Sensitivity of the intestinal microflora of patients to antimicrobial preparations studied in order to conduct rational antibiotic treatment

The oral administration of amikacin, ampiox, nystatin to CBA mice and the external treatment of the animals with 1% chlorhexidine solution makes it possible to create the germ-free state in the animals which must be then kept in a sterile box. If such animals receive the decantate of the patient's feces, introduced in a single administration, the microflora, which is subsequently formed in the intestine of the recipient animals, is identical to the donor's microflora. This permits the rapid and accurate determination of the sensitivity of the patient's intestinal microflora to different antimicrobial preparations and their combinations. The antibacterial preparations, effectively suppressing the patient's intestinal anaerobic opportunistic microflora in the intestine of the recipient mice, produce, if subsequently prescribed for treatment, a pronounced corrective effect on such microflora in the patient's intestine.     

A new approach to selecting antibacterial preparations for treating patients with chronic urological infections

The oral administration of microflora, isolated from the urinary tract or feces of urological patients, into the abacterial digestive tract of mice kept under the conditions of germ-free environment leads to the formation of the donors' microflora in the intestine of the recipient animals. Such recipient mice can be used as models for the rapid and highly reliable determination of the sensitivity of microflora in the patient's intestine and urinary tract to different antimicrobial preparations. In different patients such microflora, though similar in its qualitative and quantitative composition, differs in sensitivity to different antimicrobial preparations and their combinations. For the effective treatment of patients with chronic urinary tract infections a preliminary in vivo determination of the sensitivity of intestinal and urinary microflora to different combinations of antimicrobial preparations, carried out with the use of germ-free techniques, is necessary.     

Intestinal microbial patterns of the common marmoset and rhesus macaque

The intestinal microflora of common marmosets and rhesus monkeys were compared by enumerating bacteria from the small and large intestines. Rhesus monkeys had a consistent microflora pattern manifest by higher concentrations of total and Gram-negative aerobic and facultatively anaerobic bacteria, as well as aerobic and anaerobic Lactobacilli, in the large intestine as compared to the small intestine. In contrast, the marmoset microflora were considerably more variable. Approximately two-thirds of the marmosets (designated group A) had an overall profile that resembled the rhesus monkeys, but they had significantly higher concentrations of Gram-negative microflora in their large intestines than the rhesus monkeys. The remaining marmosets (group B) had higher concentrations of bacteria in the small intestine as compared to the large intestine, with the large intestinal concentrations being significantly lower than in the rhesus monkeys and group A marmosets. Moreover, the marmosets did not have detectable levels of aerobic Lactobacilli, and anaerobic Lactobacilli concentrations were significantly lower than in the rhesus macaques. Although it is unknown why microflora differ across species, it is likely that evolutionary adaptations in anatomy and functioning of the gastrointestinal tract influence the concentration and types of bacteria residing as the normal intestinal microflora.     

Immunochemotherapy of infants in the first year of life with intestinal infections due to opportunistic gram-negative aerobic bacteria]

The clinical and microbiological observations of 50 babies of the 1st year of age with intestinal infections due to opportunistic organisms were made. The babies were treated with antibacterial drugs and an immunoglobulin preparation. It was shown that the combined use of antibacterial and immunological preparations in the treatment of the babies with the intestinal infections caused by opportunistic organisms provided their earlier clinical recovery and lowered the unfavourable effect of the antibacterial drugs on the intestinal microflora.     

Invasive Escherichia coli of the O139:K serogroup

The results obtained in the study of the main biological properties of 9 E. coli strains, serogroup O139:K., isolated from monkeys at the Sukhumi monkey breeding colony and yielding the positive result in Sereny's keratoconjunctival test are presented. For the first time E. coli of serovar O139:K.:431 were isolated; these organisms differed from reference strain O139K82:H1 in their enzymatic activity, in the partial composition of O-antigen and in their capacity for inducing experimental keratoconjunctivitis. The isolation of the above-mentioned cultures from monkeys with diagnosed acute intestinal diseases of unclear etiology, both during the life of the animals and in the process of autopsy, from a monkey having had contacts with sick animals in the focus of clinical dysentery, and from monkey subjected to prophylactic examination, as well as the pathogenicity of these strains for guinea pigs, evaluated on the keratoconjunctivitis model, suggest their probable etiological role in E. coli infection in primates and make it possible to regard them as the invasive variants of E. coli, serogroup O139:K..     

黄瓜香等山野菜对糖尿病大鼠脂质代谢及肠道正常菌群的影响

目的观察黄瓜香等对糖尿病大鼠脂质代谢的影响,并进一步探讨其调脂机制。方法选取糖尿病大鼠灌胃给予黄瓜香提取液120mg/（kg.d）,共8周,检测其空腹血脂变化,及其肠道菌群变化。结果（1）经黄瓜香提取物治疗后,治疗组较糖尿病组,甘油三脂、低密度脂蛋白和胆固醇明显降低（P〈0.01）;（2）糖尿病组肠道菌群较正常组有明显变化（P〈0.01）,尤其双歧杆菌、乳杆菌等明显减少,而治疗后肠道菌群得到调整。结论黄瓜香提取物可能通过扶植肠道菌群生长繁殖,对脂质代谢发挥作用,从而达到其调脂目的。     

Nestmate recognition mediated by intestinal bacteria in a termite, Reticulitermes speratus

Discrimination and aggressive responses toward non-nestmates have been observed in a number of termite species, but the mechanism is poorly understood. Here I present the novel hypothesis that differential intestinal bacteria composition leads to production of colony-specific chemical cues that enable nestmate recognition.
The intestinal microflora of a lower termite, Reticulitermes speratus , consisted of many bacteria species. The composition of the intestinal bacteria was exclusively colony-specific. Termites that had adsorbed an unfamiliar odor of bacteria sampled from another colony were fiercely attacked by nestmates. Experimental manipulation of the composition of bacteria by antibiotics successfully changed the recognition behavior toward nestmates. These results indicate that intestinal bacteria play an important role in nestmate recognition.     

Analysis of the hydrogenotrophic microbiota of wild and captive black howler monkeys (Alouatta pigra) in palenque national park, Mexico

Intestinal methanogenesis is one of the major pathways for consumption of hydrogen produced by bacterial fermentation and is considered to affect the efficiency of host energy harvest; however, little information is available regarding the hydrogenotrophic pathways of nonhuman primates in the wild, in general, and of howler monkeys, in particular. Microbial fermentation of plant structural carbohydrates is an important feature in wild howlers owing to the high fiber and low available energy content of leaves, which make up the primary component of their diet. In contrast, captive howlers may consume greater quantities of fruits and vegetables that are higher in water, lower in fiber, and, along with commercial monkey chow commonly added to captive monkey diets, more readily digestible than the natural diet. In this study, we analyzed the composition of methanogens and sulfate-reducing bacteria (SRB) from fecal samples of black howler monkeys (Alouatta pigra) in the wild and in captivity. The hydrogenotrophic microbiota of three groups of monkeys was evaluated by PCR-denaturing gradient gel electrophoresis (DGGE) fingerprinting, small clone library construction, and quantitative real-time PCR. Abundance of methanogens was lower than SRB in all howler monkey groups studied. DGGE banding patterns were highly similar within each wild and captive group but distinct among groups. Desulfovibrionales-enriched DGGE showed reduced microbial diversity in the captive animals compared with their wild counterparts. Taken together, the data demonstrate that environmental or dietary changes of the host imposed by captivity likely influence the composition of intestinal hydrogenotrophs in black howler monkeys.     

Therapeutic Helminth Infection of Macaques with Idiopathic Chronic Diarrhea Alters the Inflammatory Signature and Mucosal Microbiota of the Colon

Idiopathic chronic diarrhea (ICD) is a leading cause of morbidity amongst rhesus monkeys kept in captivity. Here, we show that exposure of affected animals to the whipworm Trichuris trichiura led to clinical improvement in fecal consistency, accompanied by weight gain, in four out of the five treated monkeys. By flow cytometry analysis of pinch biopsies collected during colonoscopies before and after treatment, we found an induction of a mucosal T_H2 response following helminth treatment that was associated with a decrease in activated CD4⁺ Ki67+ cells. In parallel, expression profiling with oligonucleotide microarrays and real-time PCR analysis revealed reductions in T_H1-type inflammatory gene expression and increased expression of genes associated with IgE signaling, mast cell activation, eosinophil recruitment, alternative activation of macrophages, and worm expulsion. By quantifying bacterial 16S rRNA in pinch biopsies using real-time PCR analysis, we found reduced bacterial attachment to the intestinal mucosa post-treatment. Finally, deep sequencing of bacterial 16S rRNA revealed changes to the composition of microbial communities attached to the intestinal mucosa following helminth treatment. Thus, the genus Streptophyta of the phylum Cyanobacteria was vastly increased in abundance in three out of five ICD monkeys relative to healthy controls, but was reduced to control levels post-treatment; by contrast, the phylum Tenericutes was expanded post-treatment. These findings suggest that helminth treatment in primates can ameliorate colitis by restoring mucosal barrier functions and reducing overall bacterial attachment, and also by altering the communities of attached bacteria. These results also define ICD in monkeys as a tractable preclinical model for ulcerative colitis in which these effects can be further investigated.     

Systemic 1-methyl,4-phenyl,1-2-3-6-tetrahydropyridine (MPTP) administration decreases retinal dopamine content in primates

Following MPTP administration, 4 Cynomolgus monkeys developed a parkinsonian syndrome, accompanied by specific changes of both pattern visual evoked potential and electroretinogram. Retinal dopamine and dihydroxyphenylacetic acid contents were measured in the 4 MPTP-treated monkeys and in 3 normal monkeys. Dopamine and dihydroxyphenylacetic acid levels were significantly lower in the retinas of the MPTP-treated animals (p less than 0.001), suggesting that dopamine has a specific function in the visual system of primates.     

Dysbacteriosis and preparations with probiotic function

Information on intestinal microecological disturbances (dysbacteriosis) and the preparations of probiotics, prebiotics and synbiotics used for the correction of resident normal colon microflora is presented. Probiotics are preparations containing live microbes or substances of microbial origin that, when introduced by natural methods are expected to confer beneficial physiologic, biochemical and immune effects to the host through the stabilization and the optimization of functions of normal microflora. Prebiotics are preparations containing a non-digestible food ingredient that beneficially affect the host by selectively stimulating the growth and the activity of a limited number of resident bacteria of normal microflora in the colon. Synbiotics are preparations obtained as the result of the rational combination of probiotics and prebiotics.     

Morphological and ultrastructural characteristics of symbiotic bacteria colonizing the surface of the helminth Triaenophorus nodulosus and the intestine of pike Esox lucius

The microflora inhabiting the intestinal mucosa of the pike and the tegument surface of the intestinal parasite Triaenophorus nodulosus is investigated. By means of electron microscopy, the ultrastructural features of bacteria and pattern of their interaction with the colonized surfaces are estimated. Specific distribution of microorganisms belonging to different morphotypes and subdivided into subpopulations on the colonized surfaces is found. Predominance of gram-negative bacteria in all studied microbiocenoses and abundance of nanobacteria in the “superficial” subpopulations are observed. The bacteria of “a deep population” associated with the basal parts of microtrichiae and microvilli are described. It is concluded that the helminthes, the fish parasites possess the normal microflora characterized by specific composition, by ultrastructural features of cells, and by patterns of interaction with the helminth surface. The obtained data characterize the mechanisms of symbiotic interaction of prokaryotes and eukaryotes in the system parasite-host-symbiotic microflora.     

Mice and Monkeys as Assay Animals for Clostridium perfringens Food Poisoning

Spores and vegetative cells of Clostridium perfringens, in combination with meat or starch paste, sterile culture filtrates, lecithinase, and phosphorylcholine, were administered to mice and rhesus monkeys in an attempt both to evaluate the animals as test agents and, if possible, to elucidate the active factors producing food-poisoning symptoms caused by this organsim. Some of the preparations were administered to the monkeys by stomach tube; others, in gelatin capsules which were treated with formaldehyde so that the release of their contents was delayed and presumably reached the intestines of the animals. Any changes in intestinal passage times and in consistency of stools of the animals were observed, and the counts of C. perfringens in the feces of the monkeys previous and subsequent to treatment were recorded. The results obtained were inconclusive. Diarrhea occurred only relatively infrequently in both species, regardless of the substance fed or the mode of administration. The changes in intestinal passage times were not great, although in the monkeys there appeared to be a slight trend toward reduction as the magnitude of the bacterial load increased. Phosphorylcholine appeared to have little, if any, effect in reducing intestinal passage time of mice or monkeys. No procedures explored in these experiments could be said to be satisfactory as a means of animal assay for food poisoning strains of C. perfringens since typical symptoms did not appear with regularity.     

The experimental and clinical effect of ciprofloxacin on the microflora of the gastrointestinal tract

The study of the influence of cyprofloxacin on the microflora of the gastrointestinal tract has been made under experimental and clinical conditions. As revealed in this study, cyprofloxacin produces a corrective effect on the intestinal microflora; the action of this preparation, in contrast to that of other antimicrobial preparations, is retained for a long time. In patients having duodenal ulcer with bacteriosis caused by Campylobacter pylori and with intestinal dysbacteriosis the combination of cyprofloxacin and cimetidine yields a higher therapeutic effect than the use of cimetidine alone.     

Species composition of intestinal lactoflora of healthy rhesus monkeys

The results of the study of the species composition of the fecal microflora of 15 healthy rhesus macaques, from whom 204 strains of lactobacilli have been isolated and identified, are presented. The intestinal microflora has been shown to include different species, subspecies and biovars of homo- and heterofermentative lactobacilli and to possess definite individual properties. L. acidophilus, mannose-negative biovar I, and L. fermentum, mannose-negative biovars I and II, occur most frequently in feces. Certain differences in the species composition of lactoflora in monkeys and humans have been revealed: in the former, L. fermentum, mannitose-positive biovar III, and L. casei occur considerably more seldom. The inclusion of L. acidophilus strain I L. fermentum strains I and II isolated from rhesus macaques into eubiotics for these monkeys has been suggested.     

The effect of new antimicrobial preparations used in combination with complete gnotobiotic isolation on the survivability and intestinal microflora of total-body irradiated mice

The aim of these investigations was the study of the effect of different antimicrobial preparations on the survival rate and intestinal microflora of mice with experimental acute radiation sickness. These investigations revealed that the survival rate of the animals increased 3.1 times with the use of Supramycin, 2.4 times with the use of Tacef and 1.6 times with the use of Spizef and Pen-bristol. The study of the influence of these preparations on the intestinal microflora revealed that Spizef not only decreased the number of opportunistic microorganisms, but also led to a sharp drop in the level of lactobacteria. The use of Pen-bristol and Tacef led to practically complete elimination of enterobacteria enterococci, staphylococci, as well as lactobacteria. Supramycin essentially suppressed the number of opportunistic microorganisms and did not affect the level of lactobacteria. This was probably the cause of the highest effectiveness of Supramycin in comparison with Tacef, Spizef and Pen-bristol.     

The normal faecal microflora does not affect the adhesion of probiotic bacteria in vitro

Adhesion of probiotic microorganisms to the intestinal mucosa is considered important for many of the reported health effects. The influence of the endogenous microflora on the adhesion of four probiotic lactobacilli to immobilised intestinal mucus was investigated. It was observed that pre-treatment of the immobilised mucus with faecal extract slightly increased the adhesion of Lactobacillus GG. Pre-treatment of the immobilised mucus with faecal bacteria did not affect the adhesion of the tested strains. These results suggest that the normal microflora may not greatly affect the initial adhesion of the probiotic bacteria. This validates the results of earlier reports where the influence of the normal microflora was not taken into account.     

Mono-association of mice with non-cultivable,intestinal, segmented,filamentous bacteria

A technique is described so that mice mono-associated with non-cultivable, segmented filamentous bacteria (SFB's) can be produced for the first time. As SFB donors, mice were used which had an intestinal microflora consisting of both SFB's and bacteria of the genus Clostridium. Recipients were germ-free mice. It was demonstrated that the intraileal inoculation method was more effective than the orogastric route. Therefore, intestinal homogenates of donor mice were treated with filtered ethanol, diluted and administered intraileally to recipient mice. Evidence is presented that cage mates of the recipient mice were mono-associated with SFB's. The availability of these animals, i.e. in vivo monocultures of SFB's, allows taxonomic and functional characterization of SFB's, which was as yet not possible.Abbreviation SFB Segmented filamentous bacterium     

The calcium endocrine system of adolescent rhesus monkeys and controls before and after spaceflight

The calcium endocrine system of nonhuman primates can be influenced by chairing for safety and the weightless environment of spaceflight. The serum of two rhesus monkeys flown on the Bion 11 mission was assayed pre- and postflight for vitamin D metabolites, parathyroid hormone, calcitonin, parameters of calcium homeostasis, cortisol, and indexes of renal function. Results were compared with the same measures from five monkeys before and after chairing for a flight simulation study. Concentrations of 1,25-dihydroxyvitamin D were 72% lower after the flight than before, and more than after chairing on the ground (57%, P < 0.05). Decreases in parathyroid hormone did not reach significance. Calcitonin showed modest decreases postflight (P < 0.02). Overall, effects of spaceflight on the calcium endocrine system were similar to the effects of chairing on the ground, but were more pronounced. Reduced intestinal calcium absorption, losses in body weight, increases in cortisol, and higher postflight blood urea nitrogen were the changes in flight monkeys that distinguished them from the flight simulation study animals.     

Delayed cutaneous hypersensitivity response in tetanus toxoid sensitized rhesus monkeys: predictor of anergy and value in tuberculin skin testing

The primary problem in using the tuberculin skin test in nonhuman primates is the clinical uncertainty concerning the animal's ability to elicit a delayed cutaneous hypersensitivity response. A negative tuberculin skin test can only be meaningful if the animal can produce a delayed cutaneous hypersensitivity reaction. Veterinarians deliberately sensitize animals to antigens in the form of prophylactic vaccination. Therefore, if nonhuman primates were deliberately sensitized to an antigen capable of producing a hypersensitivity response, that antigen should serve as a positive control for delayed cutaneous hypersensitivity reactions. Tetanus toxoid was chosen because repeated immunizations with this antigen is recommended routine medical practice for nonhuman primates housed outdoors. Twenty juvenile, male rhesus (Macaca mulatta) monkeys were selected for this study. The monkeys were assigned randomly to one of two groups of ten animals. The test group was vaccinated with tetanus toxoid intramuscularly at 1 month intervals for a total of three vaccinations. The control group was treated the same except saline was administered rather than tetanus toxoid. Following sensitization, the two groups of animals were challenged with tetanus toxoid intradermally. Eight of the ten monkeys in the test group responded to the tetanus toxoid while none of the control groups responded to the tetanus toxoid. Elicitation of a delayed cutaneous response in animals sensitized to tetanus antigen before challenge may serve as a positive control for delayed cutaneous hypersensitivity. This simple test may serve as a useful adjunct in making objective clinical decisions concerning anergy-suspect animals.