The Coliform Kind: E. coli and Its “Cousins” The Good, the Bad, and the Deadly

Even though some intestinal bacteria strains are pathogenic and even deadly, most coliforms strains still show evidence of being one of God’s “very good” creations. In fact, bacteria serve an intrinsic role in the colon of the human body. These bacteria aid in the early development of the immune system and stimulate up to 80% of immune cells in adults. In addition, digestive enzymes, Vitamins K and B12, are produced byEscherichia coli and other coliforms. E. coli is the best-known bacteria that is classified as coliforms. The term “coliform” name was historically attributed due to the “Bacillus coli-like” forms. The bacteria are characteristically Gram-negative bacillus (rod-shaped) organisms found in the colons of man and animal. Typical genera include Escherichia, Citrobacter, Klebsiella, and Enterobacter. All these bacteria genera ferment lactose and are phenotypically similar. These genera are often used as indicators in testing the quality of water. Their presence indicates contamination that can cause transmission of infection. This leads to a bad reputation for the coliform kind. How could God consider this creation good if they cause disease

Molecular Determinants of Fetal Tolerance and the Transition to Adult Immunity

The perinatal immune system is highly tolerogenic and is phenotypically and functionally distinct from the adult immune system. This tolerogenic nature is a double-edged sword for newborns. While it is beneficial to prevent excessive inflammation against the vast array of foreign antigens encountered after birth, it also causes a lack of immune responses to life-threatening infections. My dissertation research aims to investigate the mechanisms by which perinatal T cells contribute to immune tolerance in infants. A deeper understanding of the nature of the perinatal immune system will provide pivotal knowledge to develop safe and effective strategies to protect infants from infection and to establish immune homeostasis with commensal microbes. Using umbilical cord blood (UCB) T cells as a model to study perinatal immunity, we found that antigen receptor stimulation of T cells in UCB leads to the development of Foxp3+ T cells in both CD4+ and CD8+ T cell subsets. These UCB-derived Foxp3+ T cells are phenotypically and epigenetically distinct from canonical thymus-derived Tregs (tTregs) in adults, but they carry immune regulatory functions in vitro and in vivo. The development of Foxp3+ T cells requires CD36hi monocytes. Adult blood contains a group of lymphocytes that inhibits monocyte-induced Foxp3+ T cell development, showing how perinatal blood differs from adult blood. Foxp3+ T cell development also requires IL-2. Alcohol, which is known to cause immunological defects, reduces the expression of CD25, a component of the high affinity IL-2 receptor, and blocks Foxp3+ T cell development. The result suggests that immunological dysfunctions found among infants born from alcoholic mothers may be in part due to the impaired development of these Foxp3+ T cells during their fetal life. To further elucidate the mechanisms that contribute to perinatal immunological tolerance, we investigated the expression of Helios, another transcription factor known to be expressed by tTregs along with Foxp3. We found that Helios is expressed significantly more frequently by UCB and neonatal peripheral blood T cells than adult T cells. Similar results were observed in mice. The expression frequency decreased rapidly after birth. The data suggested that T cells from fetal/perinatal origin express Helios. Indeed, we found that most gut-associated T cells, which are known to originate from the fetal thymus, express Helios in the fetus and maintained Helios expression throughout adulthood. Additionally, human T cells that matured in mice that received UCB hematopoietic stem cells also express Helios. Gene knockout of Helios in UCB T cells showed a significant increase in expression of multiple effector cytokines, suggesting that one of Helios\u27 functions is to suppress effector cytokine production by activated T cells. Together, these data demonstrated multiple mechanisms by which T cells can contribute to immune tolerance in neonates. First, the perinatal peripheral environment promotes T cells to differentiate into a unique group of Foxp3+ T cells that carry suppressive functions. Second, perinatal T cells express high levels of Helios, which suppress activated T cells to produce effector cytokines. Together, both intrinsic (Helios) and extrinsic (CD36hi monocytes) mechanisms promote the tolerogenic nature of the perinatal immune system

Beneficial impacts of goat milk on the nutritional status and general well-being of human beings: Anecdotal evidence

Goats provide an essential food supply in the form of milk and meat. Goat milk has distinct qualities, but it shares many similarities with human and bovine milk regarding its nutritional and therapeutic benefits. Because of their different compositions, goat and cow milk products could have different tastes, nutrients, and medicinal effects. Modification in composition aid of goat milk determining the viability of goat milk processing methods. Comparatively, goat's milk has higher calcium, magnesium, and phosphorus levels than cow's or human milk but lower vitamin D, B12, and folate levels. Goat milk is safe and healthy for infants, the old, and healing ailments. Capric, caprylic, and capric acid are three fatty acids that have shown promise as potential treatments for various medical issues. Considering the benefits and drawbacks of goat milk over cow milk is essential; goat milk is more digestible, has unique alkalinity, has a better buffering capacity, and has certain medicinal benefits. Acidifying goat milk shrinks fat globules and makes protein friable (with less αs1-casein and more αs2-casein). Goat milk treats malabsorption illnesses because it has more short- and medium-chain triglycerides that give developing children energy. In wealthy countries, goat milk and its products—yoghurt, cheeses, and powdered goods—are popular with connoisseurs and persons with allergies and gastrointestinal issues who need alternative dairy products. A food product category containing fermented goat milk with live probiotic microbes appears promising nutritionally and medicinally. This article presents anecdotal evidence of the therapeutic effects of consuming goat milk for human health and its nutritional value

Prediction Of Feeding Difficulties In Post-Operative Neonates

The purpose of this study was to determine whether feeding difficulties in post-operative neonates correlate with intraoperative findings. A retrospective study of neonates undergoing gastrointestinal surgery between January 2002 and December 2005 was performed. Operative notes were used to classify infants into four groups based on post-operative anatomy and anticipated intestinal function: class 1: anatomically normal/normal function (n=22); class 2: anatomically normal/dysfunction (n=21); class 3: anatomically short/normal function (n=31); and class 4: anatomically short/dysfunction (n=21). Class 3 was further divided into two subgroups based on ostomy location: proximal ostomy (class 3a, n=11) vs. distal ileostomy (class 3b, n=21). Anatomically short was defined as loss of \u3e50% of small bowel or high ostomy. Dysfunction was defined as decreased motility or absorptive capacity of the small bowel due to dilation, inflammation, or ischemia. Data were collected from the first day of enteral feeding until the infant reached full feeds or was discharged. Outcomes included: time to 50% and to full enteral feeds, days on TPN/lipids, and episodes of feeding intolerance (large aspirates, emesis) or malabsorption (increased volume or watery consistency of stools). Statistical analyses were performed using Kruskal-Wallis test for continuous variables and chi-square test for dichotomous variables. We enrolled 95 patients. Time to full feeds was longer in anatomically short infants (class 3a and 4) than in anatomically normal infants (class 1 and 2, p\u3c0.05). The same trend was seen in median days of exposure to TPN and lipids. Class 3b infants behaved more like anatomically normal infants despite having an ileostomy. Feeding intolerance occurred in 81% and 71% of infants in classes 2 and 4 respectively, which was significantly higher than in classes 1 (5%), 3a (55%), and 3b (30%), all p\u3c0.05. The median days of feeding interruption due to intolerance were significantly higher in classes 2 and 4 (p\u3c0.05). Malabsorption affected 62% and 64% of patients in classes 3a and 4, respectively, which was significantly higher than in classes 1 (5%), 2 (19%) or 3b (20%), all p\u3c0.05. The median days of feeding interruption due to malabsorption were significantly higher in classes 3a and 4 (p\u3c0.05). These data demonstrate that surgeon-described post-operative anatomy and anticipated gastrointestinal function correlate with feeding difficulties in the post-operative period. We also found that infants with a distal ileostomy behave similarly to those who are anatomically normal, indicating feedings for these infants can likely be advanced more quickly. Feeding guidelines based on this classification system should be evaluated prospectively

Therapeutic Microbiology: The Role of Bifidobacterium breve as Food Supplement for the Prevention/Treatment of Paediatric Diseases

The human intestinal microbiota, establishing a symbiotic relationship with the host, plays a significant role for human health. It is also well known that a disease status is frequently characterized by a dysbiotic condition of the gut microbiota. A probiotic treatment can represent an alternative therapy for enteric disorders and human pathologies not apparently linked to the gastrointestinal tract. Among bifidobacteria, strains of the species Bifidobacterium breve are widely used in paediatrics. B. breve is the dominant species in the gut of breast-fed infants and it has also been isolated from human milk. It has antimicrobial activity against human pathogens, it does not possess transmissible antibiotic resistance traits, it is not cytotoxic and it has immuno-stimulating abilities. This review describes the applications of B. breve strains mainly for the prevention/treatment of paediatric pathologies. The target pathologies range from widespread gut diseases, including diarrhoea and infant colics, to celiac disease, obesity, allergic and neurological disorders. Moreover, B. breve strains are used for the prevention of side infections in preterm newborns and during antibiotic treatments or chemotherapy. With this documentation, we hope to increase knowledge on this species to boost the interest in the emerging discipline known as "therapeutic microbiology"

Präbiotikasupplementation Schwangerer und ihre Wirkung auf die mütterliche und kindliche Darmflora sowie auf ausgewählte fetale Immunparameter - eine randomisierte, doppelblinde, placebo-kontrollierte Pilotstudie

Diese Studie ist die erste, randomisierte, doppel-blinde, placebo-kontrollierte Langzeitpilotstudie, welche die Wirkung der Präbiotika-Supplementation während der Schwangerschaft auf die Zusammensetzung der mütterlichen und kindlichen Darmmikroflora untersucht. Die Präbiotika-Supplementation im letzten Trimenon der Schwangerschaft zeigte eine gute Verträglichkeit und einen bifidogenen Effekt auf die Darmflora Schwangerer. Im Gegensatz dazu, hatte die Präbiotika-Supplementation keinen signifikanten Einfluss auf die Anzahl der Lactobazillen (Bakterien/mL) oder deren prozentualen Anteil an der Gesamtdarmmirkoflora. Ein Einfluss auf die mütterliche Stuhlfrequenz bzw. Konsistenz und auf die vaginalen pH-Werte war nicht nachweisbar. Die Präbiotika- und die Placebo-Supplementierten Gruppen unterschieden sich nicht bezüglich der neonatalen Entwicklung der Bifidobakterien- und Lactobazillen-Microflora sowie der untersuchten Nabelschnurparameter. Aus den vorliegenden Daten schließen wir, dass die mütterliche Präbiotika-Supplementation nicht zur Induktion eines bifidogenen Effekts in der Darmflora gestillter Kinder empfohlen werden kann. Es ist anzunehmen, dass eine Erhöhung der Bifidobakterien im Neugeborenendarm effektiver durch die direkte Supplementation der Babynahrung mit Präbioitika erreicht werden kann. Aus diesem Grund, schließen wir uns dem Konsens des ESPGHAN Komitees an und kommen angesichts des Fehlens von Daten bezüglich wichtiger klinischer Langzeit Vorteile durch Präbiotika (z.B. gastrointestinale Infektionen, allergische Erkrankungen) [121], zu dem Schluss dass „keine generelle Empfehlung der Supplementation von Babynahrung mit Präbiotika“ gegeben werden kann. Ob und in welchem Ausmaß zugefütterte Neugeborene von einer mit Bifidobakterien angereicherten mütterlichen Flora profitieren, muss noch untersucht werden. Zukünftige randomisierte multizentrische klinische Studien an einem repräsentativen Kollektiv werden, bei Berücksichtigung funktioneller sowie validierter klinischer Parameter, den Stellenwert der Präbiotika-Supplementation als prophylaktische und gegebenenfalls therapeutische Maßnahme beleuchten

Translating Knowledge of Autism Spectrum Disorders to Action Through Tool Development and Exploration

Translational processes are needed to move research development, methods, and techniques into clinical application. The knowledge to action framework organizes this bench to bedside process through three phases including: research, translation, and institutionalization without being specific to one disease or condition. The overall goal of this research is to bridge gaps in the translational process from assay development to disease detection through a mixed methods approach. A literature review identifies gaps associated with intestinal permeability and autism spectrum disorders. Mining social media related to autism and GI symptoms captures self-reported or observed data, identifies patterns and themes within the data, and works to translate that knowledge into healthcare applications. Development of novel tests can then examine relationships between zonulin levels, haptoglobin genotype, and autism spectrum disorders, and propose a paradigm shift in the use of proteomics and genomic diagnostic testing from clinical diagnosis to pre-symptomatic testing. Although results from this study do not find statistically significant relationships between zonulin and autism spectrum disorders, they do suggest clinical significance and the need to conduct larger studies. The discovery presents a novel approach for measuring intestinal permeability. Qualitative and quantitative methods collaboratively point toward implementation of molecular and data mining techniques in the development and evaluation of early diagnostic tests and interventions. Equally, the two methods working together drive the field forward in design and development to strengthen the outcomes

Implications of Probiotics on the Maternal-Neonatal Interface: Gut Microbiota, Immunomodulation, and Autoimmunity

Probiotics are being investigated for the treatment of autoimmune disease by re-balancing dysbiosis induced changes in the immune system. Pregnancy is a health concern surrounding autoimmune disease, both for the mother and her child. Probiotics for maternity are emerging on the market and have gained significant momentum in the literature. Thus far, evidence supports that probiotics alter the structure of the normal microbiota and the microbiota changes significantly during pregnancy. The interaction between probiotics-induced changes and normal changes during pregnancy is poorly understood. Furthermore, there is emerging evidence that the maternal gut microbiota influences the microbiota of offspring, leading to questions on how maternal probiotics may influence the health of neonates. Underpinning the development and balance of the immune system, the microbiota, especially that of the gut, is significantly important, and dysbiosis is an agent of immune dysregulation and autoimmunity. However, few studies exist on the implications of maternal probiotics for the outcome of pregnancy in autoimmune disease. Is it helpful or harmful for mother with autoimmune disease to take probiotics, and would this be protective or pathogenic for her child? Controversy surrounds whether probiotics administered maternally or during infancy are healthful for allergic disease, and their use for autoimmunity is relatively unexplored. This review aims to discuss the use of maternal probiotics in health and autoimmune disease and to investigate their immunomodulatory properties

Energy Demands of Early Life Drive a Disease Tolerant Phenotype and Dictate Outcome in Neonatal Bacterial Sepsis

Bacterial sepsis is one of the leading causes of death in newborns. In the face of growing antibiotic resistance, it is crucial to understand the pathology behind the disease in order to develop effective interventions. Neonatal susceptibility to sepsis can no longer be attributed to simple immune immaturity in the face of mounting evidence that the neonatal immune system is tightly regulated and well controlled. The neonatal immune response is consistent with a “disease tolerance” defense strategy (minimizing harm from immunopathology) whereas adults tend toward a “disease resistance” strategy (minimizing harm from pathogens). One major advantage of disease tolerance is that is less energetically demanding than disease resistance, consistent with the energetic limitations of early life. Immune effector cells enacting disease resistance responses switch to aerobic glycolysis upon TLR stimulation and require steady glycolytic flux to maintain the inflammatory phenotype. Rapid and intense upregulation of glucose uptake by immune cells necessitates an increased reliance on fatty acid metabolism to (a) fuel vital tissue function and (b) produce immunoregulatory intermediates which help control the magnitude of inflammation. Increasing disease resistance requires more energy: while adults have fat and protein stores to catabolize, neonates must reallocate resources away from critical growth and development. This understanding of sepsis pathology helps to explain many of the differences between neonatal and adult immune responses. Taking into account the central role of metabolism in the host response to infection and the severe metabolic demands of early life, it emerges that the striking clinical susceptibility to bacterial infection of the newborn is at its core a problem of metabolism. The evidence supporting this novel hypothesis, which has profound implications for interventions, is presented in this review