....

Ref : http://archpedi.ama-assn.org/cgi/content/full/164/2/116?home

7,8-Dihydroxyflavone (a selective TrkB agonist) as new class of brain protecting drugs ?

In recent days, I have seen many groups working on the diverse activities of  flavonoid family of chemicals. In my earlier blog, have mentioned about Quercetin   (quercetin a flavonoid has been reported for diverse activities). Now interestingly  investigators at Emory University School of Medicine,  have reported that '7,8-Dihydroxyflavone' (see structure - also a  member of the flavonoid family of chemicals, abundant in fruits and vegetables-cherries to soybeans)   can partially prevent the death of neurons in experimental models of three neurological diseases" and  this  selective effect suggest that it could be  a new class of brain-protecting drugs.

Investigators at Emory University School of Medicine, led by Dr. Keqiang Ye, (Associate professor of pathology and laboratory medicine), were searching for a way to mimic a protein found in the brain called BDNF (brain-derived neurotrophic factor).

BDNF has been studied extensively for its ability to protect neurons vulnerable to degeneration in several diseases, such as ALS, Parkinson's and Alzheimer's disease,  Ye, one of the authors says, "the trouble with BDNF is one of delivery. It's a protein, so it can't cross the blood-brain barrier and degrades quickly". 

Researchers tried a a library of chemicals to find those that could stimulate one of the proteins on the surfaces of neurons that BDNF binds to. They could show that, 7,8-dihydroxyflavone sends survival signals to brain cells by pulling together two TrkB receiver-dish molecules, just like BDNF does. Interesting part of this research is that, 7,8-Dihydroxyflavone is active in the brain when injected into the body cavity (meaning that it can cross the blood-brain barrier). As claimed by the co-author Ye, many experimental "neuroprotectant" drugs have been unsuccessful in clinical trials for diseases such as stroke and Parkinson's over the last decade and 7,8-Dihydroxyflavone is the first molecule that specifically triggers TrkB. To show the effects of 7,8-dihydroxyflavone depended on TrkB,  authors used mice with a modified TrkB gene and were successful in doing so. Detailed animal studies to substantiate the claim  are essential , still  in my opinion its a good achievement... (details...)

FDAs approval of Lapatinib in combination with Letrozole to treat breast cancer...

In my earlier blog, I mentioned about the combination of Lapatinib and Trastuzumab for breast cancer treatment. Now FDA has  approved Lapatinib in combination with Letrozole (see structure ; Letrozole trade name Femara, an oral non-steroidal aromatase inhibitor for the treatment of hormonally-responsive breast cancer after surgery)  to treat hormone positive and HER2-positive advanced breast cancer in postmenopausal women for whom hormonal therapy is indicated. This drug combination of  Lapatinib  & Letrozole provides women being treated for advanced breast cancer with an important treatment option. 

The entirely oral treatment regimen works by targeting both HER2 and the hormone receptors, thereby slowing the cancer cells' ability to grow or spread. As per the claim by  Dr. Richard Pazdur, (Director, Office of Oncology Drug Products, FDA's Center for Drug Evaluation and Research) women with HER2-positive disease receiving the Lapatinib plus Letrozole combination more than doubled the time they lived without the cancer progressing compared with those receiving Letrozole alone (35 weeks vs. 13 weeks).

Lapatinib, was initially approved in combination with a chemotherapy drug, Xeloda (capecitabine) in 2007. This combination was used to treat women with advanced breast cancer tumors with the HER2 protein who had received prior treatment with chemotherapy drugs, including an anthracycline and a taxane, and Herceptin (trastuzumab), an anti-cancer antibody used to treat HER2-positive advanced breast cancer. Safety information from this study was consistent with previous Lapatinib clinical studies in advanced breast cancer. The most commonly reported side effects of the combination were diarrhea, rash, nausea and fatigue. Still clinical trials are to be carried out, in my opinion its a good achievement...

Ref : http://www.prnewswire.com/news-releases/fda-expands-use-of-approved-breast-cancer-drug-83072502.html

Green tea might help to treat Uterine Fibroids....

In continuation of my update on green tea   (pic : source : greenteatruth.org ).......  

We have seen many research groups  trying to explore the  usefulness of  green tea for reduction in heart disease (bad cholesterol),  increase in metabolic rate (fat oxidization) prevention  of Alzheimer’s or Parkinson’s diseases, lowering incidence of cancers and  weight reduction.

 Now researchers from Meharry Medical College in Nashville, Tenn lead  Dr. Ayman Al-Hendy ,   have found that green tea extract shows promise as a treatment for uterine fibroids. The key ingredient responsible for this activity is  "epigallocatechin gallate (EGCG)". The researchers investigated  the effect of epigallocatechin gallate  on rat leiomyoma (ELT3) cells in vitro and in a nude mice model. ELT3 cells were treated with various concentrations of EGCG. Cell proliferation, proliferation cell nuclear antigen (PCNA), and cyclin-dependent kinase 4 (Cdk4) protein levels were evaluated. As per the claim by the researchers, EGCG significantly decreased PCNA and Cdk4 protein levels. The authotrs conclude that EGCG effectively inhibits proliferation and induces apoptosis in rat ELT3 uterine leiomyoma cells in vitro and in vivo.

Ref : http://www.ajog.org/article/S0002-9378%2809%2902102-4/fulltext

Pomegranate extract (β-Sitosterol) stimulates uterine contractions.........

In continuation of my update on pomegranate and its importance in the diet, I found this info interesting to share with...

Earlier studies have suggested that the pomegranate’s antioxidant and anti-inflammatory properties have a positive impact on health. Scientists at the University of Liverpool   and the Suranaree University of Technology, Thailand, wanted to understand its effect on uterine contractions to explore new ways of treating women who may experience difficult labours.  Currently the only available drug to treat women with a poorly contracting uterus is oxytocin, a hormone which only works approximately 50% of the time,  so there is need of a good  drug.

The team identified   β-Sitosterol,   which inhibit the absorption of cholesterol in the intestine  (as the main constituent of pomegranate seed extract) could be used as a natural stimulant to encourage the uterus to contract during  labour.

        I would say this activity (stimulation of  uterine contractions) is an interesting out come from the research group, because β-Sitosterol has been (earlier) reported ;

a) in treatment of hypercholesterolemia;
b) to possess  anticancer activity (prostate & breast);
c) in a small study, it shows a positive effect on male hair loss in combination with Saw palmetto.

Researchers,  also found that β-Sitosterol concentration  is more in the  pomegranate seed extract  rather  than pomegranate juice itself  and by adding this seed extract to the uterus tissue samples from animals they found that the muscle cells increased their activity. 

The reason for this activity,  (as claimed by the researchers) is due to a rise in calcium, which is necessary in order for any muscle to contract (which is usually affected by hormones, nerve impulses and some drug treatments) . So further studies  like how β-Sitosterol  in pomegranate extract could increase calcium are essential and might lead to  an interesting step towards identifying new ways of treating dysfunctional labour ..more..

Pazopanib for the treatment of advanced renal cell carcinoma.......

In continuation of my update on Pazopanib, I found this interesting info. In my earlier blog , I mentioned that lots of research groups are trying the same drug for other forms of cancer.  Dr. Cora Sternberg and co authors (Chief of the medical oncology department at the San Camillo and Forlanini Hospital in Rome, Italy), have come up with interesting results from a phase 3 study included 233 patients with previously untreated kidney cancer (also known as renal cell carcinoma) that was locally advanced or had spread, and 202 patients with renal cell carcinoma who had previously been treated with cytokine therapy (interferon or interleukin). The patients were randomly assigned to take pazopanib tablets (290 patients) or a placebo drug (145 patients).

As per the claim by the authors, in the pazopanib group, it took an average 9.2 months for the cancer to progress, vs. an average 4.2 months in the placebo group. The difference was greatest in previously untreated patients (11.1 months for the pazopanib group and 2.8 months for the placebo group), but also was found among patients previously treated with cytokines (7.4 months in the pazopanib group vs. 4.2 months in placebo group). 

Common side effects of pazopanib treatment included diarrhea (52 percent), high blood pressure (40 percent), hair color changes (38 percent), nausea (26 percent), weight loss (22 percent) and vomiting (21 percent).

Ref : http://jco.ascopubs.org/cgi/content/abstract/JCO.2009.23.9764v1 

FDA approves Liraglutide for Type 2 Diabetes, with a warning.....

Liraglutide, marketed under the brand name Victoza, is a long-acting glucagon-like peptide-1 (GLP-1) analog that has been developed by Novo Nordisk for the treatment of type 2 diabetes. The product was approved by the European Medicines Agency (EMEA) on July 3, 2009, Now the same drug has been approved  by the FDA.

The interesting part of this approval lies in the fact that, Liraglutide was reviewed by an FDA advisory panel which expressed serious concerns that the drug may cause thyroid tumors. Whereas based on the studies and consistent with the relevant literature it is obvious that the rodent C-cell tumors induced by dosing of liraglutide were caused by a non-genotoxic, specific receptormediated mechanism to which rodents are particularly sensitive whereas non-human primates and humans are not. Liraglutide improves control of blood glucose.  It reduces meal-related hyperglycaemia (for 12 hours after administration) by increasing insulin secretion, delaying gastric emptying, and suppressing prandial glucagon secretion.

As per the claim by the company, the advantages are:

a) acts in a glucose-dependent manner, and  stimulate insulin secretion only when blood glucose levels are

    higher than normal. Consequently, it shows negligible risk of hypoglycemia;

b) has the potential for inhibiting apoptosis and stimulating regeneration of beta cells;

c) decreases appetite and maintains body weight, as shown in a head-to-head study versus glimepiride;

d) lowers blood triglyceride levels and only mild and transient side effects, mainly gastrointestinal &
e) has a half-life after subcutaneous injection of 11–15 hours and hence once-daily GLP-1 derivative.

But the FDA, warned that the once-daily injection shouldn't be used as an initial (first-line) treatment until additional studies are completed, since the drug may cause thyroid tumors or a rare disease called medullary thyroid cancer. People at risk for this type of cancer shouldn't use the drug, the FDA stressed. Hope the further studies will rule out the possibility of the drug causing thyroid tumors..

For details, one can read the press release....

Levoleucovorin's supplemental New Drug Application (sNDA) for colorectal cancer...

We know that  Levoleucovorin (see structure; source : chemspider) is  used to treat or prevent toxic effects of methotrexate in people who have received methotrexate to treat bone cancer.

Recently, Spectrum Pharmaceuticals announced that it has met with the FDA regarding it’s supplemental New Drug Application (sNDA) for FUSILEV^® (levoleucovorin) for injection for the treatment of patients with advanced metastatic colorectal cancer. The company is expected to  to submit in the third quarter of 2010. The FDA did not request any additional efficacy studies. Hope the FDA will  approve the drug  for advanced metastatic colorectal cancer...

Ref  : http://investor.spectrumpharm.com/releasedetail.cfm?ReleaseID=439605

Rapamycin as a potential treatment for kidney disease (ADPKD).........

I did  mention about the use of Rapamycin (see structure)  to improve the  efficacy of tuberculosis vaccine in my earlier blog. This drug has been already  used as an immunosuppressant drug to prevent rejection in organ transplantation,  especially useful in kidney transplants.

 Rapamycin, was originally developed as an antifungal agent. However, this was abandoned when it was discovered that it had potent immunosuppressive and antiproliferative properties. Some researchers have  also reported that  the drug prolong the life of mice and might also be useful in the treatment of certain cancers.

Researchers from UC Santa Barbara  earlier claimed that, rapamycin has  a potential to treat  kidney disease,  however  concluded  that the  mice had different genes affected than human patients. Interestingly, the same researchers recently found that  "rapamycin is also highly effective in a new mouse model in which the same gene is affected as in most human patients".

As claimed by the lead researcher, Thomas Weimbs currently, no treatment exists to prevent or slow cyst formation and most ADPKD patients require kidney transplants or lifelong dialysis for survival. I think this will boost the confidence of the several international groups,  who are undertaking the  clinical trials  to test the safety and efficacy of rapamycin and related drugs in polycystic kidney disease. Though the  researchers are hopeful of positive results  they caution that,  it will be critical to balance any benefits against the expected side effects to judge whether these drugs should be recommended for the treatment of polycystic kidney disease. Let us be optimistic.....

Ref : http://www.ia.ucsb.edu/pa/display.aspx?pkey=2164

Positive results from Phase 2 trial of picoplatin for colorectal cancer...

In continuation of my update on picoplatin,.......

Poniard Pharmaceuticals, Inc,  claims that Phase 2 trial  study met its primary objective, that is picoplatin in combination with 5-fluorouracil and leucovorin (FOLPI regimen) was associated with a statistically significant reduction in neurotoxicity (p <0.004) compared to oxaliplatin given in combination with 5-fluorouracil and leucovorin (FOLFOX regimen). More...

FDAs approval of fampridine-SR for multiple sclerosis...

In continuation of my  update on MS, I found this info useful to share with. Multiple sclerosis (MS, also also known as disseminated sclerosis or encephalomyelitis disseminata) is a disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms. Disease onset usually occurs in young adults, and it is more common in females. MS affects the ability of nerve cells in the brain and spinal cord to communicate with each other. Nerve cells communicate by sending electrical signals called action potentials down long fibers called axons, which are wrapped in an insulating substance called myelin.

In MS, the body's own immune system attacks and damages the myelin. When myelin is lost, the axons can no longer effectively conduct signals. The name multiple sclerosis refers to scars (scleroses, better known as plaques or lesions) in the white matter of the brain and spinal cord, which is mainly composed of myelin. (see, picture, source : URMC).

Now FDA has approved fampridine-SR (see structure, source : chemspider),  for the treatment of multiple sclerosis. Most interesting part of the research lies in the fact that Researchers at the University of Rochester Medical Center (URMC) have been evaluating the effects of the drug in MS for more than 10 years- it is the first medication shown to enhance some neurological functions in people with the disease and I think their efforts helped pave the way for action by the FDA.

Researchers at URMC helped develop the study protocols and lead the clinical trials  that demonstrated consistently improved mobility - timed walking speed- in more than a third of patients with MS. This is the first instance in which a drug for multiple sclerosis was found to improve function lost as a result of the disease. Goodman and his colleagues published the results of a Phase 3 clinical trial of the drug in the journal Lancet. Fampridine-SR is being developed by Acorda Therapeutics and marketed under the name Ampyra. The company submitted a new drug application to the FDA in February 2009. An expert advisory panel recommended approval of the drug in October and that recommendation was adopted by the FDA on 23. January 2010.

As per the claim by the researchers, fampridine improves the transmission of signals in the central nervous system of some multiple sclerosis patients by blocking potassium ion channels in nerve cells and restoring signal conduction( have covered an article in the same lines).

The authors claim that, 35% of patients taking the drug were responders who consistently improved their walking speed by an average of about 25%. While walking was the primary measure, patients also reported that they could walk farther distances, climb stairs better, and stay on their feet longer. Except for the mild seizure, at the FDA approved dosage, the drug is safe. Hope, people with MS will have some sort of relief......

Ref : http://www.urmc.rochester.edu/news/story/index.cfm?id=2744

Naproxcinod a better NSAID.....

I knew  about Naproxen, because my first job was with Rallis India  Limited and the pharma division (sold to Shreya Group) was selling it as  a gel. It works by inhibiting both the COX-1 and COX-2 enzymes and that is the reason, why it has side effects. It has  been established already that the selective inhibitors of  COX-2 & 5 -LO will be the best drugs with least or no ulcerogenecity. We have  some drug like Celecoxib with selective inhibition of COX-2 (cyclo oxygenase enzyme), still we need to have selective inhibitors of both COX-2 & 5 -LO, so that  there will not be any cases like Rofecoxib withdrawal.

Naproxcinod, is a nitroxybutyl ester of naproxen. The ester group allow it to also act as a nitric oxide donor. Interestingly, this second mechanism of action makes naproxcinod the first of a new class of drugs, the cyclooxygenase inhibiting nitric oxide donators (CINODs), that are expected to produce similar analgesic efficacy to traditional NSAIDs, but with less gastrointestinal and cardiovascular side effects.  Now NicOx S.A announced that European Medicines Agency (EMEA) has validated the Marketing Authorization Application (MAA) for naproxcinod. NicOx is seeking approval for an indication for the relief of the signs and symptoms of primary osteoarthritis. This follows the acceptance for filing of a New Drug Application (NDA) by the US Food and Drug Administration (FDA) in November 2009.

More interestingly, in addition to naproxcinod, NicOx's pipeline includes several nitric oxide- donating NCEs, which are in development internally and with partners, including Merck & Co., Inc., for the treatment of widespread eye diseases, cardiometabolic diseases, hypertension and dermatological disease.

Details of the press release, one can read at the link....

LOAD - a better combination therapy against Helicobater pylori....

In continuation of my update on Helicobater pylori infection and its treatment, I found this info interesting to share with. Dr. Patrick Basu and his colleagues at Columbia University College of Physicians and Surgeons found that,  a shorter course of the four-drug combination (LOAD), seven days vs. a ten-day treatment, is equally effective. As per the claim by the researchers  Helicobater pylori, a bacteria implicated in peptic ulcers and gastritis, was eradicated in 95 percent patients who took a 7-day course of combination therapy with  levofloxacin (L), omeprazole (O), nitazoxanide (Alinia®) (A) and doxycycline  (D) (LOAD) compared to eradication in only 80.9 percent of patients on lansoprazole, amoxicillin and clarithromycin (LAC) for seven days.

The study included 135 patients with treatment naïve Helicobacter pylori infection, who were randomized to LOAD (7 or 10 days) vs. LAC (10 days). There was a total wash out period of six weeks from any prior antibiotic and PPI use prior to the initiation of therapy.

Ref : http://www.acg.gi.org/media/releases/09ACGReleaseLOADTherapyforHPylori.pdf

SPC3649 ( LNA- locked nucleic acid) - a new hope for hepatitis C.....

When  I was working with Innovasynth Technologies, Khopoli, I had an opportunity to do literature survey about  Lock Nucleic Acids (LNAs) and Peptide Nucleic Acids (PNAs) (we were supposed to work on the preparation of  some of the LNAs & PNAs for US based companies). In my opinion though these class of compounds (including oligonucleotides) are  still emerging,  I think in the days to come there will be more and more drugs from oligonucleotides, Locked Nucleic Acids (LNAs) and Peptide Nucleic Acids, (PNAs) class of compounds.

LNAs : A locked nucleic acid (LNA) (see the right side general structure), is a modified RNA nucleotide. Ribose moiety of an LNA nucleotide is modified with an extra bridge

connecting the 2' oxygen and 4' carbon. The bridge "locks" the ribose  in the 3'-endo (North) conformation, which is often found in the A-form of DNA or RNA. LNA nucleotides can be mixed with DNA or RNA bases in the oligonucleotide whenever desired. This locking  significantly increases the thermal stability (mp) of oligonucleotide.

LNA nucleotides are used to increase the sensitivity and specificity of expression in DNA microarrays, FISH probes, real-time PCR probes and other molecular biology techniques based on oligonucleotides. For the in situ detection of miRNA the use of LNA is currently the only efficient method. A triplet of LNA nucleotides surrounding a single-base mismatch site maximizes LNA probe specificity unless the probe contains the  G-T mismatch. We have already seen some antisense drugs (oligonucleotides from Geron & Isis) and some are into clinical trials.

Now its interesting to see that Santaris Pharma   is currently advancing LNA based compounds within infectious diseases, metabolic disorders, oncology, inflammatory and rare genetic disorders.

Santaris Pharama, has developed a LNA,  SPC3649 - which captures a small RNA molecule in the liver, called microRNA122, that is required for HCV replication.

As per the claim by the company, SPC3649 works by altering the environment in the host liver cell to inhibit viral replication rather than inhibiting the virus itself. This subtle difference (in comparison  with other therapies) may have significant implications, as it may reduce the risk of the virus becoming resistant to therapy – a major concern with current therapies.

As per the claim by Dr. Robert Lanford,  (who has collaboration with Santaris Pharma), that in a preclinical study  SPC3649 successfully inhibited miR-122, a liver-expressed microRNA important for Hepatitis C viral replication. By inhibiting miR-122, SPC3649 dramatically reduced Hepatitis C virus in the liver and in the bloodstream in chimpanzees chronically infected with the Hepatitis C virus. Four HCV chronically infected chimpanzees were treated weekly with 5 or 1 mg/kg of SPC3649 for 12 weeks followed by a treatment free period of 17 weeks. The two animals that received the 5 mg/kg dose had a significant decline in viral levels in the blood and liver of approximately 2.5 orders of magnitude or approximately 350 fold. Hope the new therapy could potentially replace interferon (interferon and ribavirin is  approved by FDA for hepatitis C and this treatment is very toxic, requires 48 weeks with 50% success) in future cocktails, since it provides a high barrier to resistance. This antiviral could be used alone to treat disease progression and there are indications that it can convert interferon non-responders to responders, so that non-responders to the current therapy could be treated with the combination of this drug with interferon.   More....

Those interested  can see the video demo with the link

Apple pectin as a novel prebiotic substance, that helps the intestinal microbiota....

We know the proverb "An apple a day keeps the doctor away" because of the fact that apple has been  addressing the health effects of the fruit, dates from 19th century. Interestingly apples have shown reduce the risk of  colon cancer, prostate cancer and lung cancer.Compared to many other fruits and vegetables, apples contain relatively low amounts of Vitamin C, but are rich source of other antioxidants.  The fiber content, while less than in most other fruits, helps regulate bowel movements and may thus reduce the risk of colon cancer. They may also help with heart disease, weight loss,  and controlling cholesterol, as they do not have any cholesterol, have fiber, which reduces cholesterol by preventing re absorption, and are bulky for their caloric content like most fruits and vegetables . There is  in vitro evidence that  phenolic compounds in apples (quercetin, epicatechin, and procyanidin B2) are  cancer-protective and  also demonstrate antioxidant activity.

Apples can be canned or juiced and the juice can be fermented to make apple cider (non-alcoholic, sweet cider) and cider (alcoholic, hard cider), ciderkin, and vinegar. Alcoholic beverages are produced such as applejack (beverage) and Calvados.  Apple wine can also be made. Pectin is also produced. 

Now microbiologists at the University of Denmark's National Food Institute,  tested the effect of apple consumption by feeding rats a diet of whole apples as well as apple-derived products such as apple juice and puree. The researchers then checked the bacteria in the guts of the rats to see if consuming apples affected levels of "friendly" bacteria, which are beneficial for digestive health and may reduce the risk of some diseases. Researchers found that rats eating a diet high in pectin, a component of dietary fiber in apples, had increased amounts of certain bacteria that may improve intestinal health.

As per the claim by the researchers, consuming apples affected levels of "friendly" bacteria, (bacteria that are beneficial for digestive health) and there by  reduce the risk of some diseases. And bacteria help produce short-chain fatty acids that provide ideal pH conditions for ensuring a beneficial balance of microorganisms. They also produce butyrate, which is an important fuel for the cells of the intestinal wall. Interestingly, consumption of apple pectin (7% in the diet) increases the population of butyrate and beta-glucuronidase producing Clostridiales, and decreases the population of specific species within the Bacteroidetes group in the rat gut. Similar changes were not caused by consumption of whole apples, apple juice, puree or pomace....

Ref : http://www.biomedcentral.com/content/pdf/1471-2180-10-13.pdf